US20030190644A1

US20030190644A1 - Methods for generating databases and databases for identifying polymorphic genetic markers

Info

Publication number: US20030190644A1
Application number: US10/272,756
Authority: US
Inventors: Andreas Braun; Yip Ping
Original assignee: Sequenom Inc
Current assignee: Sequenom Inc
Priority date: 1999-10-13
Filing date: 2002-10-15
Publication date: 2003-10-09
Also published as: US8818735B2; US20100292930A1; US20030180748A1; US20150005194A1; US8229677B2; US20120301882A1; US7668658B2; US20030180749A1; US7332275B2

Abstract

A high throughput method of determining frequencies of genetic variations is provided. The method includes steps of selecting a healthy target population and a genetic variation to be assessed; pooling a plurality of samples of biopolymers obtained from members of the population; determining or detecting the biopolymer that comprises the variation by mass spectrometry; obtaining a mass spectrum or a digital representation thereof; and determining the frequency of the variation in the population.

Description

RELATED APPLICATIONS

This application is a divisional application of copending U.S. patent application Ser. No. 09/687,483, filed Oct. 13, 2000, to Andreas Braun, Hubert Koster, Dirk Van den Boom, Yip Ping, Charles Rodi, Liyan He, Norman Chiu and Christian Jurinke entitled “METHODS FOR GENERATING DATABASES AND DATABASES FOR IDENTIFYING POLYMORPHIC GENETIC MARKERS.”[0001]
Benefit of priority under 35 U.S.C. § 119(e) to the following provisional applications is claimed herein: [0002]
U.S. provisional application Serial No. 60/217,658 to Andreas Braun, Hubert Koster; Dirk Van den Boom, filed Jul. 10, 2000, entitled “METHODS FOR GENERATING DATABASES AND DATABASES FOR IDENTIFYING POLYMORPHIC GENETIC MARKERS”; U.S. provisional application Serial No. 60/159,176 to Andreas Braun, Hubert Koster, Dirk Van den Boom, filed Oct. 13, 1999, entitled “METHODS FOR GENERATING DATABASES AND DATABASES FOR IDENTIFYING POLYMORPHIC GENETIC MARKERS”; U.S. provisional application Serial No. 60/217,251, filed Jul. 10, 2000, to Andreas Braun, entitled “POLYMORPHIC KINASE ANCHOR PROTEIN GENE SEQUENCES, POLYMORPHIC KINASE ANCHOR PROTEINS AND METHODS OF DETECTING POLYMORPHIC KINASE ANCHOR PROTEINS AND NUCLEIC ACIDS ENCODING THE SAME”. This application is also a continuation-in-part of U.S. application Ser. No. 09/663,968, to Ping Yip, filed Sep. 19, 2000, entitled “METHOD AND DEVICE FOR IDENTIFYING A BIOLOGICAL SAMPLE.”[0003]
The above-noted applications and provisional applications are incorporated by reference in their entirety. [0004]

FIELD OF THE INVENTION

Process and methods for creating a database of genomic samples from healthy human donors. Methods that use the database to identify and correlate with polymorphic genetic markers and other markers with diseases and conditions are provided.

BACKGROUND

Diseases in all organisms have a genetic component, whether inherited or resulting from the body's response to environmental stresses, such as viruses and toxins. The ultimate goal of ongoing genomic research is to use this information to develop new ways to identify, treat and potentially cure these diseases. The first step has been to screen disease tissue and identify genomic changes at the level of individual samples. The identification of these “disease” markers has then fueled the development and commercialization of diagnostic tests that detect these errant genes or polymorphisms. With the increasing numbers of genetic markers, including single nucleotide polymorphisms (SNPs), microsatellites, tandem repeats, newly mapped introns and exons, the challenge to the medical and pharmaceutical communities is to identify genotypes which not only identify the disease but also follow the progression of the disease and are predictive of an organism's response to treatment.

Currently the pharmaceutical and biotechnology industries find a disease and then attempt to determine the genomic basis for the disease. This approach is time consuming and expensive and in many cases involves the investigator guessing as to what pathways might be involved in the disease.

Genomics

Presently the two main strategies employed in analyzing the available genomic information are the technology driven reverse genetics brute force strategy and the knowledge-based pathway oriented forward genetics strategy. The brute force approach yields large databases of sequence information but little information about the medical or other uses of the sequence information. Hence this strategy yields intangible products of questionable value. The knowledge-based strategy yields small databases that contain a lot of information about medical uses of particular DNA sequences and other products in the pathway and yield tangible products with a high value.

Polymorphisms

Polymorphisms have been known since 1901 with the identification of blood types. In the 1950's they were identified on the level of proteins using large population genetic studies. In the 1980's and 1990's many of the known protein polymorphisms were correlated with genetic loci on genomic DNA. For example, the gene dose of the apolipoprotein E type 4 allele was correlated with the risk of Alzheimer's disease in late onset families (see, e.g., Corder et al. (1993) Science 261: 921-923; mutation in blood coagulation factor V was associated with resistance to activated protein C (see, e.g., Bertina et aL. (1994) Nature 369:64-67); resistance to HIV-1 infection has been shown in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene (see, e.g., Samson et al. (1996) Nature 382:722-725); and a hypermutable tract in antigen presenting cells (APC, such as macrophages), has been identified in familial colorectal cancer in individuals of Ashkenzi jewish background (see, e.g., Laken et al. (1997) Nature Genet. 17:79-83). There can be more than three million polymorphic sites in the human genome. Many have been identified, but not yet characterized or mapped or associated with a marker.

Single Nucleotide Polymorphisms (SNPs)

Much of the focus of genomics has been in the identification of SNPs, which are important for a variety of reasons. They allow indirect testing (association of haplotypes) and direct testing (functional variants). They are the most abundant and stable genetic markers. Common diseases are best explained by common genetic alterations, and the natural variation in the human population aids in understanding disease, therapy and environmental interactions.

Currently, the only available method to identify SNPs in DNA is by sequencing, which is expensive, difficult and laborious. Furthermore, once a SNP is discovered it must be validated to determine if it is a real polymorphism and not a sequencing error. Also, discovered SNPs must then be evaluated to determine if they are associated with a particular phenotype. Thus, there is a need to develop new paradigms for identifying the genomic basis for disease and markers thereof. Therefore, it is an object herein to provide methods for identifying the genomic basis of disease and markers thereof.

SUMMARY

Databases and methods using the databases are provided herein. The databases comprise sets of parameters associated with subjects in populations selected only on the basis of being healthy (i e., where the subjects are mammals, such as humans, they are selected based upon apparent health and no detectable infections). The databases can be sorted based upon one or more of the selected parameters.

The databases, for example, can be relational databases, in which an index that represents each subject serves to relate parameters, which are the data, such as age, ethnicity, sex, medical history, etc. and ultimately genotypic information, that was inputted into and stored in the database. The database can then be sorted according to these parameters. Initially, the parameter information is obtained from a questionnaire answered by each subject from whom a body tissue or body fluid sample is obtained. As additional information about each sample is obtained, this information can be entered into the database and can serve as a sorting parameter.

The databases obtained from healthy individuals have numerous uses, such as correlating known polymorphisms with a phenotype or disease. The databases can be used to identify alleles that are deleterious, that are beneficial, and that are correlated with diseases.

For purposes herein, genotypic information can be obtained by any method known to those of skill in the art, but is generally obtained using mass spectrometry.

Also provided herein, is a new use for existing databases of subjects and genotypic and other parameters, such as age, ethnicity, race, and gender. Any database can be sorted according to the methods herein, and alleles that exhibit statistically significant correlations with any of the sorting parameters can be identified. It is noted, however, is noted, that the databases provided herein and randomly selected databases will perform better in these methods, since disease-based databases suffer numerous limitations, including their relatively small size, the homogeneity of the selected disease population, and the masking effect of the polymorphism associated with the markers for which the database was selected. Hence, the healthy database provided herein, provides advantages not heretofore recognized or exploited. The methods provided herein can be used with a selected database, including disease-based databases, with or without sorting for the discovery and correlation of polymorphisms. In addition, the databases provided herein represent a greater genetic diversity than the unselected databases typically utilized for the discovery of polymorphisms and thus allow for the enhanced discovery and correlation of polymorphisms.

The databases provided herein can be used for taking an identified polymorphism and ascertaining whether it changes in frequency when the data are sorted according to a selected parameter.

One use of these methods is correlating a selected marker with a particular parameter by following the occurrence of known genetic markers and then, having made this correlation, determining or identifying correlations with diseases. Examples of this use are p53 and Lipoprotein Lipase polymorphism. As exemplified herein, known markers are shown to have particular correlation with certain groups, such as a particular ethnicity or race or one sex. Such correlations will then permit development of better diagnostic tests and treatment regimens.

These methods are valuable for identifying one or more genetic markers whose frequency changes within the population as a function of age, ethnic group, sex or some other criteria. This can allow the identification of previously unknown polymorphisms and ultimately a gene or pathway involved in the onset and progression of disease.

The databases and methods provided herein permit, among other things, identification of components, particularly key components, of a disease process by understanding its genetic underpinnings and also permit an understanding of processes, such as individual drug responses. The databases and methods provided herein also can be used in methods involving elucidation of pathological pathways, in developing new diagnostic assays, identifying new potential drug targets, and in identifying new drug candidates.

The methods and databases can be used with experimental procedures, including, but are not limited to, in silico SNP identification, in vitro SNP identification/verification, genetic profiling of large populations, and in biostatistical analyses and interpretations.

Also provided herein, are combinations that contain a database provided herein and a biological sample from a subject in the database, and typically biological samples from all subjects or a plurality of subjects in the database. Collections of the tissue and body fluid samples are also provided.

Also, provided herein, are methods for determining a genetic marker that correlates with age, comprising identifying a polymorphism and determining the frequency of the polymorphism with increasing age in a healthy population.

Further provided herein are methods for determining whether a genetic marker correlates with susceptibility to morbidity, early mortality, or morbidity and early mortality, comprising identifying a polymorphism and determining the frequency of the polymorphism with increasing age in a healthy population.

Any of the methods herein described can be used out in a multiplex format.

Also provided are an apparatus and process for accurately identifying genetic information. It is another object herein that genetic information be extracted from genetic data in a highly automated manner. Therefore, to overcome the deficiencies in the known conventional systems, methods and apparatus for identifying a biological sample are provided.

Briefly, the method and system for identifying a biological sample generates a data set indicative of the composition of the biological sample. In a particular example, the data set is DNA spectrometry data received from a mass spectrometer. The data set is denoised, and a baseline is deleted. Since possible compositions of the biological sample can be known, expected peak areas can be determined. Using the expected peak areas, a residual baseline is generated to further correct the data set. Probable peaks are then identifiable in the corrected data set, which are used to identify the composition of the biological sample. In a disclosed example, statistical methods are employed to determine the probability that a probable peak is an actual peak, not an actual peak, or that the data too inconclusive to call.

Advantageously, the method and system for identifying a biological sample accurately makes composition calls in a highly automated manner. In such a manner, complete SNP profile information, for example, can be collected efficiently. More importantly, the collected data are analyzed with highly accurate results. For example, when a particular composition is called, the result can be relied upon with great confidence. Such confidence is provided by the robust computational process employed

DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts an exemplary sample bank. [0032] Panel 1 shows the samples as a function of sex and ethnicity. Panel 2 shows the Caucasians as a function of age. Panel 3 shows the Hispanics as a function of age.
FIGS. 2A and 2C show an age- and sex-distribution of the 291S allele of the lipoprotein lipase gene in which a total of 436 males and 589 females were investigated. FIG. 2B shows an age distribution for the 436 males. [0033]
FIG. 3 is an exemplary questionnaire for population-based sample banking. [0034]
FIG. 4 depicts processing and tracking of blood sample components. [0035]
FIG. 5 depicts the allelic frequency of “sick” alleles and “healthy” alleles as a function of age. It is noted that the relative frequency of healthy alleles increases in a population with increasing age. [0036]
FIG. 6 depicts the age-dependent distribution of ApoE genotypes (see, Schächter et al. (1994) [0037] Nature Genetics 6:29-32).
FIG. 7A-D depicts age-related and genotype frequency of the p53 (tumor suppressor) [0038] codon 72 among the Caucasian population in the database. *R72 and *P72 represent the frequency of the allele in the database population. R72, R72P, and P72 represent the genotypes of the individuals in the population. The frequency of the homozygous P72 allele drops from 6.7% to 3.7% with age.
FIG. 8 depicts the allele and genotype frequencies of the p21 S31R allele as a function of age. [0039]
FIG. 9 depicts the frequency of the [0040] FVII Allele 353Q in pooled versus individual samples.
FIG. 10 depicts the frequency of the CETP (cholesterol ester transfer protein) allele in pooled versus individual samples. [0041]
FIG. 11 depicts the frequency of the plasminogen activator inhibitor-1 (PAI-1) 5G in pooled versus individual samples. [0042]
FIG. 12 shows mass spectra of the samples and the ethnic diversity of the PAI-1 alleles. [0043]
FIG. 13 shows mass spectra of the samples and the ethnic diversity of the CETP 405 alleles. [0044]
FIG. 14 shows mass spectra of the samples and the ethnic diversity of the Factor VII 353 alleles. [0045]
FIG. 15 shows ethnic diversity of PAI-1, CETP and Factor VII using the pooled DNA samples. [0046]
FIG. 16 shows the p53-Rb pathway and the relationships among the various factors in the pathway. [0047]
FIG. 17, which is a block diagram of a computer constructed to provide and process the databases described herein, depicts a typical computer system for storing and sorting the databases provided herein and practicing the methods provided herein. [0048]
FIG. 18 is a flow diagram that illustrates the processing steps performed using the computer illustrated in FIG. 17, to maintain and provide access to the databases for identifying polymorphic genetic markers. [0049]
FIG. 19 is a histogram showing the allele and genotype distribution in the age and sex stratified Caucasian population for the AKAP10-1 locus. Bright green bars show frequencies in individuals younger than 40 years. Dark green bars show frequencies in individuals older than 60 years. [0050]
FIG. 20 is a histogram showing the allele and genotype distribution in the age and sex stratified Caucasian population for the AKAP10-5 locus. Bright green bars show frequencies in individuals younger than 40 years; dark green bars show frequencies in individuals older than 60 years. [0051]
FIG. 21 is a histogram showing the allele and genotype distribution in the age and sex stratified Caucasian population for the h-msrA locus. Genotype difference between male age groups is significant. Bright green bars show frequencies in individuals younger than 40 years. Dark green bars show frequencies in individuals older than 60 years. [0052]
FIG. 22A-D is a sample data collection questionnaire used for the healthy database. [0053]
FIG. 23 is a flowchart showing processing performed by the computing device of FIG. 24 when performing genotyping of sense strands and antisense strands from assay fragments. [0054]
FIG. 24 is a block diagram showing a system provided herein; [0055]
FIG. 25 is a flowchart of a method of identifying a biological sample provided herein; [0056]
FIG. 26 is a graphical representation of data from a mass spectrometer; [0057]
FIG. 27 is a diagram of wavelet transformation of mass spectrometry data; [0058]
FIG. 28 is a graphical representation of [0059] wavelet stage 0 hi data;
FIG. 29 is a graphical representation of [0060] stage 0 noise profile;
FIG. 30 is a graphical representation of generating stage noise standard deviations; [0061]
FIG. 31 is a graphical representation of applying a threshold to data stages; [0062]
FIG. 32 is a graphical representation of a sparse data set; [0063]
FIG. 33 is a formula for signal shifting; [0064]
FIG. 34 is a graphical representation of a wavelet transformation of a denoised and shifted signal; [0065]
FIG. 35 is a graphical representation of a denoised and shifted signal; [0066]
FIG. 36 is a graphical representation of removing peak sections; [0067]
FIG. 37 is a graphical representation of generating a peak free signal; [0068]
FIG. 38 is a block diagram of a method of generating a baseline correction; [0069]
FIG. 39 is a graphical representation of a baseline and signal; [0070]
FIG. 40 is a graphical representation of a signal with baseline removed; [0071]
FIG. 41 is a table showing compressed data; [0072]
FIG. 42 is a flowchart of method for compressing data; [0073]
FIG. 43 is a graphical representation of mass shifting; [0074]
FIG. 44 is a graphical representation of determining peak width; [0075]
FIG. 45 is a graphical representation of removing peaks; [0076]
FIG. 46 is a graphical representation of a signal with peaks removed; [0077]
FIG. 47 is a graphical representation of a residual baseline; [0078]
FIG. 48 is a graphical representation of a signal with residual baseline removed; [0079]
FIG. 49 is a graphical representation of determining peak height; [0080]
FIG. 50 is a graphical representation of determining signal-to-noise for each peak; [0081]
FIG. 51 is a graphical representation of determining a residual error for each peak; [0082]
FIG. 52 is a graphical representation of peak probabilities; [0083]
FIG. 53 is a graphical representation of applying an allelic ratio to peak probability; [0084]
FIG. 54 is a graphical representation of determining peak probability; [0085]
FIG. 55 is a graphical representation of calling a genotype; [0086]
FIG. 56 is a flowchart showing a statistical procedure for calling a genotype; [0087]
FIG. 57 is a flowchart showing processing performed by the computing device of FIG. 1 when performing standardless genotyping; and [0088]
FIG. 58 is graphical representation of applying an allelic ratio to peak probability for standardless genotype processing.[0089]

DETAILED DESCRIPTION

Definitions [0090]
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this invention belongs. All patents, applications, published applications and other publications and sequences from GenBank and other databases referred to herein throughout the disclosure are incorporated by reference in their entirety. [0091]
As used herein, a biopolymer includes, but is not limited to, nucleic acid, proteins, polysaccharides, lipids and other macromolecules. Nucleic acids include DNA, RNA, and fragments thereof. Nucleic acids can be derived from genomic DNA, RNA, mitochondrial nucleic acid, chloroplast nucleic acid and other organelles with separate genetic material. [0092]
As used herein, morbidity refers to conditions, such as diseases or disorders, that compromise the health and well-being of an organism, such as an animal. Morbidity susceptibility or morbidity-associated genes are genes that, when altered, for example, by a variation in nucleotide sequence, facilitate the expression of a specific disease clinical phenotype. Thus, morbidity susceptibility genes have the potential, upon alteration, of increasing the likelihood or general risk that an organism will develop a specific disease. [0093]
As used herein, mortality refers to the statistical likelihood that an organism, particularly an animal, will not survive a full predicted lifespan. Hence, a trait or a marker, such as a polymorphism, associated with increased mortality is observed at a lower frequency in older than younger segments of a population. [0094]
As used herein, a polymorphism, e.g. genetic variation, refers to a variation in the sequence of a gene in the genome amongst a population, such as allelic variations and other variations that arise or are observed. Thus, a polymorphism refers to the occurrence of two or more genetically determined alternative sequences or alleles in a population. These differences can occur in coding and non-coding portions of the genome, and can be manifested or detected as differences in nucleic acid sequences, gene expression, including, for example transcription, processing, translation, transport, protein processing, trafficking, DNA synthesis, expressed proteins, other gene products or products of biochemical pathways or in post-translational modifications and any other differences manifested amongst members of a population. A single nucleotide polymorphism (SNP) refers to a polymorphism that arises as the result of a single base change, such as an insertion, deletion or change in a base. [0095]
A polymorphic marker or site is the locus at which divergence occurs. Such site can be as small as one base pair (an SNP). Polymorphic markers include, but are not limited to, restriction fragment length polymorphisms, variable number of tandem repeats (VNTR's), hypervariable regions, minisatellites, dinucleotide repeats, trinucleotide repeats, tetranucleotide repeats and other repeating patterns, simple sequence repeats and insertional elements, such as Alu. Polymorphic forms also are manifested as different mendelian alleles for a gene. Polymorphisms can be observed by differences in proteins, protein modifications, RNA expression modification, DNA and RNA methylation, regulatory factors that alter gene expression and DNA replication, and any other manifestation of alterations in genomic nucleic acid or organelle nucleic acids. [0096]
As used herein, a healthy population refers to a population of organisms, including but are not limited to, animals, bacteria, viruses, parasites, plants, eubacteria, and others, that are disease free. The concept of disease-free is a function of the selected organism. For example, for mammals it refers to a subject not manifesting any disease state. Practically a healthy subject, when human, is defined as human donor who passes blood bank criteria to donate blood for eventual use in the general population. These criteria are as follows: free of detectable viral, bacterial, mycoplasma, and parasitic infections; not anemic; and then further selected based upon a questionnaire regarding history (see FIG. 3). Thus, a healthy population represents an unbiased population of sufficient health to donate blood according to blood bank criteria, and not further selected for any disease state. Typically such individuals are not taking any medications. For plants, for example, it is a plant population that does not manifest diseases pathology associated with plants. For bacteria it is a bacterial population replicating without environmental stress, such as selective agents, heat and other pathogens. [0097]
As used herein, a healthy database (or healthy patient database) refers to a database of profiles of subjects that have not been pre-selected for any particular disease. Hence, the subjects that serve as the source of data for the database are selected, according to predetermined criteria, to be healthy. In contrast to other such databases that have been pre-selected for subjects with a particular disease or other characteristic, the subjects for the database provided herein are not so-selected. Also, if the subjects do manifest a disease or other condition, any polymorphism discovered or characterized should be related to an independent disease or condition. In a one embodiment, where the subjects are human, a healthy subject manifests no disease symptoms and meets criteria, such as those set by blood banks for blood donors. [0098]
Thus, the subjects for the database are a population of any organism, including, but are not limited to, animals, plants, bacteria, viruses, parasites and any other organism or entity that has nucleic acid. Among subjects are mammals, such as, although not necessarily, humans. Such a database can capture the diversity of a population, thus providing for discovery of rare polymorphisms. [0099]
As used herein, a profile refers to information relating to, but not limited to and not necessarily including all of, age, sex, ethnicity, disease history, family history, phenotypic characteristics, such as height and weight and other relevant parameters. A sample collect information form is shown in FIG. 22, which illustrates profile intent. [0100]
As used herein, a disease state is a condition or abnormality or disorder that can be inherited or result from environmental stresses, such as toxins, bacterial, fungal and viral infections. [0101]
As used herein, set of non-selected subjects means that the subjects have not been pre-selected to share a common disease or other characteristic. They can be selected to be healthy as defined herein. [0102]
As used herein, a phenotype refers to a set of parameters that includes any distinguishable trait of an organism. A phenotype can be physical traits and can be, in instances in which the subject is an animal, a mental trait, such as emotional traits. Some phenotypes can be determined by observation elicited by questionnaires (see, e.g., FIGS. [0103] 3 and 22) or by referring to prior medical and other records. For purposes herein, a phenotype is a parameter around which the database can be sorted.
As used herein, a parameter is any input data that will serve as a basis for sorting the database. These parameters will include phenotypic traits, medical histories, family histories and any other such information elicited from a subject or observed about the subject. A parameter can describe the subject, some historical or current environmental or social influence experienced by the subject, or a condition or environmental influence on someone related to the subject. Paramaters include, but are not limited to, any of those described herein, and known to those of skill in the art. [0104]
As used herein, haplotype refers to two or polymorphism located on a single DNA strand. Hence, haplotyping refers to identification of two or more polymorphisms on a single DNA strand. Haplotypes can be indicative of a phenotype. For some disorders a single polymorphism can suffice to indicate a trait; for others a plurality (i.e., a haplotype) can be needed. Haplotyping can be performed by isolating nucleic acid and separating the strands. In addition, when using enzymes such a certain nucleases, that produce, different size fragments from each strand, strand separation is not needed for haplotyping. [0105]
As used herein, pattern with reference to a mass spectrum or mass spectrometric analyses, refers to a characteristic distribution and number of signals (such peaks or digital representations thereof). [0106]
As used herein, signal in the context of a mass spectrum and analysis thereof refers to the output data, which the number or relative number of moleucles having a particular mass. Signals include “peaks” and digital representations thereof. [0107]
As used herein, adaptor, when used with reference to haplotyping using Fen ligase, refers to a nucleic acid that specifically hybridizes to a polymorphism of interest. An adaptor can be partially double-stranded. An adaptor complex is formed when an adaptor hybridizes to its target. [0108]
As used herein, a target nucleic acid refers to any nucleic acid of interest in a sample. It can contain one or more nucleotides. [0109]
As used herein, standardless analysis refers to a determination based upon an internal standard. For example, the frequency of a polymorphism can be determined herein by comparing signals within a single mass spectrum. [0110]
As used herein, amplifying refers to methods for increasing the amount of a bipolymer, especially nucleic acids. Based on the 5′ and 3′ primers that are chosen, amplication also serves to restrict and define the region of the genome which is subject to analysis. Amplification can be performed by any method known to those skilled in the art, including use of the polymerase chain reaction (PCR) etc. Amplification, e.g., PCR must be done quantitatively when the frequency of polymorphism is required to be determined. [0111]
As used herein, cleaving refers to non-specific and specific fragmentation of a biopolymer. [0112]
As used herein, multiplexing refers to the simultaneous detection of more than one polymorphism. Methods for performing multiplexed reactions, particularly in conjunction with mass spectrometry are known (see, e.g., U.S. Pat. Nos. 6,043,031, 5,547,835 and International PCT application No. WO 97/37041). [0113]
As used herein, reference to mass spectrometry encompasss any suitable mass spectrometric format known to those of skill in the art. Such formats iniude, but are not limited to, Matrix-Assisted Laser Desorption/Ionization, Time-of-Flight (MALDI-TOF), Electrospray (ES), IR-MALDI (see, e.g., published International PCT application No.99/57318 and U.S. Pat. No. 5,118,937), Ion Cyclotron Resonance (ICR), Fourier Transform and combinations thereof. MALDI, particular UV and IR, are among the formats contemplated. [0114]
As used herein, mass spectrum refers to the presentation of data obtained from analyzing a biopolymer or fragment thereof by mass spectrometry either graphically or encoded numerically. [0115]
As used herein, a blood component is a component that is separated from blood and includes, but is not limited to red blood cells and platelets, blood clotting factors, plasma, enzymes, plasminogen, immunoglobulins. A cellular blood component is a component of blood, such as a red blood cell, that is a cell. A blood protein is a protein that is normally found in blood. Examples of such proteins are blood factors VII and VII. Such proteins and components are well-known to those of skill in the art. [0116]
As used herein, plasma can be prepared by any method known to those of skill in the art. For example, it can be prepared by centrifuging blood at a force that pellets the red cells and forms an interface between the red cells and the buffy coat, which contains leukocytes, above which is the plasma. For example, typical platelet concentrates contain at least about 10% plasma. [0117]
Blood can be separated into its components, including, but not limited to, plasma, platelets and red blood cells by any method known to those of skill in the art. For example, blood can be centrifuged for a sufficient time and at a sufficient acceleration to form a pellet containing the red blood cells. Leukocytes collect primarily at the interface of the pellet and supernatant in the buffy coat region. The supernatant, which contains plasma, platelets, and other blood components, can then be removed and centrifuged at a higher acceleration, whereby the platelets pellet. [0118]
As used herein, p53 is a cell cycle control protein that assesses DNA damage and acts as a transcription factor regulation gene which control cell growth, DNA repair and apoptosis. The p53 mutations have been found in a wide variety of different cancers, including all of the different types of leukemia, with varying frequency. The loss of normal p53 functions results in genomic instability and uncontrolled growth of the host cell. [0119]
As used herein, p21 is a cyclin-dependent kinase inhibitor, associated with G1 phase arrest of normal cells. Expression triggers apoptosis or programmed cell death and has been associated with Wilms' tumor, a pediatric kidney cancer. [0120]
As used herein, Factor VII is a serine protease involved the extrinsic blood coagulation cascade. This factor is activated by thrombin and works with tissue factor (Factor III) in the processing of Factor X to Factor Xa. Evidence has supported an association between polymorphisms in the gene and increase Factor VII activity which can result in an elevated risk of ischemic cardiovascular disease including myocardial infarction. [0121]
As used herein, a relational database stores information in a form representative of matrices, such as two-dimensional tables, including rows and columns of data, or higher dimensional matrices. For example, in one embodiment, the relational database has separate tables each with a parameter. The tables are linked with a record number, which also acts as an index. The database can be searched or sorted by using data in the tables and is stored in any suitable storage medium, such as floppy disk, CD rom disk, hard drive or other suitable medium. [0122]
As used herein, a bar codes refers any array of optically readable marks of any desired size and shape that are arranged in a reference context or frame of, typically, although not necessarily, one or more columns and one or more rows. For purposes herein, the bar code refers to any symbology, not necessary “bar” but can include dots, characters or any symbol or symbols. [0123]
As used herein, symbology refers to an identifier code or symbol, such as a bar code, that is linked to a sample. The index will reference each such symbology. The symbology is any code known or designed by the user. The symbols are associated with information stored in the database. For example, each sample can be uniquely identified with an encoded symbology. The parameters, such as the answers to the questions and subsequent genotypic and other information obtained upon analysis of the samples is included in the database and associated with the symbology. The database is stored on any suitable recording medium, such as a hard drive, a floppy disk, a tape, a CD ROM, a DVD disk and any other suitable medium. [0124]
Databases [0125]
Human genotyping is currently dependent on collaborations with hospitals, tissues banks and research institutions that provide samples of disease tissue. This approach is based on the concept that the onset and/or progression of diseases can be correlated with the presence of a polymorphisms or other genetic markers. This approach does not consider that disease correlated with the presence of specific markers and the absence of specific markers. It is shown herein that identification and scoring of the appearance and disappearance of markers is possible only if these markers are measured in the background of healthy subjects where the onset of disease does not mask the change in polymorphism occurrence. Databases of information from disease populations suffer from small sample size, selection bias and heterogeneity. The databases provided herein from healthy populations solve these problems by permitting large sample bands, simple selection methods and diluted heterogeneity. [0126]
Provided herein are first databases of parameters, associated with non-selected, particularly healthy, subjects. Also provided are combinations of the databases with indexed samples obtained from each of the subjects. Further provided are databases produced from the first databases. These contain, in addition to the original parameters, information, such as genotypic information, including, but are not limited to, genomic sequence information, derived from the samples. [0127]
The databases, which are herein designated healthy databases, are so-designated because they are not obtained from subjects pre-selected for a particular disease. Hence, although individual members can have a disease, the collection of individuals is not selected to have a particular disease. [0128]
The subjects from whom the parameters are obtained comprise either a set of subjects who are randomly selected across, typically, all populations, or are pre-selected to be disease-free or healthy. As a result, the database is not selected to be representative of any pre-selected phenotype, genotype, disease or other characteristic. Typically the number of subjects from which the database is prepared is selected to produce statistically significant results when used in the methods provided herein. Generally, the number of subjects will be greater than 100, 200, and typically than 1000. The precise number can be empirically determined based upon the frequency of the parameter(s) that can be used to sort the database. Generally the population can have at least 50, at least 100, at least 200, at least 500, at least 1000, at least 5000 or at least 10,000 or more subjects. [0129]
Upon identification of a collection of subjects, information about each subject is recorded and associated with each subject as a database. The information associated with each of the subjects, includes, but is not limited to, information related to historical characteristics of the subjects, phenotypic characteristics and also genotypic characteristics, medical characteristics and any other traits and characteristics about the subject that can be determined. This information will serve as the basis for sorting the database. [0130]
In an exemplary embodiment, the subjects are mammals, such as humans, and the information relates to one or more of parameters, such as age, sex, medical history, ethnicity and any other factor. Such information, when the animals are humans, for example, can be obtained by a questionnaire and by observations about the individual, such as hair color, eye color and other characteristics. Genotypic information can be obtained from tissue or other body and body fluid samples from the subject. [0131]
The healthy genomic database can include profiles and polymorphisms from healthy individuals from a library of blood samples where each sample in the library is an individual and separate blood or other tissue sample. Each sample in the database is profiled as to the sex, age, ethnic group, and disease history of the donor. [0132]
The databases are generated by first identifying healthy populations of subjects and obtaining information about each subject that will serve as the sorting parameters for the database. This information can be entered into a storage medium, such as the memory of a computer. [0133]
The information obtained about each subject in a population used for generating the database is stored in a computer memory or other suitable storage medium. The information is linked to an identifier associated with each subject. Hence the database will identify a subject, for example by a datapoint representative of a bar code, and then all information, such as the information from a questionnaire, regarding the individual is associated with the datapoint. As the information is collected the database is generated. [0134]
Thus, for example, profile information, such as subject histories obtained from questionnaires, is collected in the database. The resulting database can be sorted as desired, using standard software, such as by age, sex and/or ethnicity. An exemplary questionnaire for subjects from whom samples are to be obtained is shown in FIGS. [0135] 22A-D. Each questionnaire, for example, can be identified by a bar code, particularly a machine readable bar code for entry into the database. After a subject provides data and is deemed to be healthy (i.e., meets standards for blood donation), the data in the questionnaire is entered into the database and is associated with the bar code. A tissue, cell or blood sample is obtained from the subject.
FIG. 4 exemplifies processing and tracking of blood sample components. Each component is tracked with a bar code, dated, is entered into the database and associated with the subject and the profile of the subject. Typically, the whole blood is centrifuged to produce plasma, red blood cells (which pellet) and leukocytes found in the buffy coat which layers in between. Various samples are obtained and coded with a bar code and stored for use as needed. [0136]
Samples are collected from the subjects. The samples include, but are not limited to, tissues, cells, and fluids, such as nucleic acid, blood, plasma, amniotic fluid, synovial fluid, urine, saliva, aqueous humor, sweat, sperm samples and cerebral spinal fluid. It is understood that the particular set of samples depends upon the organisms in the population. [0137]
Once samples are obtained the collection can be stored and, in some embodiments, each sample is indexed with an identifier, particularly a machine readable code, such as a bar code. For analyses, the samples or components of the samples, particularly biopolymers and small molecules, such as nucleic acids and/or proteins and metabolites, are isolated. [0138]
After samples are analyzed, this information is entered into the database in the memory of the storage medium and associated with each subject. This information includes, but is not limited to, genotypic information. Particularly, nucleic acid sequence information and other information indicative of polymorphisms, such as masses of PCR fragments, peptide fragment sequences or masses, spectra of biopolymers and small molecules and other indicia of the structure or function of a gene, gene product or other marker from which the existence of a polymorphism within the population can be inferred. [0139]
In an exemplary embodiment, a database can be derived from a collection of blood samples. For example, FIG. 1(see, also FIG. 10) shows the status of a collection of over 5000 individual samples. The samples were processed in the laboratory following SOP (standard operating procedure) guidelines. Any standard blood processing protocol can be used. [0140]
For the exemplary database described herein, the following criteria were used to select subjects: [0141]
No testing is done for infectious agents. [0142]
Age: At least 17 years old [0143]
Weight: Minimum of 110 pounds [0144]
Permanently Disqualified: [0145]
History of hepatitis (after age 11) [0146]
Leukemia Lymphoma [0147]
Human immunodeficiency virus (HIV),AIDS [0148]
Chronic kidney disease [0149]
Temporarily Disqualified: [0150]
Pregnancy—until six weeks after delivery, miscarriage or abortion [0151]
Major surgery or transfusions—for one year [0152]
Mononucleosis—until complete recovery [0153]
Prior whole blood donation—for eight weeks [0154]
Antibiotics by injection for one week; by mouth, for forty-eight hours, except antibiotics for skin complexion; [0155]
5 year Deferment: [0156]
Internal cancer and skin cancer if it has been removed, is healed and there is no recurrence [0157]
These correspond to blood bank criteria for donating blood and represent a healthy population as defined herein for a human healthy database. [0158]
5 Structure of the Database [0159]
Any suitable database structure and format known to those of skill in the art can be employed. For example, a relational database is a an exemplary format in which data are stored as matrices or tables of the parameters linked by an indexer that identifies each subject. Software for preparing and manipulating, including sorting the database, can be readily developed or adapted from commercially available software, such as Microsoft Access. [0160]
Quality Control [0161]
Quality control procedures can be implemented. For example, after collection of samples, the quality of the collection in the bank can be assessed. For example, mix-up of samples can be checked by testing for known markers, such as sex. After samples are separated by ethnicity, samples are randomly tested for a marker associated with a particular ethnicity, such as HLA DQA1 group specific component, to assess whether the samples have been properly sorted by ethnic group. An exemplary sample bank is depicted in FIG. 4. [0162]
Obtaining Genotypic Data and Other Parameters for the Database [0163]
After informational and historical parameters are entered into the database, material from samples obtained from each subject, is analyzed. Analyzed material include proteins, metabolites, nucleic acids, lipids and any other desired constituent of the material. For example, nucleic acids, such as genomic DNA, can be analyzed by sequencing. [0164]
Sequencing can be performed using any method known to those of skill in the art. For example, if a polymorphism is identified or known, and it is desired to assess its frequency or presence among the subjects in the database, the region of interest from each sample can be isolated, such as by PCR or restriction fragments, hybridization or other suitable method known to those of skill in the art and sequenced. For purposes herein, sequencing analysis can be effected using mass spectrometry (see, e.g., U.S. Pat. Nos. 5,547,835, 5,622,824, 5,851,765, and 5,928,906). Nucleic acids also can be sequenced by hybridization (see, e.g., U.S. Pat. Nos. 5,503,980, 5,631,134, 5,795,714) and including analysis by mass spectrometry (see, U.S. application Ser. Nos. 08/419,994 and 09/395,409). [0165]
In other detection methods, it is necessary to first amplify prior to identifying the allelic variant. Amplification can be performed, e.g., by PCR and/or LCR, according to methods known in the art. In one embodiment, genomic DNA of a cell is exposed to two PCR primers and amplification for a number of cycles sufficient to produce the required amount of amplified DNA. In some embodiments, the primers are located between 150 and 350 base pairs apart. [0166]
Alternative amplification methods include: self sustained sequence replication (Guatelli, J. C. et al., 1990, Proc. Natl. Acad. Sci. U.S.A. 87:1874-1878), transcriptional amplification system (Kwoh, D. Y. et al., 1989, Proc. Natl. Acad. Sci. U.S.A. 86:1173-1177), Q-Beta Replicase (Lizardi, P. M. et al., 1988, Bio/Technology 6:1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers. [0167]
Nucleic acids also can be analyzed by detection methods and protocols, particularly those that rely on mass spectrometry (see, e.g., U.S. Pat. No. 5,605,798, 6,043,031, allowed copending U.S. application Ser. No. 08/744,481, U.S. application Ser. No. 08/990,851 and International PCT application No. WO 99/31278, International PCT application No. WO 98/20019). These methods can be automated (see, e.g., copending U.S. application Ser. No. 09/285,481 and published International PCT application No. PCT/US00/08111, which describes an automated process line). Among the methods of analysis herein are those involving the primer oligo base extension (PROBE) reaction with mass spectrometry for detection (described herein and elsewhere, see e.g., U.S. Pat. No. 6,043,031; see, also U.S. application Ser. Nos. 09/287,681, 09/287,682, 09/287,141 and 09/287,679, allowed copending U.S. application Ser. No. 08/744,481, International PCT application No. PCT/US97/20444, published as International PCT application No. WO 98/20019, and based upon U.S. application Ser. Nos. 08/744,481, 08/744,590, 08/746,036, 08/746,055, 08/786,988, 08/787,639, 08/933,792, 08/746,055, 08/786,988 and 08/787,639; see, also U.S. application Ser. No. 09/074,936, U.S. Pat. No. 6,024,925, and U.S. application Ser. Nos. 08/746,055 and 08/786,988, and published International PCT application No. WO 98/20020) [0168]
A chip based format in which the biopolymer is linked to a solid support, such as a silicon or silicon-coated substrate, such as in the form of an array, is among the formats for performing the analyses is. Generally, when analyses are performed using mass spectrometry, particularly MALDI, small nanoliter volumes of sample are loaded on, such that the resulting spot is about, or smaller than, the size of the laser spot. It has been found that when this is achieved, the results from the mass spectrometric analysis are quantitative. The area under the signals in the resulting mass spectra are proportional to concentration (when normalized and corrected for background). Methods for preparing and using such chips are described in U.S. Pat. No. 6,024,925, co-pending U.S. application Ser. Nos. 08/786,988, 09/364,774, 09/371,150 and 09/297,575; see, also U.S. application Ser. No. PCT/US97/20195, which published as WO 98/20020. Chips and kits for performing these analyses are commercially available from SEQUENOM under the trademark MassARRAY. MassArray relies on the fidelity of the enzymatic primer extension reactions combined with the miniaturized array and MALDI-TOF (Matrix-Assisted Laser Desorption Ionization-Time of Flight) mass spectrometry to deliver results rapidly. It accurately distinguishes single base changes in the size of DNA fragments associated with genetic variants without tags. [0169]
The methods provided herein permit quantitative determination of alleles. The areas under the signals in the mass spectra can be used for quantitative determinations. The frequency is determined from the ratio of the signal to the total area of all of the spectrum and corrected for background. This is possible because of the PROBE technology as described in the above applications incorporated by reference herein. [0170]
Additional methods of analyzing nucleic acids include amplification-based methods including polymerase chain reaction (PCR), ligase chain reaction (LCR), mini-PCR, rolling circle amplification, autocatalytic methods, such as those using Qβ replicase, TAS, 3SR, and any other suitable method known to those of skill in the art. [0171]
Other methods for analysis and identification and detection of polymorphisms, include but are not limited to, allele specific probes, Southern analyses, and other such analyses. [0172]
The methods described below provide ways to fragment given amplified or non-amplified nucleotide sequences thereby producing a set of mass signals when mass spectrometry is used to analyze the fragment mixtures. [0173]
Amplified fragments are yielded by standard polymerase chain methods (U.S. Pat. Nos. 4,683,195 and 4,683,202). The fragmentation method involves the use of enzymes that cleave single or double strands of DNA and enzymes that ligate DNA. The cleavage enzymes can be glycosylases, nickases, and site-specific and non site-specific nucleases, such as, but are not limited to, glycosylases, nickases and site-specific nucleases. [0174]
Glycosylase Fragmentation Method [0175]
DNA glycosylases specifically remove a certain type of nucleobase from a given DNA fragment. These enzymes can thereby produce abasic sites, which can be recognized either by another cleavage enzyme, cleaving the exposed phosphate backbone specifically at the abasic site and producing a set of nucleobase specific fragments indicative of the sequence, or by chemical means, such as alkaline solutions and or heat. The use of one combination of a DNA glycosylase and its targeted nucleotide would be sufficient to generate a base specific signature pattern of any given target region. [0176]
Numerous DNA gicosylases are known, For example, a DNA glycosylase can be uracil-DNA glycolsylase (UDG) , 3-methyladenine DNA glycosylase, 3-methyladenine DNA glycosylase II, pyrimidine hydrate-DNA glycosylase, FaPy-DNA glycosylase, thymine mismatch-DNA glycosylase, hypoxanthine-DNA glycosylase, 5-Hydroxymethyluracil DNA glycosylase (HmUDG), 5-Hydroxymethylcytosine DNA glycosylase, or 1,N6-etheno-adenine DNA glycosylase (see, e.g.,, U.S. Pat. Nos. 5,536,649, 5,888, 795, 5,952,176 and 6,099,553, International PCT application Nos. WO 97/03210, WO 99/54501; see, also, Eftedal et al. (1993) Nucleic Acids Res 21:2095-2101, Bjelland and Seeberg (1987) Nucleic Acids Res. 15:2787-2801, Saparbaev et al. (1995) Nucleic Acids Res. 23:3750-3755, Bessho (1999) Nucleic Acids Res. 27:979-983) corresponding to the enzyme's modified nucleotide or nucleotide analog target. uracil-DNA glycolsylase (UDG) is an exemplary glycosylase. [0177]
Uracil, for example, can be incorporated into an amplified DNA molecule by amplifying the DNA in the presence of normal DNA precursor nucleotides (e.g. dCTP, dATP, and dGTP) and dUTP. When the amplified product is treated with UDG, uracil residues are cleaved. Subsequent chemical treatment of the products from the UDG reaction results in the cleavage of the phosphate backbone and the generation of nucleobase specific fragments. Moreover, the separation of the complementary strands of the amplified product prior to glycosylase treatment allows complementary patterns of fragmentation to be generated. Thus, the use of dUTP and Uracil DNA glycosylase allows the generation of T specific fragments for the complementary strands, thus providing information on the T as well as the A positions within a given sequence. Similar to this, a C-specific reaction on both (complementary) strands (i.e. with a C-specific glycosylase) yields information on C as well as G positions within a given sequence if the fragmentation patterns of both amplification strands are analyzed separately. Thus, with the glycosylase method and mass spectrometry, a full series of A, C, G and T specific fragmentation patterns can be analyzed. [0178]
Nickase Fragmentation Method [0179]
A DNA nickase, or DNase, can be used to recognize and cleave one strand of a DNA duplex. Numerous nickases are known. Among these, for example, are nickase NY2A nickase and NYS1 nickase (Megabase) with the following cleavage sites: [0180]
NY2A: 5′ . . . R AG . . . 3′[0181]
3′ . . . Y TC . . . 5′ where R=A or G and Y=C or T [0182]
NYS1: 5′ . . . CC[A/G/T] . . . 3′[0183]
3′ . . . GG[T/C/A] . . . 5′. [0184]
Fen-Ligase Fragmentation Method [0185]
The Fen-ligase method involves two enzymes: Fen-1 enzyme and a ligase. The Fen-1 enzyme is a site-specific nuclease known as a “flap” endonuclease (U.S. Pat. Nos. 5,843,669, 5,874,283, and 6,090,606). This enzyme recognizes and cleaves DNA “flaps” created by the overlap of two oligonucleotides hybridized to a target DNA strand. This cleavage is highly specific and can recognize single base pair mutations, permitting detection of a single homologue from an individual heterozygous at one SNP of interest and then genotyping that homologue at other SNPs occurring within the fragment. Fen-1 enzymes can be Fen-1 like nucleases e.g. human, murine, and Xenopus XPG enzymes and yeast RAD2 nucleases or Fen-1 endonucleases from, for example, [0186] M. jannaschii, P. furiosus, and P. woesei. Among such enzymes are the Fen-1 enzymes.
The ligase enzyme forms a phosphodiester bond between two double stranded nucleic acid fragments. The ligase can be DNA Ligase I or DNA Ligase IlIl (see, e.g., U.S. Pat. Nos. 5,506,137, 5,700,672, 5,858,705 and 5,976,806; see, also, Waga, et al. (1994) J. Biol. Chem. 269:10923-10934, Li et al. (1994) Nucleic Acids Res. 22:632-638, Arrand et al. (1986) J. Biol. Chem. 261:9079-9082, Lehman (1974) Science 186:790-797, Higgins and Cozzarelli (1979) Methods Enzymol. 68:50-71, Lasko et al. (1990) Mutation Res. 236:277-287, and Lindahl and Barnes (1992) Ann. Rev. Biochem. 61:251-281 ). Thermostable ligase (Epicenter Technologies), where “thermostable” denotes that the ligase retains activity even after exposure to temperatures necessary to separate two strands of DNA, are among the ligases for use herein. [0187]
Type IIS Enzyme Fragmentation Method [0188]
Restriction enzymes bind specifically to and cleave double-stranded DNA at specific sites within or adjacent to a particular recognition sequence. These enzymes have been classified into three groups (e.g. Types I, II, and III) as known to those of skill in the art. Because of the properties of type I and type III enzymes, they have not been widely used in molecular biological applications. Thus, for purposes herein type II enzymes are among those contemplated. Of the thousands of restriction enzymes known in the art, there are 179 different type II specificities. Of the 179 unique type II restriction endonucleases, 31 have a 4-base recognition sequence, 11 have a 5-base recognition sequence, 127 have a 6-base recognition sequence, and 10 have recognition sequences of greater than six bases (U.S. Pat. No. 5,604,098). Of category type II enzymes, type IIS is exemplified herein. [0189]
Type IIS enzymes can be Alw XI, Bbv I, [0190] Bce 83, Bpm I, Bsg I, Bsm AI, Bsm FI, Bsa I, Bcc I, Bcg I, Ear I, Eco 57I, Esp 3I, Fau I, Fok I, Gsu I, Hga I, Mme I, Mbo II, Sap I, and the otheres.
The Fok I enzyme endonuclease is an exemplary well characterized member of the Type IIS class (see, e.g., U.S. Pat. Nos. 5,714,330, 5,604,098, 5,436,150, 6,054,276 and 5,871,911; see, also, Szybalski et al. (1991 ) Gene 100:13-26, Wilson and Murray (1991) Ann. Rev. Genet. 25:585-627, Sugisaki et al. (1981) Gene 16:73-78, Podhajska and Szalski (1985) Gene 40:175-182. Fok I recognizes the [0191] sequence 5′GGATG-3′ and cleaves DNA accordingly. Type IIS restriction sites can be introduced into DNA targets by incorporating the sites into primers used to amplify such targets. Fragments produced by digestion with Fok I are site specific and can be analyzed by mass spectrometry methods such as MALDI-TOF mass spectrometry, ESI-TOF mass spectrometry, and any other type of mass spectrometry well known to those of skill in the art.
Once a polymorphism has been found to correlate with a parameter such as age, age groups can be screened for polymorphisms. The possibility of false results due to allelic dropout is examined by doing comparative PCR in an adjacent region of the genome. [0192]
Analyses [0193]
In using the database, allelic frequencies can be determined across the population by analyzing each sample in the population individually, determining the presence or absence of allele or marker of interest in each individual sample, and then determining the frequency of the marker in the population. The database can then be sorted (stratified) to identify any correlations between the allele and a selected parameter using standard statistical analysis. If a correlation is observed, such as a decrease in a particular marker with age or correlation with sex or other parameter, then the marker is a candidate for further study, such as genetic mapping to identify a gene or pathway in which it is involved. The marker can then be correlated, for example, with a disease. Haplotying also can be carried out. Genetic mapping can be effected using standard methods and can also require use of databases of others, such as databases previously determined to be associated with a disorder. [0194]
Exemplary analyses have been performed and these are shown in the figures, and discussed herein. [0195]
Sample Pooling [0196]
It has been found that using the databases provided herein, or any other database of such information, substantially the same frequencies that were obtained by examining each sample separately can be obtained by pooling samples, such as in batches of 10, 20, 50, 100, 200, 500, 1000 or any other number. A precise number can be determined empirically if necessary, and can be as low as 3. [0197]
In one embodiment, the frequency of genotypic and other markers can be obtained by pooling samples. To do this a target population and a genetic variation to be assessed is selected, a plurality of samples of biopolymers are obtained from members of the population, and the biopolymer from which the marker or genotype can be inferred is determined or detected. A comparison of samples tested in pools and individually and the sorted results therefrom are shown in FIG. 9, which shows frequency of the [0198] factor VII Allele 353Q. FIG. 10 depicts the frequency of the CETP Allele in pooled versus individual samples. FIG. 15 shows ethnic diversity among various ethnic groups in the database using pooled DNA samples to obtain the data. FIGS. 12-14 show mass spectra for these samples.
Pooling of test samples has application not only to the healthy databases provided herein, but also to use in gathering data for entry into any database of subjects and genotypic information, including typical databases derived from diseased populations. What is demonstrated herein, is the finding that the results achieved are statistically the same as the results that would be achieved if each sample is analyzed separately. Analysis of pooled samples by a method, such as the mass spectrometric methods provided herein, permits resolution of such data and quantitation of the results. [0199]
For factor VII the R53Q acid polymorphism was assessed. In FIG. 9, the “individual” data represent allelic frequency observed in 92 individuals reactions. The pooled data represent the allelic frequency of the same 92 individuals pooled into a single probe reaction. The concentration of DNA in the samples of individual donors is 250 nanograms. The total concentration of DNA in the pooled samples is also 250 nanograms, where the concentration of any individual DNA is 2.7 nanograms. [0200]
It also was shown that it is possible to reduce the DNA concentration of individuals in a pooled samples from 2.7 nanograms to 0.27 nanograms without any change in the quality of the spectrum or the ability to quantitate the amount of sample detected. Hence low concentrations of sample can be used in the pooling methods. [0201]
Use of the Databases and Markers Identified Thereby [0202]
The successful use of genomics requires a scientific hypothesis (i.e., common genetic variation, such as a SNP), a study design (i.e., complex disorders), samples and technology, such as the chip-based mass spectrometric analyses (see, e.g., U.S. Pat. No. 5,605,798, U.S. Pat. No. 5,777,324, U.S. Pat. No. 6,043,031, allowed copending U.S. application Ser. No. 08/744,481, U.S. application Ser. No. 08/990,851, International PCT application No. WO 98/20019, copending U.S. application Ser. No. 09/285,481, which describes an automated process line for analyses; see, also, U.S. application Ser. Nos. 08/617,256, 09/287,681, 09/287,682, 09/287,141 and 09/287,679, allowed copending U.S. application Ser. No. 08/744,481, International PCT application No. PCT/US97/20444, published as International PCT application No. WO 98/20019, and based upon U.S. application Ser. Nos. 08/744,481, 08/744,590, 08/746,036, 08/746,055, 08/786,988, 08/787,639, 08/933,792, 08/746,055, 09/266,409, 08/786,988 and 08/787,639; see, also U.S. application Ser. No. 09/074,936). All of these aspects can be used in conjunction with the databases provided herein and samples in the collection. [0203]
The databases and markers identified thereby can be used, for example, for identification of previously unidentified or unknown genetic markers and to identify new uses for known markers. As markers are identified, these can be entered into the database to use as sorting parameters from which additional correlations can be determined. [0204]
Previously Unidentified or Unknown Genetic Markers [0205]
The samples in the healthy databases can be used to identify new polymorphisms and genetic markers, using any mapping, sequencing, amplification and other methodologies, and in looking for polymorphisms among the population in the database. The thus-identified polymorphism can then be entered into the database for each sample, and the database sorted (stratified) using that polymorphism as a sorting parameter to identify any patterns and correlations that emerge, such as age correlated changes in the frequency of the identified marker. If a correlation is identified, the locus of the marker can be mapped and its function or effect assessed or deduced. [0206]
Thus, the databases here provide means for: [0207]
identification of significantly different allelic frequencies of genetic factors by comparing the occurrence or disappearance of the markers with increasing age in population and then associating the markers with a disease or a biochemical pathway; [0208]
identification of significantly different allelic frequencies of disease causing genetic factors by comparing the male with the female population or comparing other selected stratified populations and associating the markers with a disease or a biochemical pathway; [0209]
identification of significantly different allelic frequencies of disease causing genetic factors by comparing different ethnic groups and associating the markers with a disease or a biochemical pathway that is known to occur in high frequency in the ethnic group; [0210]
profiling potentially functional variants of genes through the general panmixed population stratified according to age, sex, and ethnic origin and thereby demonstrating the contribution of the variant genes to the physical condition of the investigated population; [0211]
identification of functionally relevant gene variants by gene disequilibrium analysis performed within the general panmixed population stratified according to age, sex, and ethnic origin and thereby demonstrating their contribution to the physical condition of investigated population; [0212]
identification of potentially functional variants of chromosomes or parts of chromosomes by linkage disequilibrium analysis performed within the general panmixed population stratified according to age, sex, and ethnic origin and thereby demonstrating their contribution to the physical condition of investigated population. [0213]
Uses of the Identified Markers and Known Markers [0214]
The databases can also be used in conjunction with known markers and sorted to identify any correlations. For example, the databases can be used for: [0215]
determination and evaluation of the penetrance of medically relevant polymorphic markers; [0216]
determination and evaluation of the diagnostic specificity of medically relevant genetic factors; [0217]
determination and evaluation of the positive predictive value of medically relevant genetic factors; [0218]
determination and evaluation of the onset of complex diseases, such as, but are not limited to, diabetes, hypertension, autoimmune diseases, arteriosclerosis, cancer and other diseases within the general population with respect to their causative genetic factors; [0219]
delineation of the appropriate strategies for preventive disease treatment; [0220]
delineation of appropriate timelines for primary disease intervention; [0221]
validation of medically relevant genetic factors identified in isolated populations regarding their general applicability; [0222]
validation of disease pathways including all potential target structures identified in isolated populations regarding their general applicability; and [0223]
validation of appropriate drug targets identified in isolated populations regarding their general applicability. [0224]
Among the diseases and disorders for which polymorphisms can be linked include, those linked to inborn errors of metabolism, acquired metabolic disorders, intermediary metabolism, oncogenesis pathways, blood clotting pathways, and DNA synthetic and repair pathways, DNA repair/replication/transcription factors and activities, e.g., such as genes related to oncogenesis, aging and genes involved in blood clotting and the related biochemical pathways that are related to thrombosis, embolism, stroke, myocardial infarction, angiogenesis and oncogenesis. [0225]
For example, a number of diseases are caused by or involve deficient or defective enzymes in intermediary metabolism (see, e.q., Tables 1 and 2, below) that result, upon ingestion of the enzyme substrates, in accumulation of harmful metabolites that damage organs and tissues, particularly an infant's developing brain and other organs, resulting in mental retardation and other developmental disorders. [0226]
Identification of Markers and Genes for Such Disorders is of Great Interest. [0227]
Model Systems [0228]
Several gene systems, p21, p53 and Lipoprotein Lipase polymorphism (N291S), were selected. The p53 gene is a tumor suppressor gene that is mutated in diverse tumor types. One common allelic variant occurs at [0229] codon 72. A polymorphism that has been identified in the p53 gene, i.e., the R72P allele, results in an amino acid exchange, arginine to proline, at codon 72 of the gene.
Using diseased populations, it has been shown that there are ethnic differences in the allelic distribution of these alleles among African-Americans and Caucasians in the U.S. The results here support this finding and also demonstrate that the results obtained with a healthy database are meaningful (see, FIG. 7B). [0230]
The 291S allele leads to reduced levels of high density lipoprotein cholesterol (HDL-C) that is associated with an increased risk of males for arteriosclerosis and in particular myocardial infarction (see, Reymer et al. (1995) [0231] Nature Genetics 10:28-34).
Both genetic polymorphisms were profiled within a part of the Caucasian population-based sample bank. For the polymorphism located in the lipoprotein lipase gene a total of 1025 unselected individuals (436 males and 589 females) were tested. Genomic DNA was isolated from blood samples obtained from the individuals. [0232]
As shown in the Examples and figures, an exemplary database containing about 5000 subjects, answers to the questionnaire (see FIG. 3), and genotypic information has been stratified. A particular known allele has been selected, and the samples tested for the marker using mass spectrometric analyses, particularly PROBE (see the EXAMPLES) to identify polymorphisms in each sample. The population in the database has been sorted according to various parameters and correlations have been observed. For example, FIGS. [0233] 2A-C, show sorting of the data by age and sex for the Lipoprotein Lipase gene in the Caucasian population in the database. The results show a decrease in the frequency of the allele with age in males but no such decrease in females. Other alleles that have been tested against the database, include, alleles of p53, p21 and factor VII. Results when sorted by age are shown in the figures.
These examples demonstrate an effect of altered frequency of disease causing genetic factors within the general population. The scientific interpretation of those results allows prediction of medical relevance of polymorphic genetic alterations. In addition, conclusions can be drawn with regard to their penetrance, diagnostic specificity, positive predictive value, onset of disease, most appropriate onset of preventive strategies, and the general applicability of genetic alterations identified in isolated populations to panmixed populations. [0234]
Therefore, an age- and sex-stratified population-based sample bank that is ethnically homogenous is a suitable tool for rapid identification and validation of genetic factors regarding their potential medical utility. [0235]
Exemplary Computer System for Creating, Storing and Processing the Databases [0236]
Systems [0237]
Systems, including computers, containing the databases are provided herein. The computers and databases can be used in conjunction, for example, with the APL system (see, copending U.S. application Ser. No. 09/285,481), which is an automated system for analyzing biopolymers, particularly nucleic acids. Results from the APL system can be entered into the database. [0238]
Any suitable computer system can be used. The computer system can be integrated into systems for sample analysis, such as the automated process line described herein (see, e.g., copending U.S. application Ser. No. 09/285,481). [0239]
FIG. 17 is a block diagram of a computer constructed to provide and process the databases described herein. The processing that maintains the database and performs the methods and procedures can be performed on multiple computers all having a similar construction, or can be performed by a single, integrated computer. For example, the computer through which data are added to the database can be separate from the computer through which the database is sorted, or can be integrated with it. In either arrangement, the computers performing the processing can have a construction as illustrated in FIG. 17. [0240]
FIG. 17 is a block diagram of an [0241] exemplary computer 1700 that maintains the database described above and performs the methods and procedures. Each computer 1700 operates under control of a central processor unit (CPU) 1702, such as a “Pentium” microprocessor and associated integrated circuit chips, available from Intel Corporation of Santa Clara, Calif., USA. A computer user can input commands and data from a keyboard and display mouse 1704 and can view inputs and computer output at a display 1706. The display is typically a video monitor or flat panel display device. The computer 1700 also includes a direct access storage device (DASD) 1707, such as a fixed hard disk drive. The memory 1708 typically comprises volatile semiconductor random access memory (RAM). Each computer can include a program product reader 1710 that accepts a program product storage device 1712, from which the program product reader can read data (and to which it can optionally write data). The program product reader can comprise, for example, a disk drive, and the program product storage device can comprise removable storage media such as a magnetic floppy disk, an optical CD-ROM disc, a CD-R disc, a CD-RW disc, or a DVD data disc. If desired, the computers can be connected so they can communicate with each other, and with other connected computers, over a network 1713. Each computer 1700 can communicate with the other connected computers over the network 1713 through a network interface 1714 that enables communication over a connection 1716 between the network and the computer.
The [0242] computer 1700 operates under control of programming steps that are temporarily stored in the memory 1708 in accordance with conventional computer construction. When the programming steps are executed by the CPU 1702, the pertinent system components perform their respective functions. Thus, the programming steps implement the functionality of the system as described above. The programming steps can be received from the DASD 1707, through the program product reader 1712, or through the network connection 1716. The storage drive 1710 can receive a program product, read programming steps recorded thereon and transfer the programming steps into the memory 1708 for execution by the CPU 1702. As noted above, the program product storage device 1710 can comprise any one of multiple removable media having recorded computer-readable instructions, including magnetic floppy disks and CD-ROM storage discs. Other suitable program product storage devices can include magnetic tape and semiconductor memory chips. In this way, the processing steps necessary for operation can be embodied on a program product.
Alternatively, the program steps can be received into the [0243] operating memory 1708 over the network 1713. In the network method, the computer receives data including program steps into the memory 1708 through the network interface 1714 after network communication has been established over the network connection 1716 by well-known methods that will be understood by those skilled in the art without further explanation. The program steps are then executed by the CPU 1702 to implement the processing of the Garment Database system.
It should be understood that all of the computers of the system and can have a construction similar to that shown in FIG. 17. Details described with respect to the FIG. 17 [0244] computer 1700 will be understood to apply to all computers of the system 1700. This is indicated by multiple computers 1700 shown connected to the network 1713. Any one of the computers 1700 can have an alternative construction, so long as they can communicate with the other computers and support the functionality described herein.
FIG. 18 is a flow diagram that illustrates the processing steps performed using the computer illustrated in FIG. 17, to maintain and provide access to the databases, such as for identifying polymorphic genetic markers. In particular, the information contained in the database is stored in computers having a construction similar to that illustrated in FIG. 17. The first step for maintaining the database, as indicated in FIG. 18, is to identify healthy members of a population. As noted above, the population members are subjects that are selected only on the basis of being healthy, and where the subjects are mammals, such as humans, they can be selected based upon apparent health and the absence of detectable infections. The step of identifying is represented by the flow diagram box numbered 1802. [0245]
The next step, represented by the flow diagram box numbered 1804, is to obtain identifying and historical information and data relating to the identified members of the population. The information and data comprise parameters for each of the population members, such as member age, ethnicity, sex, medical history, and ultimately genotypic information. Initially, the parameter information is obtained from a questionnaire answered by each member, from whom a body tissue or body fluid sample also is obtained. The step of entering and storing these parameters into the database of the computer is represented by the flow diagram box numbered 1806. As additional information about each population member and corresponding sample is obtained, this information can be inputted into the database and can serve as a sorting parameter. [0246]
In the next step, represented by the flow diagram box numbered 1808, the parameters of the members are associated with an indexer. This step can be executed as part of the database storage operation, such as when a new data record is stored according to the relational database structure and is automatically linked with other records according to that structure. The [0247] step 1806 also can be executed as part of a conventional data sorting or retrieval process, in which the database entries are searched according to an input search or indexing key value to determine attributes of the data. For example, such search and sort techniques can be used to follow the occurrence of known genetic markers and then determine if there is a correlation with diseases for which they have been implicated. Examples of this use are for assessing the frequencies of the p53 and Lipoprotein Lipase polymorphisms.
Such searching of the database also can be valuable for identifying one or more genetic markers whose frequency changes within the population as a function of age, ethnic group, sex, or some other criteria. This can allow the identification of previously unknown polymorphisms and, ultimately, identification of a gene or pathway involved in the onset and progression of disease. [0248]
In addition, the database can be used for taking an identified polymorphism and ascertaining whether it changes in frequency when the data are sorted according to a selected parameter. [0249]
In this way, the databases and methods provided herein permit, among other things, identification of components, particularly key components, of a disease process by understanding its genetic underpinnings, and also an understanding of processes, such as individual drug responses. The databases and methods provided herein also can be used in methods involving elucidation of pathological pathways, in developing new diagnostic assays, identifying new potential drug targets, and in identifying new drug candidates. [0250]
Morbidity and/or Early Mortality Associated Polymorphisms [0251]
A database containing information provided by a population of healthy blood donors who were not selected for any particular disease to can be used to identify polymorphisms and the alleles in which they are present, whose frequency decreases with age. These can represent morbidity susceptibility markers and genes. [0252]
Polymorphisms of the genome can lead to altered gene function, protein function or genome instability. To identify those polymorphisms which have a clinical relevance/utility is the goal of a world-wide scientific effort. It can be expected that the discovery of such polymorphisms will have a fundamental impact on the identification and development of novel drug compounds to cure diseases. The strategy to identify valuable polymorphisms is cumbersome and dependent upon the availability of many large patient and control cohorts to show disease association. In particular, genes that cause a general risk of the population to suffer from any disease (morbidity susceptibility genes) will escape these case/control studies entirely. [0253]
Here described is a screening strategy to identify morbidity susceptibility genes underlying a variety of different diseases. The definition of a morbidity susceptibility gene is a gene that is expressed in many different cell types or tissues (housekeeping gene) and its altered function can facilitate the expression of a clinical phenotype caused by disease-specific susceptibility genes that are involved in a pathway specific for this disorder. In other words, these morbidity susceptibility genes predispose people to develop a distinct disease according to their genetic make-up for this disease. [0254]
Candidates for morbidity susceptibility genes can be found at the bottom level of pathways involving transcription, translation, heat-shock proteins, protein trafficking, DNA repair, assembly systems for subcellular structures (e.g. mitochondria, peroxysomes and other cellular microbodies), receptor signaling cascades, immunology, etc. Those pathways control the quality of life at the cellular level as well as for the entire organism. Mutations/polymorphisms located in genes encoding proteins for those pathways can reduce the fitness of cells and make the organism more susceptible to express the clinical phenotype caused by the action of a disease-specific susceptibility gene. Therefore, these morbidity susceptibility genes can be potentially involved in a whole variety of different complex diseases if not in all. Disease-specific susceptibility genes are involved in pathways that can be considered as disease-specific pathways like glucose-, lipid, hormone metabolism, etc. [0255]
The exemplified method permit, among other things, identification of genes and/or gene products involved in a man's general susceptibility to morbidity and/or mortality; use of these genes and/or gene products in studies to elucidate the genetic underpinnings of human diseases; use of these genes and/or gene products in combinatorial statistical analyses without or together with disease-specific susceptibility genes; use of these genes and/or gene products to predict penetrance of disease susceptibility genes; use of these genes and/or gene products in predisposition and/or acute medical diagnostics and use of these genes and/or gene products to develop drugs to cure diseases and/or to extend the life span of humans. [0256]
Screening Process [0257]
The healthy population stratified by age, gender and ethnicity, etc. is a very efficient and a universal screening tool for morbidity associated genes. Changes of allelic frequencies in the young compared to the old population are expected to indicate putative morbidity susceptibility genes. Individual samples of this healthy population base can be pooled to further increase the throughput. In an experiment, pools of young and old Caucasian females and males were applied to screen more than 400 randomly chosen single nucleotide polymorphisms located in many different genes. Candidate polymorphisms were identified if the allelic difference was greater than 8% between young and old for both or only one of the genders. The initial results were assayed again in at least one independent subsequent experiments. Repeated experiments are necessary to recognize unstable biochemical reactions, which occur with a frequency of about 2-3% and can mimic age-related allelic frequency differences. Average frequency differences and standard deviations are calculated after successful reproducibility of initial results. The final allelic frequency is then compared to a reference population of Caucasian CEPH sample pool. The result should show similar allelic frequencies in the young Caucasian population. Subsequently, the exact allele frequencies of candidates including genotype information were obtained by analyzing all individual samples. This procedure is straight forward with regard to time and cost. It enables the screening of an enormous number of SNPs. So far, several markers with a highly significant association to age were identified and described below. [0258]
In general at least 5 individuals in a stratified population should to be screened to produce statistically significant results. The frequency of the allele is determined for an age stratified population. Chi square analysis is then performed on the allelic frequencies to determine if the difference between age groups is statistically significant. A p value less than of 0.1 is considered to represent a statistically significant difference. Typically the p value should be less than 0.05. [0259]
Clinical Trials [0260]
The identification of markers whose frequency in a population decreases with age also allows for better designed and balanced clinical trials. Currently, if a clinical trial utilizes a marker as a significant endpoint in a study and the marker disappears with age, then the results of the study can be inaccurate. By using methods provided herein, it can be ascertained that if a marker decreases in frequency with age. This information can be considered and controlled when designing the study. For, example, an age independent marker could be substituted in its place. [0261]
The following examples are included for illustrative purposes only and are not intended to limit the scope of the invention. [0262]

EXAMPLE 1

This example describes the use of a database containing information provided by a population of healthy blood donors who were not selected for any particular disease to determine the distribution of allelic frequencies of known genetic markers with age and by sex in a Caucasian subpopulation of the database. The results described in this example demonstrate that a disease-related genetic marker or polymorphism can be identified by sorting a healthy database by a parameter or parameters, such as age, sex and ethnicity. [0263]
Generating a Database [0264]
Blood was obtained by venous puncture from human subjects who met blood bank criteria for donating blood. The blood samples were preserved with EDTA at pH 8.0 and labeled. Each donor provided information such as age, sex, ethnicity, medical history and family medical history. Each sample was labeled with a barcode representing identifying information. A database was generated by entering, for each donor, the subject identifier and information corresponding to that subject into the memory of a computer storage medium using commercially available software, e.g., Microsoft Access. [0265]
Model Genetic Markers [0266]
The frequencies of polymorphisms known to be associated at some level with disease were determined in a subpopulation of the subjects represented in the database. These known polymorphisms occur in the p21, p53 and Lipoprotein Lipase genes. Specifically, the N291S polymorphism (N291S) of the Lipoprotein Lipase gene, which results in a substitution of a serine for an asparagine at amino acid codon 291, leads to reduced levels of high density lipoprotein cholesterol (HDL-C) that is associated with an increased risk of males for arteriosclerosis and in particular myocardial infarction (see, Reymer et al. (1995) [0267] Nature Genetics 10:28-34).
The p53 gene encodes a cell cycle control protein that assesses DNA damage and acts as a transcription factor regulating genes that control cell growth, DNA repair and apoptosis (programmed cell death). Mutations in the p53 gene have been found in a wide variety of different cancers, including different types of leukemia, with varying frequency. The loss of normal p53 function results in genomic instability an uncontrolled cell growth. A polymorphism that has been identified in the p53 gene, i.e., the R72P allele, results in the substitution of a proline for an arginine at [0268] amino acid codon 72 of the gene.
The p21 gene encodes a cyclin-dependent kinase inhibitor associated with G1phase arrest of normal cells. Expression of the p21 gene triggers apoptosis. Polymorphisms of the p21 gene have been associated with Wilms' tumor, a pediatric kidney cancer. One polymorphism of the p21 gene, the S31R polymorphism, results in a substitution of an arginine for a serine at [0269] amino acid codon 31.
Database Analysis [0270]
Sorting of Subjects According to Specific Parameters [0271]
The genetic polymorphisms were profiled within segments of the Caucasian subpopulation of the sample bank. For p53 profiling, the genomic DNA isolated from blood from a total of 1277 Caucasian subjects age 18-59 years and 457 Caucasian subjects age 60-79 years was analyzed. For p21 profiling, the genomic DNA isolated from blood from a total of 910 Caucasian subjects age 18-49 years and 824 Caucasian subjects age 50-79 years was analyzed. For lipoprotein lipase gene profiling, the genomic DNA from a total of 1464 Caucasian females and 1470 Caucasian males under 60 years of age and a total of 478 Caucasian females and 560 Caucasian males over 60 years of age was analyzed. [0272]
Isolation and Analysis of Genomic DNA [0273]
Genomic DNA was isolated from blood samples obtained from the individuals. Ten milliliters of whole blood from each individual was centrifuged at 2000×g. One milliliter of the buffy coat was added to 9 ml of 155 mM NH[0274] ₄Cl, 10 mM KHCO₃, and 0.1 mM Na₂EDTA, incubated 10 min at room temperature and centrifuged for 10 min at 2000×g. The supernatant was removed, and the white cell pellet was washed in 155 mM NH₄Cl, 10 mM KHCO₃and 0.1 mM Na₂EDTA and resuspended in 4.5 ml of 50 mM Tris, 5 mM EDTA and 1% SDS. Proteins were precipitated from the cell lysate by 6 mM ammonium acetate, pH 7.3, and then separated from the nucleic acids by centrifugation at 3000×g. The nucleic acid was recovered from the supernatant by the addition of an equal volume of 100% isopropanol and centrifugation at 2000×g. The dried nucleic acid pellet was hydrated in 10 mM Tris, pH 7.6, and 1 mM Na₂EDTA and stored at 4° C.
Assays of the genomic DNA to determine the presence or absence of the known genetic markers were developed using the BiomassPROBE™ detection method (primer oligo base extension) reaction. This method uses a single detection primer followed by an oligonucleotide extension step to give products, which can be readily resolved by mass spectrometry, and, in particular, MALDI-TOF mass spectrometry. The products differ in length depending on the presence or absence of a polymorphism. In this method, a detection primer anneals adjacent to the site of a variable nucleotide or sequence of nucleotides, and the primer is extended using a DNA polymerase in the presence of one or more dideoxyNTPs and, optionally, one or more deoxyNTPs. The resulting products are resolved by MALDI-TOF mass spectrometry. The mass of the products as measured by MALDI-TOF mass spectrometry makes possible the determination of the nucleotide(s) present at the variable site. [0275]
First, each of the Caucasian genomic DNA samples was subjected to nucleic acid amplification using primers corresponding to [0276] sites 5′ and 3′ of the polymorphic sites of the p21 (S31R allele), p53 (R72P allele) and Lipoprotein Lipase (N291S allele) genes. One primer in each primer pair was biotinylated to permit immobilization of the amplification product to a solid support. Specifically, the polymerase chain reaction primers used for amplification of the relevant segments of the p21, p53 and lipoprotein lipase genes are shown below: US4p21c31-2F (SEQ ID NO: 9) and US5p21-2R (SEQ ID NO: 10) for p21 gene amplification; US4-p53-ex4-F (also shown as p53-ex4US4 (SEQ ID NO: 2)) and US5-p53/2-4R (also shown as US5P53/4R (SEQ ID NO: 3)) for p53 gene amplification; and US4-LPL-F2 (SEQ ID NO: 16) and US5-LPL-R2 (SEQ ID NO: 17) for lipoprotein lipase gene amplification.
Amplification of the respective DNA sequences was conducted according to standard protocols. For example, primers can be used in a concentration of 8 pmol. The reaction mixture (e.g., [0277] total volume 50 μl) can contain Taq-polymerase including 10×buffer and dTNPs. Cycling conditions for polymerase chain reaction amplification can typically be initially 5 min. at 95° C., followed by 1 min. at 94° C., 45 sec at 53° C., and 30 sec at 72° C. for 40 cycles with a final extension time of 5 min at 72° C. Amplification products can be purified by using Qiagen's PCR purification kit (No. 28106) according to manufacturer's instructions. The elution of the purified products from the column can be done in 50 μl TE-buffer (10 mM Tris, 1 mM EDTA, pH 7.5).
The purified amplification products were immobilized via a biotin-avidin linkage to streptavidin-coated beads and the double-stranded DNA was denatured. A detection primer was then annealed to the immobilized DNA using conditions such as, for example, the following: 50 μl annealing buffer (20 mM Tris, 10 mM KCl, 10 mM (NH[0278] ₄)₂SO₄, 2 mM MgSO₂, 1% Triton X-100, pH 8) at 50° C. for 10 min, followed by washing of the beads three times with 200 μl washing buffer (40 mM Tris, 1 mM EDTA, 50 mM NaCl, 0.1% Tween 20, pH 8.8) and once in 200 μl TE buffer.
The PROBE extension reaction was performed, for example, by using some components of the DNA sequencing kit from USB (No. 70770) and dNTPs or ddNTPs from Pharmacia. An exemplary protocol could include a total reaction volume of 45 μl, containing of 21 μl water, 6 μl Sequenase-buffer, 3 [0279] μl 10 mM DTT solution, 4.5 μp, 0.5 mM of three dNTPs, 4.5 μl, 2 mM the missing one ddNTP, 5.5 μl glycerol enzyme dilution buffer, 0.25 μl Sequenase 2.0, and 0.25 pyrophosphatase. The reaction can then by pipetted on ice and incubated for 15 min at room temperature and for 5 min at 37° C. The beads can be washed three times with 200 μl washing buffer and once with 60 μl of a 70 mM NH₄-Citrate solution.
The DNA was denatured to release the extended primers from the immobilized template. Each of the resulting extension products was separately analyzed by MALDI-TOF mass spectrometry using 3-hydroxypicolinic acid (3-HPA) as matrix and a UV laser. [0280]
Specifically, the primers used in the PROBE reactions are as shown below: P21/31-3 (SEQ ID NO: 12) for PROBE analysis of the p21 polymorphic site; P53/72 (SEQ ID NO: 4) for PROBE analysis of the p53 polymorphic site; and LPL-2 for PROBE analysis of the lipoprotein lipase gene polymorphic site. In the PROBE analysis of the p21 polymorphic site, the extension reaction was performed using dideoxy-C. The products resulting from the reaction conducted on a “wild-type” allele template (wherein [0281] codon 31 encodes a serine) and from the reaction conducted on a polymorphic S31R allele template (wherein codon 31 encodes an arginine) are shown below and designated as P21/31-3 Ser (wt) (SEQ ID NO: 13) and P21/31-3 Arg (SEQ ID NO: 14), respectively. The masses for each product as can be measured by MALDI-TOF mass spectrometry are also provided (i.e., 4900.2 Da for the wild-type product and 5213.4 Da for the polymorphic product).
In the PROBE analysis of the p53 polymorphic site, the extension reaction was performed using dideoxy-C. The products resulting from the reaction conducted on a “wild-type” allele template (wherein [0282] codon 72 encodes an arginine) and from the reaction conducted on a polymorphic R72P allele template (wherein codon 72 encodes a proline) are shown below and designated as Cod72 G Arg (wt) and Cod72 C Pro, respectively. The masses for each product as can be measured by MALDI-TOF mass spectrometry are also provided (i.e., 5734.8 Da for the wild-type product and 5405.6 Da for the polymorphic product).
In the PROBE analysis of the lipoprotein lipase gene polymorphic site, the extension reaction was performed using a mixture of ddA and ddT. The products resulting from the reaction conducted on a “wild-type” allele template (wherein codon 291 encodes an asparagine) and from the reaction conducted on a polymorphic N291S allele template (wherein codon 291 encodes a serine) are shown below and designated as 291Asn and 291Ser, respectively. The masses for each product as can be measured by MALDI-TOF mass spectrometry are also provided (i.e., 6438.2 Da for the wild-type product and 6758.4 Da for the polymorphic product). [0283]

P53-1 (R72P)


PCR Product length: 407 bp
US4-p53-ex4-F
ctg aggacctggt cctctgactg	(SEQ ID NO: 1)

ctcttttcac ccatctacag tcccccttgc cgtcccaagc aatggatgat ttgatgctgt

ccccggacga tattgaacaa tggttcactg aagacccagg tccagatgaa gctcccagaa
P53/72 72R
tgccagaggc tgctccccgc gtggcccctg caccagcagc tcctacaccg gcggcccctg

c 72P
caccagcccc ctcctggccc ctgtcatctt ctgtcccttc ccagaaaacc taccagggca

gctacggttt ccgtctgggc ttcttgcatt ctgggacagc caagtctgtg acttgcacgg

tcagttgccc tgaggggctg gcttccatga gacttcaa
US5-p53/2-4R

Primers (SEQ ID NOs: 2-4)

p53-ex4FUS4	ccc agt cac gac gtt gta aaa cgc tga gga cct ggt cct ctg ac

US5P53/4R	agc gga taa caa ttt cac aca ggt tga agt ctc atg gaa gcc

P53/72	gcc aga ggc tgc tcc cc

Masses

	Product Termination:
Allele	ddC	SEQ #	Length	Mass

P53/72	gccagaggctgctcccc	5	17	5132.4
Cod72 G Arg	gccagaggctgctccccgc	6	19	5734.8
(wt)
Cod72 C Pro	gccagaggctgctccccc	7	18	5405.6

Biotinylated US5 primer is used in the PCR amplification. [0286]
LPL-1 (N291S) [0287]

Amino acid exchange asparagine to serine at codon 291 of the lipoprotein lipase gene.


PCR Product length: 251 bp
US4-LPL-F2	(SEQ ID NO: 16)
gcgctccatt catctcttca tcgactctct gttgaatgaa gaaaatccaa gtaaggccta	(SEQ ID NO: 15)

caggtgcagt tccaaggaag cctttgagaa agggctctgc ttgagttgta gaaagaaccg
LPL-2 291N

ctgcaacaat ctgggctatg agatcaataa agtcagagcc aaaagaagca gcaaaatgta
g 291S

cctgaagact cgttctcaga tgccc
US4-LPL-R2

Primers (SEQ ID NOs: 16-18):

US4-LPL-F2	ccc agt cac gac gtt gta aaa cgg cgc tcc att cat ctc ttc

US5-LPL-R2	agc gga taa caa ttt cac aca ggg ggc atc tga gaa cga gtc

LPL-2	caa tct ggg cta tga gat ca

[0289]

Masses

Allele Product Termination: ddA, ddT SEQ # Length Mass

LPL-2 caatctgggctatgagatca 19 20 6141

291 Asn caatctgggctatgagatcaa 20 21 6438.2

291 Ser caatctgggctatgagatcagt 21 22 6758.4

Biotinylated US5 primer is used in the PCR amplification.

P21-1 (S31R)

Amino acid exchange serine to arginine at codon 31 of the tumor
suppressor gene p21. Product length: 207 bp
US4p21c3l-2F

gtcc gtcagaaccc atgcggcagc	(SEQ ID NO: 8)
p21/31-3 31S

aaggcctgcc gccgcctctt cggcccagtg gacagcgagc agctgagccg cgactgtgat
a 31R

gcgctaatgg cgggctgcat ccaggaggcc cgtgagcgat ggaacttcga ctttgtcacc

gagacaccac tggaggg
US5p21-2R

Primers (SEQ ID NOs: 9-11)

US4p21c31-2F	ccc agt cac gac gtt gta aaa cgg tcc gtc aga acc cat gcg g

US5p21-2R	agc gga taa caa ttt cac aca ggc tcc agt ggt gtc tcg gtg ac

P21/31-3	cag cga gca gct gag

[0291]

Masses

Allele Product Termination: ddC SEQ # Length Mass

P21/31-3 cagcgagcagctgag 12 15 4627

P21/31-3 Ser cagcgagcagctgagc 13 16 4900.2

(wt)

P21/31-3 Arg cagcgagcagctgagac 14 17 5213.4
Biotinylated US5 primer is used in the PCR amplification. [0292]
Each of the Caucasian subject DNA samples was individually analyzed by MALDI-TOF mass spectrometry to determine the identity of the nucleotide at the polymorphic sites. The genotypic results of each assay can be entered into the database. The results were then sorted according to age and/or sex to determine the distribution of allelic frequencies by age and/or sex. As depicted in the Figures showing histograms of the results, in each case, there was a differential distribution of the allelic frequencies of the genetic markers for the p21, p53 and lipoprotein lipase gene polymorphisms. [0293]
FIG. 8 shows the results of the p21 genetic marker assays and reveals a statistically significant decrease (from 13.3% to 9.2%) in the frequency of the heterozygous genotype (S31 R) in Caucasians with age (18-49 years of age compared to 50-79 years of age). The frequencies of the homozygous (S31 and R31) genotypes for the two age groups are also shown, as are the overall frequencies of the S31 and R31 alleles in the two age groups (designated as *S31 and *R31, respectively in the Figure). [0294]
FIGS. [0295] 7A-C show the results of the p53 genetic marker assays and reveals a statistically significant decrease (from 6.7% to 3.7%) in the frequency of the homozygous polymorphic genotype (P72) in Caucasians with age (18-59 years of age compared to 60-79 years of age). The frequencies of the homozygous “wild-type” genotype (R72) and the heterozygous genotype (R72P) for the two age groups are also shown, as are the overall frequencies of the R72 and P72 alleles in the two age groups (designated as *R72 and *P72, respectively in the Figure). These results are consistent with the observation that allele is not benign, as p53 regulates expression of a second protein, p21, which inhibits cyclin-dependent kinases (CDKs) needed to drive cells through the cell-cycle (a mutation in either gene can disrupt the cell cycle leading to increased cell division).
FIG. 2C shows the results of the lipoprotein lipase gene genetic marker assays and reveals a statistically significant decrease (from 1.97% to 0.54%) in the frequency of the polymorphic allele (S291) in Caucasian males with age (see also Reymer et al. (1995) [0296] Nature Genetics 10:28-34). The frequencies of this allele in Caucasian females of different age groups are also shown.

EXAMPLE 2

This example describes the use of MALDI-TOF mass spectrometry to analyze DNA samples of a number of subjects as individual samples and as pooled samples of multiple subjects to assess the presence or absence of a polymorphic allele (the 353Q allele) of the Factor VII gene and determine the frequency of the allele in the group of subjects. The results of this study show that essentially the same allelic frequency can be obtained by analyzing pooled DNA samples as by analyzing each sample separately and thereby demonstrate the quantitative nature of MALDI-TOF mass spectrometry in the analysis of nucleic acids. [0297]
Factor VII [0298]
Factor VII is a serine protease involved in the extrinsic blood coagulation cascade. This factor is activated by thrombin and works with tissue factor (Factor III) in the processing of Factor X to Factor Xa. There is evidence that supports an association between polymorphisms in the Factor VII gene and increased Factor VII activity which can result in an elevated risk of ischemic cardiovascular disease, including myocardial infarction. The polymorphism investigated in this study is R353Q (i.e., a substitution of a glutamic acid residue for an arginine residue at codon 353 of the Factor VII gene) (see Table 5). [0299]
Analysis of DNA Samples for the Presence or Absence of the 353Q Allele of the Factor VII Gene [0300]
Genomic DNA was isolated from separate blood samples obtained from a large number of subjects divided into multiple groups of 92 subjects per group. Each sample of genomic DNA was analyzed using the BiomassPROBE™ assay as described in Example 1 to determine the presence or absence of the 353Q polymorphism of the Factor VII gene. [0301]
First, DNA from each sample was amplified in a polymerase chain reaction using primers F7-353FUS4 (SEQ ID NO: 24) and F7-353RUS5 (SEQ ID NO: 26) as shown below and using standard conditions, for example, as described in Example 1. One of the primers was biotinylated to permit immobilization of the amplification product to a solid support. The purified amplification products were immobilized via a biotin-avidin linkage to streptavidin-coated beads and the double-stranded DNA was denatured. A detection primer was then annealed to the immobilized DNA using conditions such as, for example, described in Example 1. The detection primer is shown as F7-353-P (SEQ ID NO: 27) below. The PROBE extension reaction was carried out using conditions, for example, such as those described in Example 1. The reaction was performed using ddG. [0302]
The DNA was denatured to release the extended primers from the immobilized template. Each of the resulting extension products was separately analyzed by MALDI-TOF mass spectrometry. A matrix such as 3-hydroxypicolinic acid (3-HPA) and a UV laser could be used in the MALDI-TOF mass spectrometric analysis. The products resulting from the reaction conducted on a “wild-type” allele template (wherein codon 353 encodes an arginine) and from the reaction conducted on a polymorphic 353Q allele template (wherein codon 353 encodes a glutamic acid) are shown below and designated as 353 CGG and 353 CAG, respectively. The masses for each product as can be measured by MALDI-TOF mass spectrometry are also provided (i.e., 5646.8 Da for the wild-type product and 5960 Da for the polymorphic product). [0303]
The MALDI-TOF mass spectrometric analyses of the PROBE reactions of each DNA sample were first conducted separately on each sample (250 nanograms total concentration of DNA per analysis). The allelic frequency of the 353Q polymorphism in the group of 92 subjects was calculated based on the number of individual subjects in which it was detected. [0304]
Next, the samples from 92 subjects were pooled (250 nanograms total concentration of DNA in which the concentration of any individual DNA is 2.7 nanograms), and the pool of DNA was subjected to MALDI-TOF mass spectrometric analysis. The area under the signal corresponding to the mass of the 353Q polymorphism PROBE extension product in the resulting spectrum was integrated in order to quantitate the amount of DNA present. The ratio of this amount to total DNA was used to determine the allelic frequency of the 353Q polymorphism in the group of subjects. This type of individual sample vs. pooled sample analysis was repeated for numerous different groups of 92 different samples. [0305]
The frequencies calculated based on individual MALDI-TOF mass spectrometric analysis of the 92 separate samples of each group of 92 are compared to those calculated based on MALDI-TOF mass spectrometric analysis of pools of DNA from 92 samples in FIG. 9. These comparisons are shown as “pairs” of bar graphs in the Figure, each pair being labeled as a separate “pool” number, e.g., P1, P16, P2, etc. Thus, for example, for P1, the allelic frequency of the polymorphism calculated by separate analysis of each of the 92 samples was 11.41%, and the frequency calculated by analysis of a pool of all of the 92 DNA samples was 12.09%. [0306]
The similarity in frequencies calculated by analyzing separate DNA samples individually and by pooling the DNA samples demonstrates that it is possible, through the quantitative nature of MALDI-TOF mass spectrometry, to analyze pooled samples and obtain accurate frequency determinations. The ability to analyze pooled DNA samples significantly reduces the time and costs involved in the use of the non-selected, healthy databases as described herein. It has also been shown that it is possible to decrease the DNA concentration of the individual samples in a pooled mixture from 2.7 nanograms to 0.27 nanograms without any change in the quality of the spectrum or the ability to quantitate the amount of sample detected. [0307]
Factor VII R353Q PROBE Assay [0308]

PROBE Assay for cod353 CGG>CAG (Arg>Gln), Exon 9 G>A.


PCR fragment: 134 bp (incl. US tags; SEQ ID Nos. 22 and 23)
Frequency of A allele: Europeans about 0.1, Japanese/Chinese about
0.03-0.05 (Thromb. Haemost. 1995, 73:617-22; Diabetologia 1998,
41:760-6):

	F7-353FUS4>
1201	GTGCCGGCTA CTCGGATGGC AGCAAGGACT CCTGCAAGGG GGACAGTGGA GGCCCACATG

	F7-353-P> A <F7-353RUS5
1261	CCACCCACTA CCGGGGCACG TGGTACCTGA CGGGCATCGT CAGCTGGGGC CAGGGCTGCG

Primers	(SEQ ID NOs: 24-26)	Tm^gs
F7-353FUS4	CCC AGT CAC GAC GTT GTA AAA CGA TGG CAG CAA GGA CTC CTG	64° C.

F7-353-P	CAC ATG CCA CCC ACT ACC

F7-353RUS5	AGC GGA TAA CAA TTT CAC ACA GGT GAC GAT GCC CGT CAG GTA C	64° C.

[0310]

Masses

Allele Product Termination: ddG SEQ # Length Mass

F7-353-P atgccacccactacc 27 18 5333.6

353 CGG cacatgccacccactaccg 28 19 5646.8

353 CAG cacatgccacccactaccag 29 20 5960

US5-bio bio- agcggataacaatttcacacagg 30 23 7648.6
Conclusion [0311]
The above examples demonstrate an effect of altered frequency of disease causing genetic factors within the general population. Interpretation of those results allows prediction of the medical relevance of polymorphic genetic alterations. In addition, conclusions can be drawn with regard to their penetrance, diagnostic specificity, positive predictive value, onset of disease, most appropriate onset of preventive strategies, and the general applicability of genetic alterations identified in isolated populations to panmixed populations. Therefore, an age- and sex-stratified population-based sample bank that is ethnically homogenous is a suitable tool for rapid identification and validation of genetic factors regarding their potential medical utility. [0312]

EXAMPLE 3

Morbidity and Mortality Markers [0313]
Sample Band and Initial Screening [0314]
Healthy samples were obtained through the blood bank of San Bernardino, Calif. Donors signed prior to the blood collection a consent form and agreed that their blood will be used in genetic studies with regard to human aging. All samples were anomymized. Tracking back of samples is not possible. [0315]
Isolation of DNA from Blood Samples of a Healthy Donor Population [0316]
Blood is obtained from a donor by venous puncture and preserved with 1 mM EDTA pH 8.0. Ten milliliters of whole blood from each donor was centrifuged at 2000×g. One milliliter of the buffy coat was added to 9 milliters of 155 mM NH[0317] ₄Cl, 1 OmM KHCO₃, and 0.1 mM Na₂EDTA, incubated 10 minutes at room temperature and centrifuged for 10 minutes at 2000×g. The supernatant was removed, and the white cell pellet was washed in 155 mM NH₄Cl, 10 mM KHCO₃, and 0.1 mM Na₂EDTA and resuspended in 4.5 milliliters of 50 mM Tris, 5 mM EDTA, and 1% SDS. Proteins were precipitated from the cell lysate by 6M Ammonium Acetate, pH 7.3, and separated from the nucleic acid by centrifugation 3000×g. The nucleic acid was recovered from the supernatant by the addition of an equal volume of 100% isopropanol and centrifugation at 2000×g. The dried nucleic acid pellet was hydrated in lOmM Tris pH 7.6 and 1 mM Na2EDTA and stored at 4C.

In this study, samples were pooled as shown in Table 1. Both parents of the blood donors were of Caucasian origin.

TABLE 1


Pool ID	Sex	Age-range	# individuals

SP1	Female	18-39 years	276
SP2	Males	18-39 years	276
SP3	Females	60-69 years	184
SP4	Males	60-79 years	368

More than 400 SNPs were tested using all four pools. After one test run 34 assays were selected to be re-assayed at least once. Finally, 10 assays showed repeatedly differences in allele frequencies of several percent and, therefore, fulfilled the criteria to be tested using the individual samples. Average allele frequency and standard deviation is tabulated in Table 2.

TABLE 2


Assay ID	SP1	SP1-STD	SP2	SP2-STD	SP3	SP3-STD	SP4	SP4-STD

47861	0.457	0.028	0.433	0.042	0.384	0.034	0.380	0.015
47751	0.276	0.007	0.403	0.006	0.428	0.052	0.400	0.097
48319	0.676	0.013	0.627	0.018	0.755	0.009	0.686	0.034
48070	0.581	0.034	0.617	0.045	0.561	n.a.	0.539	0.032
49807	0.504	0.034	0.422	0.020	0.477	0.030	0.556	0.005
49534	0.537	0.017	0.503	n.a.	0.623	0.023	0.535	0.009
49733	0.560	0.006	0.527	0.059	0.546	0.032	0.436	0.016
49947	0.754	0.008	0.763	0.047	0.736	0.052	0.689	0.025
50128	0.401	0.022	0.363	0.001	0.294	0.059	0.345	0.013
63306	0.697	0.012	0.674	0.013	0.712	0.017	0.719	0.005

So far, 7 out of the 10 potential morbidity markers were fully analyzed. Additional information about genes in which these SNPs are located was gathered through publicly available databases, including Genbank. [0320]
AKAPS [0321]
Candidate morbidity and mortality markers include housekeeping genes, such as genes involved in signal transduction. Among such genes are the A-kinase anchoring proteins (AKAPs) genes, which participate in signal transduction pathways involving protein phosphorylation. Protein phosphorylation is an important mechanism for enzyme regulation and the transduction of extracellular signals across the cell membrane in eukaryotic cells. A wide variety of cellular substrates, including enzymes, membrane receptors, ion channels and transcription factors, can be phosphorylated in response to extracellular signals that interact with cells. A key enzyme in the phosphorylation of cellular proteins in response to hormones and neurotransmitters is cyclic AMP (cAMP)-dependent protein kinase (PKA). Upon activation by cAMP, PKA thus mediates a variety of cellular responses to such extracellular signals. An array of PKA isozymes are expressed in mammalian cells. The PKAs usually exist as inactive tetramers containing a regulatory (R) subunit dimer and two catalytic (C) subunits. Genes encoding three C subunits (Cα, Cβ and Cy) and four R subunits (RIα, RIβ, RIIα and RIIβ) have been identified [see Takio et al. (1982) [0322] Proc. Natl. Acad. Sci. U.S. A. 79:2544-2548; Lee et al. (1983) Proc. Natl. Acad. Sci. U.S. A. 80:3608-3612; Jahnsen et al. (1996) J. Biol. Chem. 261:12352-12361; Clegg et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85:3703-3707; and Scott (1991) Pharmacol. Ther. 50:123-145]. The type I (RI) α and type II (RII) α subunits are distributed ubiquitously, whereas RIβ and RIIβ are present mainly in brain [see. e.g., Miki and Eddy (1999) J. Biol. Chem. 274:29057-29062]. The type I PKA holoenzyme (RIα and RIβ) is predominantly cytoplasmic, whereas the majority of type II PKA (RIIα and RIIβ) associates with cellular structures and organelles [Scott (1991) Pharmacol. Ther. 50:123-1451. Many hormones and other signals act through receptors to generate cAMP which binds to the R subunits of PKA and releases and activates the C subunits to phosphorylate proteins. Because protein kinases and their substrates are widely distributed throughout cells, there are mechanisms in place in cells to localize protein kinase-mediated responses to different signals. One such mechanism involves subcellular targeting of PKAs through association with anchoring proteins, referred to as A-kinase anchoring proteins (AKAPs), that place PKAs in close proximity to specific organelles or cytoskelet al components and particular substrates thereby providing for more specific PKA interactions and localized responses [see, e.g., Scott et al. (1990) J. Biol. Chem. 265:21561-21566; Bregman et al. (1991) J. Biol. Chem. 266:7207-7213; and Miki and Eddy (1999) J. Biol. Chem. 274:29057-290621. Anchoring not only places the kinase close to the substrates, but also positions the PKA holoenzyme at sites where it can optimally respond to fluctuations in the second messenger cAMP [Mochly-Rosen (1995) Science 268:247-251; Faux and Scott (1996) Trends Biochem. Sci. 21:312-315; Hubbard and Cohen (1993) Trends Biochem. Sci. 18:172-177].
Up to 75% of type II PKA is localized to various intracellular sites through association of the regulatory subunit (RII) with AKAPs [see, e.g., Hausken et al. (1996) [0323] J. Biol. Chem. 271:29016-290221. RII subunits of PKA bind to AKAPs with nanomolar affinity [Carr et al. (1992) J. Biol. Chem. 267:13376-13382], and many AKAP-RII complexes have been isolated from cell extracts. RI subunits of PKA bind to AKAPs with only micromolar affinity [Burton et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94:11067-110721. Evidence of binding of a PKA RI subunit to an AKAP has been reported [Miki and Eddy (1998) J. Biol. Chem 273:34384-34390] in which RIα-specific and RIα/RIIα dual specificity PKA anchoring domains were identified on FSC1/AKAP82. Additional dual specific AKAPs, referred to as D-AKAP1 and D-AKAP2, which interact with the type I and type II regulatory subunits of PKA have also been reported [Huang et al. (1997) J. Biol. Chem. 272:8057-8064; Huang et al. (1997) Proc. Natl. Acad. Sci. U.S.A. 94:11184-11189].
More than 20 AKAPs have been reported in different tissues and species. Complementary DNAs (cDNAs) encoding AKAPs have been isolated from diverse species, ranging from [0324] Caenorhabditis elegans and Drosophilia to human [see, e.g., Colledge and Scott (1999) Trends Cell Biol. 9:216-2211. Regions within AKAPs that mediate association with RII subunits of PKA have been identified. These regions of approximately 10-18 amino acid residues vary substantially in primary sequence, but secondary structure predictions indicate that they are likely to form an amphipathic helix with hydrophobic residues aligned along one face of the helix and charged residues along the other [Carr et al. (1991) J. Biol. Chem. 266:14188-14192; Carr et al. (1992) J. Biol. Chem. 267:13376-13382]. Hydrophobic amino acids with a long aliphatic side chain, e.g., valine, leucine or isoleucine, can participate in binding to RII subunits [Glantz et al. (1993) J. Biol. Chem. 268:12796-12804].
Many AKAPs also have the ability to bind to multiple proteins, including other signaling enzymes. For example, AKAP79 binds to PKA, protein kinase C (PKC) and the protein phosphatase calcineurin (PP2B) [Coghlan et al. (1995) [0325] Science 267:108-112 and Klauck et al. (1996) Science 271:1589-15921. Therefore, the targeting of AKAP79 to neuronal postsynaptic membranes brings together enzymes with opposite catalytic activities in a single complex.
AKAPs thus serve as potential regulatory mechanisms that increase the selectivity and intensity of a cAMP-mediated response. There is a need, therefore, to identify and elucidate the structural and functional properties of AKAPs in order to gain a complete understanding of the important role these proteins μplay in the basic functioning of cells. [0326]
AKAP10 [0327]
The sequence of a human AKAP10 cDNA (also referred to as D-AKAP2) is available in the GenBank database, at accession numbers AF037439 (SEQ ID NO: 31) and NM 007202. The AKAP10 gene is located on [0328] chromosome 17.
The sequence of a mouse D-AKAP2 cDNA is also available in the GenBank database (see accession number AF021833). The mouse D-AKAP2 protein contains an RGS domain near the amino terminus that is characteristic of proteins that interact with Gα subunits and possess GTPase activating protein-like activity [Huang et al. (1997) [0329] Proc. Natl. Acad. Sci. U.S.A. 94:11184-11189]. The human AKAP10 protein also has sequences homologous to RGS domains. The carboxy-terminal 40 residues of the mouse D-AKAP2 protein are responsible for the interaction with the regulatory subunits of PKA. This sequence is fairly well conserved between the mouse D-AKAP2 and human AKAP10 proteins.
Polymorphisms of the Human AKAP10 Gene and Polymorphic AKAP10 Proteins [0330]
Polymorphisms of AKAP genes that alter gene expression, regulation, protein structure and/or protein function are more likely to have a significant effect on the regulation of enzyme (particularly PKA) activity, cellular transduction of signals and responses thereto and on the basic functioning of cells than polymorphisms that do not alter gene and/or protein function. Included in the polymorphic AKAPs provided herein are human AKAP10 proteins containing differing amino acid residues at position number 646. [0331]
Amino acid 646 of the human AKAP10 protein is located in the carboxy-terminal region of the protein within a segment that participates in the binding of R-subunits of PKAs. This segment includes the carboxy-[0332] terminal 40 amino acids.
The amino acid residue reported for position 646 of the human AKAP10 protein is an isoleucine. Polymorphic human AKAP10 proteins provided herein have the amino acid sequence but contain residues other than isoleucine at amino acid position 646 of the protein. In particular embodiments of the polymorphic human AKAP10 proteins provided herein, the amino acid at position 646 is a valine, leucine or phenylalanine residue. [0333]
An A to G Transition at Nucleotide 2073 of the Human AKAP10 Coding Sequence [0334]
As described herein, an allele of the human AKAP10 gene that contains a specific polymorphism at position 2073 of the coding sequence and thereby encodes a valine at position 646 has been detected in varying frequencies in DNA samples from younger and older segments of the human population. In this allele, the A at position 2073 of the AKAP10 gene coding sequence is changed from an A to a G, giving rise to an altered sequence in which the codon for amino acid 646 changes from ATT, coding for isoleucine, to GTT, coding for valine. [0335]
Morbidity Marker 1: Human Protein Kinase A Anchoring Protein (AKAP10-1) [0336]
PCR Amplification and BiomassPROBE assay detection of AKAP10-1 in a healthy donor population [0337]
PCR Amplification of Donor Population for [0338] AKAP 10
PCR primers were synthesized by OPERON using phosphoramidite chemistry. Amplification of the AKAP10 target sequence was carried out in single 50 μl PCR reaction with 100 ng-1 ug of pooled human genomic DNAs in a 50 μl PCR reaction. Individual DNA concentrations within the pooled samples were present in equal concentration with the final concentration ranging from 1-25 ng. Each reaction containing IX PCR buffer (Qiagen, Valencia, Calif.), 200 uM dNTPs, 1U Hotstar Taq polymerase (Qiagen, Valencia, Calif.), 4 mM MgCl[0339] ₂, and 25 pmol of the forward primer containing the universal primer sequence and the target specific sequence 5′-TCTCAATCATGTGCATTGAGG-3′(SEQ ID NO: 45), 2 pmol of the reverse primer 5′-AGCGGATAACAATTTCACACAGGGATCACACAGCCATCAGCAG-3′ (SEQ ID NO: 46), and 10 pmol of a biotinylated universal primer complementary to the 5′ end of the PCR amplicon 5′-AGCGGATAACAATTTCACACAGG-3′(SEQ ID NO: 47). After an initial round of amplification with the target with the specific forward and reverse primer, the 5′ biotinylated universal primer then hybridized and acted as a reverse primer thereby introducing a 3′ biotin capture moiety into the molecule. The amplification protocol results in a 5′-biotinylated double stranded DNA amplicon and dramatically reduces the cost of high throughput genotyping by eliminating the need to 5′ biotin label each forward primer used in a genotyping. Thermal cycling was performed in 0.2 mL tubes or 96 well plate using an MJ Research Thermal Cycler (calculated temperature) with the following cycling parameters: 94° C. for 5 min; 45 cycles: 94° C. for 20 sec, 56° C. for 30 sec, 72° C. for 60 sec; 72° C. 3 min.
Immobilization of DNA [0340]
The 50 μl PCR reaction was added to 25 ul of streptavidin coated magnetic bead (Dynal) prewashed three times and resuspended in 1M NH[0341] ₄Cl, 0.06M NH₄OH. The PCR amplicons were allowed to bind to the beads for 15 minutes at room temperature. The beads were then collected with a magnet and the supernatant containing unbound DNA was removed. The unbound strand was released from the double stranded amplicons by incubation in 100 mM NaOH and washing of the beads three times with 10 mM Tris pH 8.0.
BiomassPROBE Assay Analysis of Donor Population for AKAP10-1 (clone 48319) [0342]
Genotyping using the BiomassPROBE assay methods was carried out by resuspending the DNA coated magnetic beads in 26 mM Tris-HCl pH 9.5, 6.5 mM MgCl[0343] ₂and 50 mM each of dTTP and 50 mM each of ddCTP, ddATP, ddGTP, 2.5U of a thermostable DNA polymerase (Ambersham) and 20 pmol of a template specific oligonucleotide PROBE primer 5′-CTGGCGCCCACGTGGTCAA-3′ (SEQ ID NO: 48) (Operon). Primer extension occurs with three cycles of oligonucleotide primer hybridization and extension. The extension products were analyzed after denaturation from the template with 50 mM NH₄Cl and transfer of 150 nL each sample to a silicon chip preloaded with 150 nL of H3PA matrix material. The sample material was allowed to crystallize and was analyzed by MALDI-TOF (Bruker, PerSeptive). The SNP that is present in AKAP10-1 is a T to C transversion at nucleotide number 156277 of the sequence of a genomic clone of the AKAP10 gene (GenBank Accession No. AC005730) (SEQ ID NO: 36). SEQ ID NO: 35: represents the nucleotide sequence of human chromosome 17, which contains the genomic nucleotide sequence of the human AKAP10 gene, and SEQ ID NO: 36 represents the nucleotide sequence of human chromosome 17, which contains the genomic nucleotide sequence of the human AKAP10-1 allele. The mass of the primer used in the BioMass probe reaction was 5500.6 daltons. In the presence of the SNP, the primer is extended by the addition of ddC, which has a mass of 5773.8. The wildtype gene results in the addition of dT and ddG to the primer to produce an extension product having a mass of 6101 daltons.
The frequency of the SNP was measured in a population of age selected healthy individuals. Five hundred fifty-two (552) individuals between the ages of 18-39 years (276 females, 276 males) and 552 individuals between the ages of 60-79 (184 females between the ages of 60-69, 368 males between the age of 60-79) were tested for the presence of the polymorphism localized in the non-translated 3′ region of [0344] AKAP 10. Differences in the frequency of this polymorphism with increasing age groups were observed among healthy individuals. Statistical analysis showed that the significance level for differences in the allelic frequency for alleles between the “younger” and the “older” populations was p=0.0009 and for genotypes was p=0.003. Differences between age groups are significant. For the total population allele significance is p=0.0009, and genotype significance is p=0.003.
This marker led to the best significant result with regard to allele and genotype frequencies in the age-stratified population. FIG. 19 shows the allele and genotype frequency in both genders as well as in the entire population. For the latter, the significance for alleles was p=0.0009 and for genotypes was p=0.003. The young and old populations were in Hardy-Weinberg equilibrium. A preferential change of one particular genotype was not observed. [0345]
The polymorphism is localized in the non-translated 3′-region of the gene encoding the human protein kinase A anchoring protein (AKAP10). The gene is located on [0346] chromosome 17. Its structure includes 15 exons and 14 intervening sequences (introns). The encoded protein is responsible for the sub-cellular localization of the cAMP-dependent protein kinase and, therefore, plays a key role in the G-protein mediated receptor-signaling pathway (Huang et al. PNAS (1007) 94:11184-11189). Since its localization is outside the coding region, this polymorphism is most likely in linkage disequilibrium (LD) with other non-synonymous polymorphisms that could cause amino acid substitutions and subsequently alter the function of the protein. Sequence comparison of different Genbank database entries concerning this gene revealed further six potential polymorphisms of which two are supposed to change the respective amino acid (see Table 3).

TABLE 3

Exon Codon Nucleotides Amino acid

3 100 GCT > GCC Ala > Ala

4 177 AGT > GTG Met > Val

8 424 GGG > GGC Gly > Gly

10 524 CCG > CTG Pro > Leu

12 591 GTG > GTC Val > Val

12 599 CGC > CGA Arg > Arg
Morbitity Marker 2: Human Protein Kinase A Anchoring Protein (AKAP10-5) [0347]
Discovery of AKAP10-5 Allele (SEQ ID NO: 33) [0348]
Genomic DNA was isolated from blood (as described above) of seventeen (17) individuals with a genotype CC at the AKAP10-1 gene locus and a single heterozygous individual (CT) (as described). A target sequence in the AKAP10-1 gene which encodes the C-terminal PKA binding domain was amplified using the polymerase chain reaction. PCR primers were synthesized by OPERON using phosphoramidite chemistry. Amplification of the AKAP10-1 target sequence was carried out in individual 50 μl PCR reaction with 25 ng of human genomic DNA templates. Each reaction containing I×PCR buffer (Qiagen, Valencia, Calif.), 200 μM dNTPs, IU Hotstar Taq polymerase (Qiagen, Valencia, Calif.), 4 mM MgCl[0349] ₂, 25 pmol of the forward primer (Ex13F) containing the universal primer sequence and the target specific sequence 5′-TCC CAA AGT GCT GGA ATT AC-3′ (SEQ ID NO: 53), and 2 pmol of the reverse primer (Ex14R) 5′-GTC CAA TAT ATG CAA ACA GTT G-3′ (SEQ ID NO: 54). Thermal cycling was performed in 0.2 mL tubes or 96 well plate using an MJ Research Thermal Cycler (MJ Research, Waltham, Mass.) (calculated temperature) with the following cycling parameters: 94° C. for 5 min; 45 cycles; 94° C. for 20 sec, 56° C. for 30 sec, 72° C. for 60 sec; 72° C. 3 min. After amplification the amplicons were purified using a chromatography (Mo Bio Laboratories (Solana Beach, Calif.)).
The sequence of the 18 amplicons, representing the target region, was determined using a standard Sanger cycle sequencing method with 25 nmol of the PCR amplicon, 3.2 uM [0350] DNA sequencing primer 5′-CCC ACA GCA GTT AAT CCT TC-3′(SEQ ID NO: 55), and chain terminating dRhodamine labeled 2′, 3′ dideoxynucleotides (PE Biosystems, Foster City, Calif.) using the following cycling parameters: 96° C. for 15 seconds; 25 cycles: 55° C. for 15 seconds, 60° C. for 4 minutes. The sequencing products precipitated by 0.3M NaOAc and ethanol. The precipitate was centrifuged and dried. The pellets were resuspended in deionized formamide and separated on a 5% polyacrylimide gel. The sequence was determined using the “Sequencher” software (Gene Codes, Ann Arbor, Mich.).
The sequence of all 17 of the amplicons, which are homozygous for the AKAP10-1 SNP of the amplicons, revealed a polymorphism at nucleotide position 152171 (numbering for GenBank Accession No. AC005730 for AKAP10 genomic clone (SEQ ID NO: 35)) with A replaced by G. This SNP also can be designated as located at nucleotide 2073 of a cDNA clone of the wildtype AKAP10 (GenBank Accession No. AF037439) (SEQ ID NO: 31). The amino acid sequence of the human AKAP10 protein is provided as SEQ ID NO: 34. This single nucleotide polymorphism was designated as AKAP10-5 (SEQ ID NO: 33) and resulted in a substitution of a valine for an isoleucine residue at amino acid position 646 of the amino acid sequence of human AKAP10 (SEQ ID NO: 32). [0351]
PCR Amplification and BiomassPROBE Assay Detection of AKAP10-5 in a Healthy Donor Population [0352]
The healthy population stratified by age is a very efficient and a universal screening tool for morbidity associated genes by allowing for the detection of changes of allelic frequencies in the young compared to the old population. Individual samples of this healthy population base can be pooled to further increase the throughput. [0353]
Healthy samples were obtained through the blood bank of San Bernardino, Calif. Both parents of the blood donors were of Caucasian origin. Practically a healthy subject, when human, is defined as human donor who passes blood bank criteria to donate blood for eventual use in the general population. These criteria are as follows: free of detectable viral, bacterial, mycoplasma, and parasitic infections; not anemic; and then further selected based upon a questionnaire regarding history (see FIG. 3). Thus, a healthy population represents an unbiased population of sufficient health to donate blood according to blood bank criteria, and not further selected for any disease state. Typically such individuals are not taking any medications. [0354]
PCR primers were synthesized by OPERON using phosphoramidite chemistry. Amplification of the AKAP10 target sequence was carried out in a single 50 μl PCR reaction with 100 ng-1 μg of pooled human genomic DNAs in a 50 μl PCR reaction. Individual DNA concentrations within the pooled samples were present in equal concentration with the final concentration ranging from 1-25 ng. Each reaction contained 1×PCR buffer (Qiagen, Valencia, Calif.), 200 μM dNTPs, 1U Hotstar Taq polymerase (Qiagen, Valencia, Calif.), 4 mM MgCl[0355] ₂, and 25 pmol of the forward primer containing the universal primer sequence and the target specific sequence 5′-AGCGGATAACAATTTCACACAGGGAGCTAGCTTGGAAGAT TGC-3′ (SEQ ID NO: 41), 2 pmol of the reverse primer 5′-GTCCAATATATGCAAACAGTTG-3′ (SEQ ID NO: 54), and 10 pmol of a biotinylated universal primer complementary to the 5′ end of the PCR amplicon BIO:5′-AGCGGATAACAATTTCACACAGG-3′ (SEQ ID NO: 43). After an initial round of amplification with the target with the specific forward and reverse primer, the 5′ biotinylated universal primer can then be hybridized and acted as a forward primer thereby introducing a 5′ biotin capture moiety into the molecule. The amplification protocol resulted in a 5′-biotinylated double stranded DNA amplicon and dramatically reduced the cost of high throughput genotyping by eliminating the need to 5′ biotin label every forward primer used in a genotyping.
Themal cycling was performed in 0.2 mL tubes or 96 well plate using an MJ Research Thermal Cycler (calculated temperature) with the following cycling parameters: 94° C. for 5 min; 45 cycles: 94° C. for 20 sec, 56° C. for 30 sec; 72° C. for 60 sec; 72° C. 3 min. [0356]
Immobilization of DNA [0357]
The 50 μl PCR reaction was added to 25 μL of streptavidin coated magnetic beads (Dynal, Oslo, Norway), which were prewashed three times and resuspended in 1M NH[0358] ₄Cl, 0.06M NH₄OH. The 5′ end of one strand of the double stranded PCR amplicons were allowed to bind to the beads for 15 minutes at room temperature. The beads were then collected with a magnet, and the supernatant containing unbound DNA was removed. The hybridized but unbound strand was released from the double stranded amplicons by incubation in 100 mM NaOH and washing of the beads three times with 10 mM Tris pH 8.0.
Detection of AKAP10-5 using BiomassPROBE™ Assay [0359]
BiomassPROBE™ assay of primer extension analysis (see, U.S. Pat. No. 6,043,031) of donor population for AKAP 10-5 (SEQ ID NO: 33) was performed. Genotyping using these methods was carried out by resuspending the DNA coated magnetic beads in 26 mM Tris-HCL pH 9.5, 6.5 mM MgCl[0360] ₂, 50 mM dTTP, 50 mM each of ddCTP, ddATP, ddGTP, 2.5U of a thermostable DNA polymerase (Ambersham), and 20 pmol of a template specific oligonucleotide PROBE primer 5′-ACTGAGCCTGCTGCATAA-3′ (SEQ ID NO: 44) (Operon). Primer extension occurs with three cycles of oligonucleotide primer with hybridization and extension. The extension products were analyzed after denaturation from the template with 50 mM NH₄Cl and transfer of 150 nL of each sample to a silicon chip preloaded with 150 nl of H3PA matrix material. The sample material was allowed to crystallize and analyzed by MALDI-TOF (Bruker, PerSeptive). The primer has a mass of 5483.6 daltons. The SNP results in the addition of a ddC to the primer, giving a mass of 5756.8 daltons for the extended product. The wild type results in the addition a T and ddG to the primer giving a mass of 6101 daltons.

The frequency of the SNP was measured in a population of age selected healthy individuals. Seven hundred thirteen (713) individuals under 40 years of age (360 females, 353 males) and 703 individuals over 60 years of age (322 females, 381 males) were tested for the presence of the SNP, AKAP10-5 (SEQ ID NO: 33). Results are presented below in Table 4.

TABLE 4


AKAP10-5 (2073V) frequency comparison in 2 age groups

	<40	>60	delta G allele

Female	Alleles	*G	38.6	34.6	4.0
		*A	61.4	65.4
	Genotypes	G	13.9	11.8	2.1
		GA	49.4	45.7
		A	36.7	42.5
Male	Alleles	*G	41.4	37.0	4.4
		*A	58.6	63.0
	Genotypes	G	18.4	10.8	7.7
		GA	45.9	52.5
		A	35.7	36.7
Total	Alleles	*G	40.0	35.9	4.1
		*A	60.0	64.1
	Genotypes	G	16.1	11.2	4.9
		GA	47.7	49.4
		A	36.2	39.4

FIG. 20 graphically shows these results of allele and genotype distribution in the age and sex stratified Caucasian population. [0362]
Morbidity Marker 3: Human Methionine Sulfoxide Reductase A (msrA) [0363]
The age-related allele and genotype frequency of this marker in both genders and the entire population is shown in FIG. 21. The decrease of the homozygous CC genotype in the older male population is highly significant. [0364]
Methionine Sulfoxide Reductase A (#63306) [0365]
PCR Amplification and BiomassPROBE assay detection of the human methioine sulfoxide reductase A (h-msr-A) in a healthy donor population [0366]
PCR Amplification of Donor Population for h-msr-A [0367]
PCR primers were synthesized by OPERON using phosphoramidite chemistry. Amplification of the AKAP10 target sequence was carried out in single 50 μl PCR reaction with 100 ng-1 ug of pooled human genomic DNA templates in a 50 μl PCR reaction. Individual DNA concentrations within the pooled samples were present in an equal concentration with the final concentration ranging from 1-25 ng. Each reaction containing I X PCR buffer (Qiagen, Valencia, Calif.), 200 μM dNTPs, 1U Hotstar Taq polymerase (Qiagen, Valencia, Calif.), 4 mM MgCl[0368] ₂, 25 pmol of the forward primer containing the universal primer sequence and the target specific sequence 5′-TTTCTCTGCACAGAGAGGC-3′ (SEQ ID NO: 49), 2 pmol of the reverse primer 5′-AGCGGATAACAATTTCACACAGGGCTGAAATCCTTCGCTTTACC-3′ (SEQ ID NO: 50), and 10 pmol of a biotinylated universal primer complementary to the 5′ end of the PCR amplicon 5′-AGCGGATAACAATTTCACACAGG-3′ (SEQ ID NO: 51). After an initial round of amplification of the target with the specific forward and reverse primers, the 5′ biotinylated universal primer was then hybridized and acted as a reverse primer thereby introducing a 3′ biotin capture moiety into the molecule. The amplification protocol results in a 5′-biotinylated double stranded DNA amplicon and dramatically reduces the cost of high throughput genotyping by eliminating the need to 5′ biotin label each forward primer used in a genotyping. Thermal cycling was performed in 0.2 mL tubes or 96 well plate using an MJ Research Thermal Cycler (calculated temperature) with the following cycling parameters: 94° C. for 5 min; 45 cycles: 94° C. for 20 sec, 56° C. for 30 sec, 72° C. for 60 sec; 72° C. 3 min.
Immobilization of DNA [0369]
The 50 μl PCR reaction was added to 25 ul of streptavidin coated magnetic bead (Dynal) prewashed three times and resuspended in 1M NH[0370] ₄Cl, 0.06M NH₄OH. The PCR amplicons were allowed to bind to the beads for 15 minutes at room temperature. The beads were then collected with a magnet and the supernatant containing unbound DNA was removed. The unbound strand was released from the double stranded amplicons by incubation in 100 mM NaOH and washing of the beads three times with 10 mM Tris pH 8.0.
BiomassPROBE Assay Analysis of Donor Population for h-msr A [0371]
Genotyping using the BiomassPROBE assay methods was carried out by resuspending the DNA coated magnetic beads in 26 mM Tris-HCl pH 9.5, 6.5 mM MgCl[0372] ₂, 50 mM of dTTPs and 50 mM each of ddCTP, ddATP, ddGTP, 2.5U of a thermostable DNA polymerase (Ambersham), and 20 pmol of a template specific oligonucleotide PROBE primer 5′-CTGAAAAGGGAGAGAAAG-3′ (Operon) (SEQ ID NO: 52). Primer extension occurs with three cycles of oligonucleotide primer with hybridization and extension. The extension products were analyzed after denaturation from the template with 50 mM NH₄Cl and transfer of 150 nl each sample to a silicon chip preloaded with 150 nl of H3PA matrix material. The sample material was allowed to crystallize and analyzed by MALDI-TOF (Bruker, PerSeptive). The SNP is represented as a T to C tranversion in the sequence of two ESTs. The wild type is represented by having a T at position 128 of GenBank Accession No. AW 195104, which represents the nucleotide sequence of an EST which is a portion of the wild type human msrA gene (SEQ ID NO: 39). The SNP is presented as a C at position 129 of GenBank Accession No. AW 874187, which represents the nucleotide sequence of an EST which is a portion of an allele of the human msrA gene (SEQ ID NO: 40).
In a genomic sequence the SNP is represented as an A to G transversion. The primer utilized in the BioMass probe reaction had a mass of 5654.8 daltons. In the presence of the SNP the primer is extended by the incorporation of a ddC and has a mass of 5928. In the presence of the wildtype the primer is extended by adding a dT and a DDC to produce a mass of 6232.1 daltons. [0373]
The frequency of the SNP was measured in a population of age selected healthy individuals. Five hundred fifty-two (552) individuals between the ages of 18-39 years (276 females, 276 males and 552 individuals between the age of 60-79 (184 females between the ages of 60-69, 368 males between the age of 60-79) were tested for the presence of the polymorphism localized in the nontranslated 3′ region of h-msr-A. [0374]
Genotype difference between male age group among healthy individuals is significant. For the male population allele significance is p=0.0009 and genotype significance is p=0.003. The age-related allele and genotype frequency of this marker in both genders and the entire population is shown in FIG. 21. The decrease of the homozygous CC genotype in the older male population is highly significant. [0375]
The polymorphism is localized in the non-translated 3′-region of the gene encoding the human methionine sulfoxide reductase (h-msrA). The exact localization is 451 base pairs downstream the stop codon (TAA). It is likely that this SNP is in linkage disequilibrium (LD) with another polymorphism more upstream in the coding or promoter region; thus, it does not directly cause morbidity. The enzyme methionine sulfoxide reductase has been proposed to exhibit multiple biological functions. It can serve to repair oxidative protein damage but also play an important role in the regulation of proteins by activation or inactivation of their biological functions (Moskovitz et al. (1990) PNAS 95:14071-14075). It has also been shown that its activity is significantly reduced in brain tissues of Alzheimer patients (Gabbita et al., (1999) J. Neurochem 73:1660-1666). It is scientifically conceivable that proteins involved in the metabolism of reactive oxygen species are associated to disease. [0376]
Conclusion [0377]
The use of the healthy population provides for the identification of morbidity markers. The identification of proteins involved in the G-protein coupled signaling transduction pathway or in the detoxification of oxidative stress can be considered as convincing results. Further confirmation and validation of other potential polymorphisms already identified in silico in the gene encoding the human protein kinase A anchoring protein could even provide stronger association to morbidity and demonstrate that this gene product is a suitable pharmaceutical or diagnostic target. [0378]

EXAMPLE 4

MALDI-TOF Mass Spectrometry Analysis [0379]
All of the products of the enzyme assays listed below were analyzed by MALDI-TOF mass spectrometry. A diluted matrix solution (0.15 μL) containing of 10:1 3-hydroxypicolinic acid:ammonium citrate in 1:1 water:acetonitrile diluted 2.5-fold with water was pipetted onto a SpectroChip (Sequenom, Inc.) and was allowed to crystallize. Then, 0.15 μL of sample was added. A linear PerSeptive Voyager DE mass spectrometer or Bruker Biflex MALDI-TOF mass spectrometer, operating in positive ion mode, was used for the measurements. The sample plates were kept at 18.2 kV for 400 nm after each UV laser shot (approximate 250 laser shots total), and then the target voltage was raised to 20 kV. The original spectra were digitized at 500 MHz. [0380]

EXAMPLE 5

Sample Conditioning [0381]
Where indicated in the examples below, the products of the enzymatic digestions were purified with ZipTips (Millipore, Bedford, Mass.). The ZipTips were pre-wetted with 10 μL 50% acetonitrile and equilibrated 4 times with 10 μl 0.1 M TEAAc. The oligonucleotide fragments were bound to the C18 in the ZipTip material by continuous aspiration and dispension of each sample into the ZipTip. Each digested oligonucleotide was conditioned by washing with 10 μL 0.1 M TEAAc, followed by 4 washing steps with 10 μL H[0382] ₂O. DNA fragments were eluted from the Ziptip with 7 μL 50% acetonitrile.
Any method for condition the samples can be employed. Methods for conditioning, which generally is used to increase peak resolution, are well known (see, e.g., International PCT application No. WO 98/20019). [0383]

EXAMPLE 6

DNA Glycosylase-Mediated Sequence Analysis [0384]
DNA Glycosylases modifies DNA at each position that a specific nucleobase resides in the DNA, thereby producing abasic sites. In a subsequent reaction with another enzyme, a chemical, or heat, the phosphate backbone at each abasic site can be cleaved. [0385]
The glycosylase utilized in the following procedures was uracil-DNA glycosylase (UDG). Uracil bases were incorporated into DNA fragments in each position that a thymine base would normally occupy by amplifying a DNA target sequence in the presence of uracil. Each uracil substituted DNA amplicon was incubated with UDG, which cleaved each uracil base in the amplicon, and was then subjected to conditions that effected backbone cleavage at each abasic site, which produced DNA fragments. DNA fragments were subjected to MALDI-TOF mass spectrometry analysis. Genetic variability in the target DNA was then assessed by analyzing mass spectra. [0386]
Glycosylases specific for nucleotide analogs or modified nucleotides, as described herein, can be substituted for UDG in the following procedures. The glycosylase methods described hereafter, in conjunction with phosphate backbone cleavage and MALDI, can be used to analyze DNA fragments for the purposes of SNP scanning, bacteria typing, methylation analysis, microsatellite analysis, genotyping, and nucleotide sequencing and re-sequencing. [0387]
A. Genotyping [0388]
A glycosylase procedure was used to genotype the DNA sequence encoding UCP-2 (Uncoupling Protein 2). The sequence for UCP-2 is deposited in GenBank under accession number AF096289. The sequence variation genotyped in the following procedure was a cytosine (C-allele) to thymine (T-allele) variation at nucleotide position 4790, which results in a alanine to valine mutation at [0389] position 55 in the UCP-2 polypeptide.
DNA was amplified using a PCR procedure with a 50 μL reaction volume containing of 5 pmol biotinylated primer having the [0390] sequence 5′-TGCTTATCCCTGTAGCTACCCTGTCTTGGCCTTGCAGATCCAA-3′ (SEQ ID NO: 91), 15 pmol non-biotinylated primer having the sequence 5′-AGCGGATAACAATTTCACACAGGCCATCACACCGCGGTACTG-3′ (SEQ ID NO: 92), 200 μM dATP, 200 μM dCTP, 200 μM dGTP, 600 μM dUTP (to fully replace dTTP), 1.5 mM to 3 mM MgCl₂, 1 U of HotStarTaq polymerase, and 25 ng of CEPH DNA. Amplification was effected with 45 cycles at an annealing temperature of 56° C.
The amplification product was then immobilized onto a solid support by incubating 50 μL of the amplification reaction with 5 μL of prewashed Dynabeads for 20 minutes at room temperature. The supernatant was removed, and the beads were incubated with 50 μL of 0.1 M NaOH for 5 minutes at room temperature to denature the double-stranded PCR product in such a fashion that single-stranded DNA was linked to the beads. The beads were then neutralized by three washes with 50 μL 10 mM TrisHCl (pH 8). The beads were resuspended in 10 μL of a 60 mM TrisHCl/1 mM EDTA (pH 7.9) solution, and 1 U uracil DNA glycosylase was added to the solution for 45 minutes at 37° C. to remove uracil nucleotides present in the single-stranded DNA linked to the beads. The beads were then washed two times with 25 μL of 10 mM TrisHCl (pH 8) and once with 10 μL of water. The biotinylated strands were then eluted from the beads with 12 μL of 2 M NH[0391] ₄OH at 60° C. for 10 minutes. The backbone of the DNA was cleaved by incubating the samples for 10 min at 95° C. (with a closed lid), and ammonia was evaporated from the samples by incubating the samples for 11 min at 80° C.
The cleavage fragments were then analyzed by MALDI-TOF mass spectrometry as described in Example 4. The T-allele generated a unique fragment of 3254 Daltons. The C-allele generated a unique fragment of 4788 Daltons. These fragements were distinguishable in mass spectra. Thus, the above-identified procedure was successfully utilized to genotype individuals heterozygous for the C-allele and T-aliele in UCP-2. [0392]
B. Glycosylase Analysis Utilizing Pooled DNA Samples [0393]
The glycosylase assay was conducted using pooled samples to detect genetic variability at the UCP-2 locus. DNA of known genotype was pooled from eleven individuals and was diluted to a fixed concentration of 5 ng/μL. The procedure provided in Example 3A was followed using 2 pmol of forward primer having a sequence of 5′-CCCAGTCACGACGTTGTAAAACGTCTTGGCCTTGCAGATCCAAG-3′ (SEQ ID NO: 93) and 15 pmol of reverse primer having the [0394] sequence 5′-AGCGGATAACAATTTCACACAGGCCATCACACCGCGGTACTG-3′ (SEQ ID NO: 94). In addition, 5 pmol of biotinylated primer having the sequence 5′bioCCCAGTCACGACGTTGTAAAACG 3′ (SEQ ID NO: 97) can be introduced to the PCR reaction after about two cycles. The fragments were analyzed via MALDI-TOF mass spectroscopy (Example 4). As determined in Example 3A, the T-allele, which generated a unique fragment of 3254 Daltons, could be distinguished in mass spectra from the C-allele, which generated a unique fragment of 4788 Daltons. Allelic frequency in the pooled samples was quantified by integrating the area under each signal corresponding to an allelic fragment. Integration was accomplished by hand calculations using equations well known to those skilled in the art. In the pool of eleven samples, this procedure suggested that 40.9% of the individuals harbored the T allele and 59.09% of the individuals harbored the C allele.
C. Glycosylase-Mediated Microsatellite Analysis [0395]
A glycosylase procedure was utilized to identify microsatellites of the Bradykinin Receptor 2 (BKR-2) sequence. The sequence for BKR-2 is deposited in GenBank under accession number X86173. BKR-2 includes a SNP in the promoter region, which is a C to T variation, as well as a SNP in a repeated unit, which is a G to T variation. The procedure provided in Example 3A was utilized to identify the SNP in the promotor region, the SNP in the microsattelite repeat region, and the number of repeated units in the microsattelite region of BKR-2. Specifically, a forward PCR primer having the [0396] sequence 5′-CTCCAGCTGGGCAGGAGTGC-3′ (SEQ ID NO: 95) and a reverse primer having the sequence 5′-CACTTCAGTCGCTCCCT-3′ (SEQ ID NO: 96) were utilized to amplify BKR-2 DNA in the presence of uracil. The amplicon was fragmented by UDG followed by backbone cleavage. The cleavage fragments were analyzed by MALDI-TOF mass spectrometry as described in Example 4.
With regard to the SNP in the BKR-2 promotor region having a C to T variation, the C-allele generated a unique fragment having a mass of 7342.4 Daltons, and the T-allele generated a unique fragment having a mass of 7053.2 Daltons. These fragments were distinguishable in mass spectra. Thus, the above-identified procedure was successfully utilized to genotype individuals heterozygous for the C-allele and T-allele in the promotor region of BKR-2. [0397]
With regard to the SNP in the BKR-2 repeat region having a G to T variation, the T-allele generated a unique fragment having a mass of 1784 Daltons, which was readily detected in a mass spectrum. Hence, the presence of the T-allele was indicative of the G to T sequence variation in the repeat region of BKR-2. [0398]
In addition, the number of repeat regions was distinguished between individuals having two repeat sequences and individuals having three repeat sequences in BKR-2. The DNA of these individuals did not harbor the G to T sequence variation in the repeat sequence as each repeat sequence contained a G at the SNP locus. The number of repeat regions was determined in individual samples by calculating the area under a signal corresponding to a unique DNA fragment having a mass of 2771.6 Daltons. This signal in spectra generated from individuals having two repeat regions had an area that was thirty-three percent less than the area under the same signal in spectra generated from individuals having three repeat regions. Thus, the procedures discussed above can be utilized to genotype individuals for the number of repeat sequences present in BKR-2. [0399]
D. Bisulfite Treatment Coupled with Glycosylase Digestion [0400]
Bisulfite treatment of genomic DNA can be utilized to analyze positions of methylated cytosine residues within the DNA. Treating nucleic acids with bisulfite deaminates cytosine residues to uracil residues, while methylated cytosine remains unmodified. Thus, by comparing the sequence of a PCR product generated from genomic DNA that is not treated with bisulfite with the sequence of a PCR product generated from genomic DNA that is treated with bisulfite, the degree of methylation in a nucleic acid as well as the positions where cytosine is methylated can be deduced. [0401]
Genomic DNA (2 μg) was digested by incubation with 1 μL of a restriction enzyme at 37° C. for 2 hours. An aliquot of 3 M NaOH was added to yield a final concentration of 0.3M NaOH in the digestion solution. The reaction was incubated at 37° C. for 15 minutes followed by treatment with 5.35M urea, 4.44M bisulfite, and 10 mM hydroquinone, where the final concentration of hydroquinone is 0.5 mM. [0402]
The sample that was treated with bisulfite (sample A) was compared to the same digestion sample that had not undergone bisulfite treatment (sample B). After sample A was treated with bisulfite as described above, sample A and sample B were amplified by a standard PCR procedure. The PCR procedure included the step of overlaying each sample with mineral oil and then subjecting the sample to thermocycling (20 cycles of 15 minutes at 55° C. followed by 30 seconds at 95° C.). The PCR reaction contained four nucleotide bases, C, A, G, and U. The mineral oil was removed from each sample, and the PCR products were purified with glassmilk. Sodium iodide (3 volumes) and glassmilk (5 μL) were added to samples A and B. The samples were then placed on ice for 8 minutes, washed with 420 μL cold buffer, centrifuged for 10 seconds, and the supernatant fractions were removed. This process was repeated twice and then 25 μL of water was added. Samples were incubated for 5 minutes at 37° C., were centrifuged for 20 seconds, and the supernatant fraction was collected, and then this incubation/centrifugation/supernatant fraction collection procedure was repeated. 50 μL 0.1 M NaOH was then added to the samples to denature the DNA. The samples were incubated at room temperature for 5 minutes, washed three times with 50 μL of 10 mM TrisHCl (pH 8), and resuspended in 10 [0403] μL 60 mM TrisHCl/1 mM EDTA, pH 7.9.
The sequence of PCR products from sample A and sample B were then treated with 2U of UDG (MBI Fermentas) and then subjected to backbone cleavage, as described herein. The resulting fragments from each of sample A and sample B were analyzed by MALDI-TOF mass spectroscopy as described in Example 4. Sample A gave rise to a greater number of fragments than the number of fragments arising from sample B, indicative that the nucleic acid harbored at least one methylated cytosine moiety. [0404]

EXAMPLE 7

Fen-Ligase-Mediated Haplotyping [0405]
Haplotyping procedures permit the selection of a fragment from one of an individual's two homologous chromosomes and to genotype linked SNPs on that fragment. The direct resolution of haplotypes can yield increased information content, improving the diagnosis of any linked disease genes or identifying linkages associated with those diseases. In previous studies, haplotypes were typically reconstructed indirectly through pedigree analysis (in cases where pedigrees were available) through laborious and unreliable allele-specific PCR or through single-molecule dilution methods well known in the art. [0406]
A haplotyping procedure was used to determine the presence of two SNPs, referred to as SNP1 and SNP2, located on one strand in a DNA sample. The haplotyping procedure used in this assay utilized Fen-1, a site-specific “flap” endonuclease that cleaves DNA “flaps” created by the overlap of two oligonucleotides hybridized to a target DNA strand. The two overlapping oligonucleotides in this example were short arm and long arm allele-specific adaptors. The target DNA was an amplified nucleic acid that had been denatured and contained SNP1 and SNP2. [0407]
The short arm adaptor included a unique sequence not found in the target DNA. The 3′ distal nucleotide of the short arm adaptor was identical to one of the SNP1 alleles. Moreover, the long arm adaptor included two regions: a 3′ region complementary to the short arm and a 5′ gene-specific region complementary to the fragment of interest adjacent to the SNP. If there was a match between the adaptor and one of the homologues, the Fen enzyme recognized and cleaved the overlapping flap. The short arm of the adaptor was then ligated to the remainder of the target fragment (minus the SNP site). This ligated fragment was used as the forward primer for a second PCR reaction in which only the ligated homologue was amplified. The second PCR product (PCR2) was then analyzed by mass spectrometry. If there was no match between the adaptors and the target DNA, there was no overlap, no cleavage by Fen-1, and thus no PCR2 product of interest. [0408]
If there was more than one SNP in the sequence of interest, the second SNP (SNP2) was found by using an adaptor that was specific for SNP2 and hybridizing the adaptor to the PCR2 product containing the first SNP. The Fen-ligase and amplification procedures were repeated for the PCR2 product containing the first SNP. If the amplified product yielded a second SNP, then SNP1 and SNP2 were on the same fragment. [0409]
If the SNP is unknown, then four allele-specific adaptors (e.g. C, G, A, and T) can be used to hybridize with the target DNA. The substrates are then treated with the Fen-ligase protocol, including amplification. The PCR2 products can be analyzed by PROBE, as described herein, to determine which adaptors were hybridized to the DNA target and thus identify the SNPs in the sequence. [0410]
A Fen-ligase assay was used to detect two SNPs present in Factor VII. These SNPs are located 814 base pairs apart from each other. SNP1 was located at position 8401 (C to T), and SNP2 was located at 9215 (G to A). [0411]
A. First Amplification Step [0412]
A PCR product (PCR1) was generated for a known heterozygous individual at SNP1, a short distance from the 5′ end of the SNP. Specifically, a 10 μL PCR reaction was performed by mixing 1.5 mM MgCl[0413] ₂, 200 μM of each dNTP, 0.5 U HotStar polymerase, 0.1 μM of a forward primer having the sequence 5′-GCG CTC CTG TCG GTG CCA (SEQ ID NO: 56), 0.1 μM of a reverse primer having the sequence 5′-GCC TGA CTG GTG GGG CCC (SEQ ID NO: 57), and 1 ng of genomic DNA. The annealing temperature was 58° C., and the amplification process yielded fragments that were 861 bp in length.
The PCR1 reaction mixture was divided in half and was treated with an [0414] exonuclease 1/SAP mixture (0.22 μL mixture/5 μL PCR1 reaction) which contained 1.0 μL SAP and 0.1 μL exon1. The exonuclease treatment was done for 30 minutes at 37° C. and then 20 minutes at 85° C. to denature the DNA.
B. Adaptor Oligonucleotides [0415]
A solution of allele-specific adaptors (C and T), containing of one long and one short oligonucleotide per adaptor, was prepared. The long arm and short arm oligonucleotides of each adaptor (10 μM) were mixed in a 1:1 ratio and heated for 30 seconds at 95° C. The temperature was reduced in 2° C. increments to 37° C. for annealing. The C-adaptor had a short arm sequence of 5′-CAT GCA TGC ACG GTC (SEQ ID NO: 58) and a long arm sequence of 5′-CAG AGA GTA CCC CTC GAC CGT GCA TGC ATG (SEQ ID NO: 59). Hence, the long arm of the adaptor was 30 bp (15 bp gene-specific), and the short arm was 15 bp. The T-adaptor had a short arm sequence of 5′-CAT GCA TGC ACG GTT (SEQ ID NO: 60) and a long arm sequence of 5′-GTA CGT ACG TGC CAA CTC CCC ATG AGA GAC (SEQ ID NO: 61). The adaptor could also have a hairpin structure in which the short and long arm are separated by a loop containing of 3 to 10 nucleotides (SEQ ID NO: 118). [0416]
C. FEN-ligase Reaction [0417]
In two tubes (one tube for each allele-specific adaptor per sample) was placed a solution (Solution A) containing of 3.5 μl 10 mM 16% PEG/50 mM MOPS, 1.2 μl 25 mM MgCl[0418] ₂, 1.5 μl 10X Ampligase Buffer, and 2.5 μl PCR1. Each tube containing Solution A was incubated at 95° C. for 5 minutes to denature the PCR1 product. A second solution (Solution B) containing of 1.65 μl Ampligase (Thermostable ligase, Epicentre Technologies), 1.65 μl 200 ng/μl MFEN (from Methanocuccus jannaschil), and 3.0 μl of an allel specific adaptor (C or T) was prepared. Thus, different variations of Solution B, each variation containing of different allele-specific adaptors, were made. Solution B was added to Solution A at 95° C. and incubated at 55° C. for 3 hours. The total reaction volume was 15.0 μl per adaptor-specific reaction. For a bi-allelic system, 2×15.0 μl reactions were required.
The Fen-ligase reaction in each tube was then deactivated by adding 8.0 μl 10 mM EDTA. Then, 1.0 μl exoIII/Buffer (70%/30%) solution was added to each sample and incubated 30 minutes at 37° C., 20 minutes at 70° C. (to deactivate exoIII), and 5 minutes at 95° C. (to denature the sample and dissociate unused adaptor from template). The samples were cooled in an ice slurry and purified on UltraClean PCR Clean-up (MoBio) spin columns which removed all fragments less than 100 base pairs in length. The fragments were eluted with 50 μl H[0419] ₂O.
D. Second Amplification Step [0420]
A second amplification reaction (PCR2) was conducted in each sample tube using the short arm adaptor (C or T) sequence as the forward primer (minus the SNP1 site). Only the ligated homologue was amplified. A standard PCR reaction was conducted with a total volume of 10.0 μl containing of 1×Buffer (final concentration), 1.5 mM final concentration MgCl[0421] ₂, 200 μM final concentration dNTPs, 0.5 U HotStar polymerase, 0.1 μM final concentration forward primer 5′-CAT GCA TGC ACG GT (SEQ ID NO: 62), 0.1 μM final concentration reverse primer 5′-GCC TGA CTG GTG GGG CCC (SEQ ID NO: 63), and 1.0 μl of the purified FEN-ligase reaction solution. The annealing temperature was 58° C. The PCR2 product was analyzed by MALDI TOF mass spectroscopy as described in Example 4. The mass spectrum of Fen SNP1 showed a mass of 6084.08 Daltons, representing the C allele.
E. Genotyping Additional SNPs [0422]
The second SNP (SNP2) can be found by using an adaptor that is specific for SNP2 and hybridizing that adaptor to the PCR2 product containing the first SNP. The Fen-ligase and amplification procedures are repeated for the PCR2 product containing the first SNP. If the amplified product yields a second SNP, then SN1 and SN2 are on the same fragment. The mass spectrum of SNP2, representing the T allele, showed a mass of 6359.88 Daltons. [0423]
This assay also can be performed upon pooled DNA to yield haplotype frequencies as described herein. The Fen-ligase assay can be used to analyze multiplexes as described herein. [0424]

EXAMPLE 8

Nickase-Mediated Sequence Analysis [0425]
A DNA nickase, or DNase, was used to recognize and cleave one strand of a DNA duplex. NY2A nickase and NYS1 nickase (Megabase), which cleave DNA at the following sites: [0426]
NY2A: 5′ . . . R AG . . . 3′[0427]
3[0428] 40 . . . Y⇓TC . . . 5′ where R=A or G and Y=C or T
NYS1: 5′ . . . ⇓CC[A/G/T] . . . 3′[0429]
3′ . . . GG[T/C/A] . . . 5′[0430]
were used. [0431]
A. Nickase Digestion [0432]
Tris-HCl (10 mM), KCl (10 mM, pH 8.3), magnesium acetate (25 mM), BSA (1 mg/mL), and 6 U of Cvi NY2A or Cvi NYS1 Nickase (Megabase Research) were added to 25 pmol of double-stranded oligonucleotide template having a sequence of 5′-CGC AGG GTT TCC TCG TCG CAC TGG GCA TGT G-3′ (SEQ ID NO: 90, Operon, Alameda, Calif.) synthesized using standard phosphoramidite chemistry. With a total volume of 20 μL, the reaction mixture was incubated at 37° C. for 5 hours, and the digestion products were purified using ZipTips (Millipore, Bedford, Mass.) as described in Example 5. The samples were analyzed by MALDI-TOF mass spectroscopy as described in Example 1. The nickase Cvi NY2A yielded three fragments with masses 4049.76 Daltons, 5473.14 Daltons, and 9540.71 Daltons. The Cvi NYS1 nickase yielded fragments with masses 2063.18 Daltons, 3056.48 Daltons, 6492.81 Daltons, and 7450.14 Daltons. [0433]
B. Nickase Digestion of Pooled Samples [0434]
DQA (HLA ClassII-DQ Alpha, expected fragment size=225 bp) was amplified from the genomic DNA of 100 healthy individuals. DQA was amplified using standard PCR chemistry in a reaction having a total volume of 50 μL containing of 10 mM Tris-HCl, 10 mM KCl (pH 8.3), 2.5 mM MgCl[0435] ₂, 200 μM of each dNTP, 10 pmol of a forward primer having the sequence 5′-GTG CTG CAG GTG TAA ACT TGT ACC AG-3′(SEQ ID NO: 64), 10 pmol of a reverse primer having the sequence 5′-CAC GGA TCC GGT AGC AGC GGT AGA GTT G-3′(SEQ ID NO: 65), 1 U DNA polymerase (Stoffel fragment, Perkin Elmer), and 200 ng human genomic DNA (2 ng DNA/individual). The template was denatured at 94° C. for 5 minutes. Thermal cycling was continued with a touch-down program that included 45 cycles of 20 seconds at 94° C., 30 seconds at 56° C., 1 minute at 72° C., and a final extension of 3 minutes at 72° C. The crude PCR product was used in the subsequent nickase reaction.
The unpurified PCR product was subjected to nickase digestion. Tris-HCl (10 mM), KCl (10 mM, pH 8.3), magnesium acetate (25 mM), BSA (1 mg/mL), and 5 U of Cvi NY2A or Cvi NYS1 Nickase (Megabase Research) were added to 25 pmol of the amplified template with a total reaction volume of 20 μL. The mixture was then incubated at 37° C. for 5 hours. The digestion products were purified with either ZipTips (Millipore, Bedford, Mass.) as described in Example 5. The samples were analyzed by MALDI-TOF mass spectroscopy as described in Example 4. This assay also can be used to do multiplexing and standardless genotyping as described herein. [0436]
To simplify the nickase mass spectrum, the two complementary strands can be separated after digestion by using a single-stranded undigested PCR product as a capture probe. This probe (preparation shown below in Example 8C) can be hybridized to the nickase fragments in hybridization buffer containing 200 mM sodium citrate and 1% blocking reagent (Boehringer Mannheim). The reaction is heated to 95° C. for 5 minutes and cooled to room temperature over 30 minutes by using a thermal cycler (PTC-200 DNA engine, MJ Research, Waltham, Mass.). The capture probe-nickase fragment is immobilized on 140 μg of streptavidin-coated magnetic beads. The beads are subsequently washed three times with 70 mM ammonium citrate. The captured single-stranded nickase fragments are eluted by heating to 80° C. for 5 minutes in 5 μL of 50 mM ammonium hydroxide. [0437]
C. Preparation of Capture Probe [0438]
The capture probe is prepared by amplifying the human β-globin gene (3′ end of [0439] intron 1 to 5′ end of exon 2) via PCR methods in a total volume of 50 μL containing of GeneAmp 1XPCR Buffer II, 10 mM Tris-HCl, pH 8.3, 50 mM KCl, 2 mM MgCl₂, 0.2 mM dNTP mix, 10 pmol of each primer (forward primer 5′-ACTGGGCATGTGGAGACAG-3′(SEQ ID NO: 66) and biotinylated reverse primer bio5′-GCACTTTCTTGCCATGAG-3′(SEQ ID: 67), 2 U of AmpliTaq Gold, and 200 ng of human genomic DNA. The template is denatured at 94° C. for 8 minutes. Thermal cycling is continued with a touch-down program that included 11 cycles of 20 seconds at 94° C., 30 seconds at 64° C., 1 minute at 72° C.; and a final extension of 5 minutes at 72° C. The amplicon is purified using UltraClean™ PCR clean-up kit (MO Bio Laboratories, Solano Beach, Calif.).

EXAMPLE 9

Multiplex Type IIS SNP Assay [0440]
A Type IIS assay was used to identify human gene sequences with known SNPs. The Type IIS enzyme used in this assay was Fok I which effected double-stranded cleavage of the target DNA. The assay involved the steps of amplification and Fok I treatment of the amplicon. In the amplification step, the primers were designed so that each PCR product of a designated gene target was less than 100 bases such that a Fok I recognition sequence was incorporated at the 5′ and 3′ end of the amplicon. Therefore, the fragments that were cleaved by Fok I included a center fragment containing the SNP of interest. [0441]
Ten human gene targets with known SNPs were analyzed by this assay. Sequences of the ten gene targets, as well as the primers used to amplify the target regions, are found in Table 5. The ten targets were lipoprotein lipase, prothrombin, factor V, cholesterol ester transfer protein (CETP), factor VII, factor XIII, HLA-[0442] H exon 2, HLA-H exon 4, methylenetetrahydrofolate reductase (MTHR), and P53 exon 4 codon 72.
Amplification of the ten human gene sequences were carried out in a single 50 μL volume PCR reaction with 20 ng of human genomic DNA template in 5 PCR reaction tubes. Each reaction vial contained 1×PCR buffer (Qiagen), 200 μM dNTPs, 1 U Hotstar Taq polymerase (Qiagen), 4 mM MgCl[0443] ₂, and 10 pmol of each primer. US8, having sequence of 5′TCAGTCACGACGTT3′(SEQ ID NO: 68), and US9, having sequence of 5′CGGATAACAATTTC3′(SEQ ID NO: 69), were used for the forward and reverse primers respectively. Moreover, the primers were designed such that a Fok I recognition site was incorporated at the 5′ and 3′ ends of the amplicon. Thermal cycling was performed in 0.2 mL tubes or a 96 well plate using a MJ Research Thermal Cycler (calculated temperature) with the following cycling parameters: 94° C. for 5 minutes; 45 cycles: 94° C. for 20 seconds, 56° C. for 20 seconds, 72° C. for 60 seconds; and 72° C. for 3 minutes.

Following PCR, the sample was treated with 0.2 U Exonuclease I (Amersham Pharmacia) and S Alkaline Phosphotase (Amersham Pharmacia) to remove the unincorporated primers and dNTPs. Typically, 0.2 U of exonuclease I and SAP were added to 5 μL of the PCR sample. The sample was then incubated at 37° C. for 15 minutes. Exonuclease I and SAP were then inactivated by heating the sample up to 85° C. for 15 minutes. Fok I digestion was performed by adding 2 U of Fok I (New England Biolab) to the 5 uL PCR sample and incubating at 37° C. for 30 minutes. Since the Fok I restriction sites are located on both sides of the amplicon, the 5′ and 3′ cutoff fragments have higher masses than the center fragment containing the SNP. The sample was then purified by anion exchange and analyzed by MALDI-TOF mass spectrometry as described in Example 4. The masses of the gene fragments from this multiplexing experiment are listed in Table 6. These gene fragments were resolved in mass spectra thereby allowing multiplex analysis of sequence variability in these genes.

TABLE 5


Genes for Multiplex Type IIS Assay

		Seq. ID		Seq.
Gene	Sequence	No	Primers	ID No.

Lipoprotein	cctttgagaa agggctctgc ttgagttgta	98-99	5′	70
Lipase	gaaagaaccg ctgcaacaat		caatttcatcgctggatgcaatct
(Asn291Ser)	ctgggctatg agatca[a g]taa agtcagagcc		gggctatgagatc 3′
	aaaagaagca gcaaaatgta
			5′	71
			caatttcacacagcggatgcttct
			tttggctctgact 3′
Prothrombin	26731 gaattatttt tgtgtttcta aaactatggt	100-	5′	72
	tcccaataaa agtgactctc	101	tcagtcacgacgttggatgccaa
	26781 agc[g a]agcctc aatgctccca		taaaagtgactctcagc 3′
	gtgctattca tgggcagctc tctgggctca
			5′	73
			cggataacaatttcggatgcact
			gggagcattgaggc 3′
Factor V	taataggact acttctaatc tgtaagagca	102-	5′	74
(Arg506Gln)	gatccctgga caggc[g a]agga	103	tcagtcacgacgttggatgagca
			gatccctggacaggc 3′
	atacaggtat tttgtccttg aagtaacctt tcag		5′	75
			cggataacaatttcggatggaca
			aaatacctgtattcc 3′
Cholesterol ester	1261 ctcaccatgg gcatttgatt gcagagcage	104-	5′	76
transfer protein	tccgagtcc[g a] tccagagctt	105	tcagtcacgacgttggatgcaga
(CETP) (I405V)			gcagctccgagtc 3′
	1311 cctgcagtca atgatcaccg ctgtgggcat		5′	77
	ccctgaggtc atgtctcgta		cagcggtgatcattggatgcagg
			aagctctgg 3′
Factor VII	1221 agcaaggact cctgcaaggg ggacagtgga	106-	5′	78
(R353Q)	ggcccacatg ccacccacta	107	tcagtcacgacgttggatgccca
			catgccacccactac 3′
	1271 cc[a g]gggcacg tggtacctga		5′	79
	cgggcatcgt cagctggggc cagggctgcg		cggataacaatttcggatgcccg
			tcaggtaccacg 3′
Factor XIII	111 caataactct aatgcagcgg aagatgacct	108-	5′	80
(V34L)	gcccacagtg gagcttcagg	109	tcagtcacgacgttggatgccca
			cagtggagcttcag 3′
	161 gc[g t]tggtgcc ccggggcgtc		5′	81
	aacctgcaag gtatgagcat accccccttc		gctcataccttgcaggatgacg
			3′
HLA-H exon 2	361 ttgaagctttgggctacgtg gatgaccagc	110-	5′	82
(His63Asp)	tgttcgtgtt ctatgat[c g]at	111	tcagtcacgacgttggatgacca
			gctgttcgtgttc 3′
	411 gagagtcgcc gtgtggagcc ccgaactcca		5′	83
	tgggtttcca gtagaatttc		tacatggagttcggggatgcaca
			cggcgactctc 3′
HLA-H exon 4	1021 ggataacctt ggctgtaccc cctggggaag	112-	5′	84
(Cys282Tyr)	agcagagata tacgt[g a]ccag	113	tcagtcacgacgttggatgggga
			agagcagagatatacgt 3′
	1071 gtggagcacc caggcctgga tcagcccctc		5′	85
	attgtgatct gggagccctc		gaggggctgatccaggatgggt
			gctccac 3′
Methylentetra-	761 tgaagcactt gaagga gaag gtgtctgcgg	114-	5′	86
hydrofolate-	gag[c t]cgattt catcatcacg	115	tcagtcacgacgttggatgggga
redctase			agagcagagatatacgt 3′
(MTHR)
(Ala222Val)
	811 cagcttttct ttgaggctga cacattcttc		5′	87
			gaggggctgatccaggatgggt
			gctccac 3′
P53 Exon4	12101 tccagatgaa gctcccagaa	116-	5′	88
Codon 72	tgccagaggc tgctcccc[g c]c gtggcccctg	117	gatgaagctcccaggatgccag
(Arg72Pro)			aggc 3′
	12151 caccagcagc tcctacaccg		5′	89
	gcggcccctg		gccgccggtgtaggatgctgctg
			gtgc 3′

TABLE 6


The mass of Center Fragments for Ten Different SNP Typing by IIS Assay

Gene

LPL(^Asn291^Ser)

Prothrombin

FV(^Arg506^Gln)

CETP(^I405^V)

FVII(^R353^Q)

FXIII(^V34)

Genotype	A	G	G	A	G	A	G	A	G	A	G	T

+ strand	6213	6229	5845	5829	5677	5661	3388	3372	6128	6112	5058	5033
mass
(Da)
− strand	6129	6114	5949	5964	5472	5487	3437	3452	6174	6189	4916	4940
mass
(Da)

Gene

Hlah2

Hlah4

MTHR(^Ala222^Val)

P53exon4(^Arg72^Pro)

Genotype	C	G	G	A	C	T	G	C

+ strand	5889	5929	4392	4376	4400	4415	4586	4546
mass
(Da)
− strand	5836	5796	4319	4334	4368	4352	4724	4764
mass
(Da)

EXAMPLE 10

Exemplary use of Parental Medical History Parameter for Stratification of Healthy Datebase [0446]
A healthy database can be used to associate a disease state with a specific allele (SNP) that has been found to show a strong association between age and the allele, in particular the homozygous genotype. The method involves using the same healthy database used to identify the age dependent association, however stratification is by information given by the donors about common disorders from which their parents suffered (the donor's familial history of disease). There are three possible answers a donor could give about the health status of their parents: neither were affected, one was affected or both were affected. Only donors above a certain minimum age, depending on the disease, are utilized, as the donors parents must be old enough to to have exhibited clinical disease phenotypes. The genotype frequency in each of these groups is determined and compared with each other. If there is an association of the marker in the donor to a disease the frequency of the heterozyous genotype will be increased. The frequency of the homozygous genotype should not increase, as it should be significantly underrepresented in the healthy population. [0447]

EXAMPLE 11

Method and Device for Identifying a Biological Sample Description [0448]
A method and device for identifying a biological sample is provided. Referring now to FIG. 24, an [0449] apparatus 10 for identifying a biological sample is disclosed. The apparatus 10 for identifying a biological sample generally comprises a mass spectrometer 15 communicating with a computing device 20. In an embodiment, the mass spectrometer can be a MALDI-TOF mass spectrometer manufactured by Bruker-Franzen Analytik GmbH; however, it will be appreciated that other mass spectrometers can be substituted. The computing device 20 is typically a general purpose computing device. It will be appreciated that the computing device could be alternatively configured, for example, it can be integrated with the mass spectrometer or could be part of a computer in a larger network system.
The [0450] apparatus 10 for identifying a biological sample can operate as an automated identification system having a robot 25 with a robotic arm 27 configured to deliver a sample plate 29 into a receiving area 31 of the mass spectrometer 15. In such a manner, the sample to be identified can be placed on the plate 29 and automatically received into the mass spectrometer 15. The biological sample is then processed in the mass spectrometer to generate data indicative of the mass of DNA fragments in the biological sample. This data can be sent directly to computing device 20, or can have some preprocessing or filtering performed within the mass spectrometer. In an embodiment, the mass spectrometer 15 transmits unprocessed and unfiltered mass spectrometry data to the computing device 20. It will be appreciated that the analysis in the computing device can be adjusted to accommodate preprocessing or filtering performed within the mass spectrometer.
Referring now to FIG. 25, a [0451] general method 35 for identifying a biological sample is shown. In method 35, data are received into a computing device from a test instrument in block 40. Generally the data are received in a raw, unprocessed and unfiltered form, but alternatively can have some form of filtering or processing applied. The test instrument of an exemplary embodiment is a mass spectrometer as described above. It will be appreciated that other test instruments could be substituted for the mass spectrometer.
The data generated by the test instrument, and in particular the mass spectrometer, includes information indicative of the identification of the biological sample. More specifically, the data are indicative of the DNA composition of the biological sample. Typically, mass spectrometry data gathered from DNA samples obtained from DNA amplification techniques are noisier than, for example, those from typical protein samples. This is due in part because protein samples are more readily prepared in more abundance, and protein samples are more easily ionizable as compared to DNA samples. Accordingly, conventional mass spectrometer data analysis techniques are generally ineffective for DNA analysis of a biological sample. To improve the analysis capability so that DNA composition data can be more readily discerned, an embodiment uses wavelet technology for analyzing the DNA mass spectrometry data. Wavelets are an analytical tool for signal processing, numerical analysis, and mathematical modeling. Wavelet technology provides a basic expansion function which is applied to a data set. Using wavelet decomposition, the data set can be simultaneously analyzed in the time and frequency domains. Wavelet transformation is the technique of choice in the analysis of data that exhibit complicated time (mass) and frequency domain information, such as MALDI-TOF DNA data. Wavelet transforms as described herein have superior denoising properties as compared to conventional Fourier analysis techniques. Wavelet transformation has proven to be particularly effective in interpreting the inherently noisy MALDI-TOF spectra of DNA samples. In using wavelets, a “small wave” or “scaling function” is used to transform a data set into stages, with each stage representing a frequency component in the data set. Using wavelet transformation, mass spectrometry data can be processed, filtered, and analyzed with sufficient discrimination to be useful for identification of the DNA composition for a biological sample. [0452]
Referring again to FIG. 25, the data received in [0453] block 40 is denoised in block 45. The denoised data then has a baseline correction applied in block 50. A baseline correction is generally necessary as data coming from the test instrument, in particular a mass spectrometer instrument, has data arranged in a generally exponentially decaying manner. This generally exponential decaying arrangement is not due to the composition of the biological sample, but is a result of the physical properties and characteristics of the test instrument, and other chemicals involved in DNA sample preparation. Accordingly, baseline correction substantially corrects the data to remove a component of the data attributable to the test system, and sample preparation characteristics.
After denoising in [0454] block 45 and the baseline correction in block 50, a signal remains which is generally indicative of the composition of the biological sample. Due to the extraordinary discrimination required for analyzing the DNA composition of the biological sample, the composition is not readily apparent from the denoised and corrected signal. For example, although the signal can include peak areas, it is not yet clear whether these “putative” peaks actually represent a DNA composition, or whether the putative peaks are the result of a systemic or chemical aberration. Further, any call of the composition of the biological sample would have a probability of error which would be unacceptable for clinical or therapeutic purposes. In such critical situations, there needs to be a high degree of certainty that any call or identification of the sample is accurate. Therefore, additional data processing and interpretation is necessary before the sample can be accurately and confidently identified.
Since the quantity of data resulting from each mass spectrometry test is typically thousands of data points, and an automated system can be set to perform hundreds or even thousands of tests per hour, the quantity of mass spectrometry data generated is enormous. To facilitate efficient transmission and storage of the mass spectrometry data, block 55 shows that the denoised and baseline corrected data are compressed. [0455]
In one embodiment, the biological sample is selected and processed to have only a limited range of possible compositions. Accordingly, it is therefore known where peaks indicating composition should be located, if present. Taking advantage of knowing the location of these expected peaks, in [0456] block 60 the method 35 matches putative peaks in the processed signal to the location of the expected peaks. In such a manner, the probability of each putative peak in the data being an actual peak indicative of the composition of the biological sample can be determined. Once the probability of each peak is determined in block 60, then in block 65 the method 35 statistically determines the composition of the biological sample, and determines if confidence is high enough to calling a genotype.
Referring again to block 40, data are received from the test instrument, which can be a mass spectrometer. In a specific illustration, FIG. 26 shows an example of data from a mass spectrometer. The [0457] mass spectrometer data 70 generally comprises data points distributed along an x-axis 71 and a y-axis 72. The x-axis 71 represents the mass of particles detected, while the y-axis 72 represents a numerical concentration of the particles. As can be seen in FIG. 26, the mass spectrometry data 70 is generally exponentially decaying with data at the left end of the x-axis 73 generally decaying in an exponential manner toward data at the heavier end 74 of the x-axis 71. The general exponential presentation of the data is not indicative of the composition of the biological sample, but is more reflective of systematic error and characteristics. Further, as described above and illustrated in FIG. 26, considerable noise exists in the mass spectrometry DNA data 70.
Referring again to block 45, where the raw data received in [0458] block 40 is denoised, the denoising process will be described in more detail. As illustrated in FIG. 25, the denoising process generally entails 1) performing a wavelet transformation on the raw data to decompose the raw data into wavelet stage coefficients; 2) generating a noise profile from the highest stage of wavelet coefficients; and 3) applying a scaled noise profile to other stages in the wavelet transformation. Each step of the denoising process is further described below.
Referring now to FIG. 27, the wavelet transformation of the raw mass spectrometry data is generally diagramed. Using wavelet transformation techniques, the [0459] mass spectrometry data 70 is sequentially transformed into stages. In each stage, the data are represented in a high stage and a low stage, with the low stage acting as the input to the next sequential stage. For example, the mass spectrometry data 70 is transformed into stage 0 high data 82 and stage 0 low data 83. The stage 0 low data 83 is then used as an input to the next level transformation to generate stage 1 high data 84 and stage 1 low data 85. In a similar manner, the stage 1 low data 85 is used as an input to be transformed into stage 2 high data 86 and stage 2 low data 87. The transformation is continued until no more useful information can be derived by further wavelet transformation. For example, in the one embodiment a 24-point wavelet is used. More particularly a wavelet commonly referred to as the Daubechies 24 is used to decompose the raw data. It will be appreciated that other wavelets can be used for the wavelet transformation. Since each stage in a wavelet transformation has one-half the data points of the previous stage, the wavelet transformation can be continued until the stage n low data 89 has around 50 points. Accordingly, the stage n high 88 would contain about 100 data points. Since the exemplary wavelet is 24 points long, little data or information can be derived by continuing the wavelet transformation on a data set of around 50 points.
FIG. 28 shows an example of [0460] stage 0 high data 95. Since stage 0 high data 95 is generally indicative of the highest frequencies in the mass spectrometry data, stage 0 high data 95 will closely relate to the quantity of high frequency noise in the mass spectrometry data. In FIG. 29, an exponential fitting formula has been applied to the stage 0 high data 95 to generate a stage 0 noise profile 97. In particular, the exponential fitting formula is in the format A₀+A₁EXP (−A₂m). It will be appreciated that other exponential fitting formulae or other types of curve fits can be used.
Referring now to FIG. 30, noise profiles for the other high stages are determined. Since the later data points in each stage will likely be representative of the level of noise in each stage, only the later data points in each stage are used to generate a standard deviation figure that is representative of the noise content in that particular stage. More particularly, in generating the noise profile for each remaining stage, only the last five percent of the data points in each stage are analyzed to determined a standard deviation number. It will be appreciated that other numbers of points, or alternative methods could be used to generate such a standard deviation figure. [0461]
The standard deviation number for each stage is used with the [0462] stage 0 noise profile (the exponential curve) 97 to generate a scaled noise profile for each stage. For example, FIG. 30 shows that stage 1 high data 98 has stage 1 high data 103 with the last five percent of the data points represented by area 99. The points in area 99 are evaluated to determine a standard deviation number indicative of the noise content in stage 1 high data 103. The standard deviation number is then used with the stage 0 noise profile 97 to generate a stage 1 noise profile.
In a similar manner, [0463] stage 2 high 100 has stage 2 high data 104 with the last five percent of points represented by area 101. The data points in area 101 are then used to calculate a standard deviation number which is then used to scale the stage 0 noise profile 97 to generate a noise profile for stage 2 data. This same process is continued for each of the stage high data as shown by the stage n high 105. For stage n high 105, stage n high data 108 has the last five percent of data points indicated in area 106. The data points in area 106 are used to determine a standard deviation number for stage n. The stage n standard deviation number is then used with the stage 0 noise profile 97 to generate a noise profile for stage n. Accordingly, each of the high data stages has a noise profile.
FIG. 31 shows how the noise profile is applied to the data in each stage. Generally, the noise profile is used to generate a threshold which is applied to the data in each stage. Since the noise profile is already scaled to adjust for the noise content of each stage, calculating a threshold permits further adjustment to tune the quantity of noise removed. Wavelet coefficients below the threshold are ignored while those above the threshold are retained. Accordingly, the remaining data have a substantial portion of the noise content removed. [0464]
Due to the characteristics of wavelet transformation, the lower stages, such as [0465] stage 0 and 1, will have more noise content than the later stages such as stage 2 or stage n. Indeed, stage n low data are likely to have little noise at all. Therefore, in an embodiment, the noise profiles are applied more aggressively in the lower stages and less aggressively in the later stages. For example, FIG. 31 shows that stage 0 high threshold is determined by multiplying the stage 0 noise profile by a factor of four. In such a manner, significant numbers of data points in stage 0 high data 95 will be below the threshold and therefore eliminated. Stage 1 high threshold 112 is set at two times the noise profile for the stage 1 high data, and stage 2 high threshold 114 is set equal to the noise profile for stage 2 high. Following this geometric progression, stage n high threshold 116 is therefore determined by scaling the noise profile for each respective stage n high by a factor equal to (½^n-2). It will be appreciated that other factors can be applied to scale the noise profile for each stage. For example, the noise profile can be scaled more or less aggressively to accommodate specific systemic characteristics or sample compositions. As indicated above, stage n low data does not have a noise profile applied as stage n low data 118 is assumed to have little or no noise content. After the scaled noise profiles have been applied to each high data stage, the mass spectrometry data 70 has been denoised and is ready for further processing. A wavelet transformation of the denoised signal results in the sparse data set 120 as shown in FIG. 31.
Referring again to FIG. 25, the mass spectrometry data received in [0466] block 40 has been denoised in block 45 and is now passed to block 50 for baseline correction. Before performing baseline correction, the artifacts introduced by the wavelet transformation procedure can be removed. Wavelet transformation results vary slightly depending upon which point of the wavelet is used as a starting point. For example, an exemplary embodiment uses the 24-point Daubechies-24 wavelet. By starting the transformation at the 0 point of the wavelet, a slightly different result will be obtained than if starting at points 1 or 2 of the wavelet. Therefore, the denoised data are transformed using every available possible starting point, with the results averaged to determine a final denoised and shifted signal. For example, FIG. 33 shows that the wavelet coefficient is applied 24 different times and then the results averaged to generate the final data set. It will be appreciated that other techniques can be used to accommodate the slight error introduced due to wavelet shifting.
The formula 125 is generally indicated in FIG. 33. Once the signal has been denoised and shifted, a denoised and shifted [0467] signal 130 is generated as shown in FIG. 58. FIG. 34 shows an example of the wavelet coefficient 135 data set from the denoised and shifted signal 130.
FIG. 36 shows that [0468] putative peak areas 145, 147, and 149 are located in the denoised and shifted signal 150. The putative peak areas are systematically identified by taking a moving average along the signal 150 and identifying sections of the signal 150 which exceed a threshold related to the moving average. It will be appreciated that other methods can be used to identify putative peak areas in the signal 150.
[0469] Putative peak areas 145, 147 and 149 are removed from the signal 150 to create a peak-free signal 155 as shown in FIG. 37. The peak-free signal 155 is further analyzed to identify remaining minimum values 157, and the remaining minimum values 157 are connected to generate the peak-free signal 155.
FIG. 38 shows a process of using the peak-[0470] free signal 155 to generate a baseline 170 as shown in FIG. 39. As shown in block 162, a wavelet transformation is performed on the peak-free signal 155. All the stages from the wavelet transformation are eliminated in block 164 except for the n low stage. The n low stage will generally indicate the lowest frequency component of the peak-free signal 155 and therefore will generally indicate the system exponential characteristics. Block 166 shows that a signal is reconstructed from the n low coefficients and the baseline signal 170 is generated in block 168.
FIG. 39 shows a denoised and shifted data signal 172 positioned adjacent a [0471] correction baseline 170. The baseline correction 170 is subtracted from the denoised and shifted signal 172 to generate a signal 175 having a baseline correction applied as shown in FIG. 40. Although such a denoised, shifted, and corrected signal is sufficient for most identification purposes, the putative peaks in signal 175 are not identifiable with sufficient accuracy or confidence to call the DNA composition of a biological sample.
Referring again to FIG. 25, the data from the [0472] baseline correction 50 is now compressed in block 55; the compression technique used in an exemplary embodiment is detailed in FIG. 41. In FIG. 41the data in the baseline corrected data are presented in an array format 182 with x-axis points 183 having an associated data value 184. The x-axis is indexed by the non-zero wavelet coefficients, and the associated value is the value of the wavelet coefficient. In the illustrated data example in table 182, the maximum value 184 is indicated to be 1000. Although a particularly advantageous compression technique for mass spectrometry data is shown, it will be appreciated that other compression techniques can be used. The data also can be stored without compression.
In compressing the data according to one embodiment, an [0473] intermediate format 186 is generated. The intermediate format 186 generally comprises a real number having a whole number portion 188 and a decimal portion 190. The whole number portion is the x-axis point 183 while the decimal portion is the value data 184 divided by the maximum data value. For example, in the data 182 a data value “25” is indicated at x-axis point “100” . The intermediate value for this data point would be “100.025”.
From the intermediate [0474] compressed data 186 the final compressed data 195 is generated. The first point of the intermediate data file becomes the starting point for the compressed data. Thereafter each data point in the compressed data 195 is calculated as follows: the whole number portion (left of the decimal) is replaced by the difference between the current and the last whole number. The remainder (right of the decimal) remains intact. For example, the starting point of the compressed data 195 is shown to be the same as the intermediate data point which is “100.025”. The comparison between the first intermediate data point “100.025” and the second intermediate data point “150.220” is “50.220”. Therefore, “50.220” becomes the second point of the compressed data 195. In a similar manner, the second intermediate point is “150.220” and the third intermediate data point is “500.0001” . Therefore, the third compressed data becomes “350.000”. The calculation for determining compressed data points is continued until the entire array of data points is converted to a single array of real numbers.
FIG. 42 generally describes the method of compressing mass spectrometry data, showing that the data file in [0475] block 201 is presented as an array of coefficients in block 202. The data starting point and maximum is determined as shown in block 203, and the intermediate real numbers are calculated in block 204 as described above. With the intermediate data points generated, the compressed data are generated in block 205. The described compression method is highly advantageous and efficient for compressing data sets such as a processed data set from a mass spectrometry instrument. The method is particularly useful for data, such as mass spectrometry data, that uses large numbers and has been processed to have occasional lengthy gaps in x-axis data. Accordingly, an x-y data array for processed mass spectrometry data can be stored with an effective compression rate of 10×or more. Although the compression technique is applied to mass spectrometry data, it will be appreciated that the method can also advantageously be applied to other data sets.
Referring again to FIG. 25, peak heights are now determined in [0476] block 60. The first step in determining peak height is illustrated in FIG. 43 where the signal 210 is shifted left or right to correspond with the position of expected peaks. As the set of possible compositions in the biological sample is known before the mass spectrometry data are generated, the possible positioning of expected peaks is already known. These possible peaks are referred to as expected peaks, such as expected peaks 212, 214, and 216. Due to calibration or other errors in the test instrument data, the entire signal can be shifted left or right from its actual position, therefore, putative peaks located in the signal, such as putative peaks 218, 222, and 224 can be compared to the expected peaks 212, 214, and 216, respectively. The entire signal is then shifted such that the putative peaks align more closely with the expected peaks.
Once the putative peaks have been shifted to match expected peaks, the strongest putative peak is identified in FIG. 44. In one embodiment, the strongest peak is calculated as a combination of analyzing the overall peak height and area beneath the peak. For example, a moderately high but wide peak would be stronger than a very high peak that is extremely narrow. With the strongest putative peak identified, such as [0477] putative peak 225, a Gaussian 228 curve is fit to the peak 225. Once the Gaussian is fit, the width (W) of the Gaussian is determined and will be used as the peak width for future calculations.
As generally addressed above, the denoised, shifted, and baseline-corrected signal is not sufficiently processed for confidently calling the DNA composition of the biological sample. For example, although the baseline has generally been removed, there are still residual baseline effects present. These residual baseline effects are therefore removed to increase the accuracy and confidence in making identifications. [0478]
To remove the residual baseline effects, FIG. 45 shows that the [0479] putative peaks 218, 222, and 224 are removed from the baseline corrected signal. The peaks are removed by identifying a center line 230, 232, and 234 of the putative peaks 218, 222, and 224, respectively and removing an area to the left and to the right of the identified center line. For each putative peak, an area equal to twice the width (W) of the Gaussian is removed from the left of the center line, while an area equivalent to 50 daltons is removed from the right of the center line. It has been found that the area representing 50 daltons is adequate to sufficiently remove the effect of salt adducts which can be associated with an actual peak. Such adducts appear to the right of an actual peak and are a natural effect from the chemistry involved in acquiring a mass spectrum. Although a 50 Dalton buffer has been selected, it will be appreciated that other ranges or methods can be used to reduce or eliminate adduct effects.
The peaks are removed and remaining [0480] minima 247 located as shown in FIG. 46 with the minima 247 connected to create signal 245. A quartic polynomial is applied to signal 245 to generate a residual baseline 250 as shown in FIG. 47. The residual baseline 250 is subtracted from the signal 225 to generate the final signal 255 as indicated in FIG. 48. Although the residual baseline is the result of a quartic fit to signal 245, it will be appreciated that other techniques can be used to smooth or fit the residual baseline.
To determine peak height, as shown in FIG. 49, a Gaussian such as [0481] Gaussian 266, 268, and 270 is fit to each of the peaks, such as peaks 260, 262, and 264, respectively. Accordingly, the height of the Gaussian is determined as height 272, 274, and 276. Once the height of each Gaussian peak is determined, then the method of identifying a biological compound 35 can move into the genotyping phase 65 as shown in FIG. 25.
An indication of the confidence that each putative peak is an actual peak can be discerned by calculating a signal-to-noise ratio for each putative peak. Accordingly, putative peaks with a strong signal-to-noise ratio are generally more likely to be an actual peak than a putative peak with a lower signal-to-noise ratio. As described above and shown in FIG. 50, the height of each peak, such as [0482] height 272, 274, and 276, is determined for each peak, with the height being an indicator of signal strength for each peak. The noise profile, such as noise profile 97, is extrapolated into noise profile 280 across the identified peaks. At the center line of each of the peaks, a noise value is determined, such as noise value 282, 283, and 284. With a signal values and a noise values generated, signal-to-noise ratios can be calculated for each peak. For example, the signal-to-noise ratio for the first peak in FIG. 50 would be calculated as signal value 272 divided by noise value 282, and in a similar manner the signal-to-noise ratio of the middle peak in FIG. 50 would be determined as signal 274 divided by noise value 283.
Although the signal-to-noise ratio is generally a useful indicator of the presence of an actual peak, further processing has been found to increase the confidence by which a sample can be identified. For example, the signal-to-noise ratio for each peak in the exemplarly embodiment can be adjusted by the goodness of fit between a Gaussian and each putative peak. It is a characteristic of a mass spectrometer that sample material is detected in a manner that generally complies with a normal distribution. Accordingly, greater confidence will be associated with a putative signal having a Gaussian shape than a signal that has a less normal distribution. The error resulting from having a non-Gaussian shape can be referred to as a “residual error”. [0483]
Referring to FIG. 51, a residual error is calculated by taking a root mean square calculation between the Gaussian 293 and the [0484] putative peak 290 in the data signal. The calculation is performed on data within one width on either side of a center line of the Gaussian. The residual error is calculated as:
{square root}[(G−R)²/N],
where G is the Gaussian signal value, R is the putative peak value, and N is the number of points from −W to +W. The calculated residual error is used to generate an adjusted signal-to-noise ratio, as described below. [0485]
An adjusted signal noise ratio is calculated for each putative peak using the formula (S/N) * EXP[0486] ^(−1·R), where S/N is the signal-to-noise ratio, and R is the residual error determined above. Although the exemplary embodiment calculates an adjusted signal-to-noise ratio using a residual error for each peak, it will be appreciated that other techniques can be used to account for the goodness of fit between the Gaussian and the actual signal.
Referring now to FIG. 52, a probability is determined that a putative peak is an actual peak. In making the determination of peak probability, a [0487] probability profile 300 is generated where the adjusted signal-to-noise ratio is the x-axis and the probability is the y-axis. Probability is necessarily in the range between a 0% probability and a 100% probability, which is indicated as 1. Generally, the higher the adjusted signal-to-noise ratio, the greater the confidence that a putative peak is an actual peak.
At some target value for the adjusted signal-to-noise, it has been found that the probability is 100% that the putative peak is an actual peak and can confidently be used to identify the DNA composition of a biological sample. The target value of adjusted signal-to-noise ratio where the probability is assumed to be 100% is a variable parameter which is to be set according to application specific criteria. For example, the target signal-to-noise ratio will be adjusted depending upon trial experience, sample characteristics, and the acceptable error tolerance in the overall system. More specifically, for situations requiring a conservative approach where error cannot be tolerated, the target adjusted signal-to-noise ratio can be set to, for example, 10 and higher. Accordingly, 100% probability will not be assigned to a peak unless the adjusted signal-to-noise ratio is 10 or over. [0488]
In other situations, a more aggressive approach can be taken as sample data is more pronounced or the risk of error can be reduced. In such a situation, the system can be set to assume a 100% probability with a 5 or greater target signal-to-noise ratio. Of course, an intermediate signal-to-noise ratio target figure can be selected, such as 7, when a moderate risk of error can be assumed. Once the target adjusted signal-to-noise ratio is set for the method, then for any adjusted signal-to-noise ratio a probability can be determined that a putative peak is an actual peak. [0489]
Due to the chemistry involved in performing an identification test, especially a mass spectrometry test of a sample prepared by DNA amplifications, the allelic ratio between the signal strength of the highest peak and the signal strength of the second (or third and so on) highest peak should fall within an expected ratio. If the allelic ratio falls outside of normal guidelines, the exemplary embodiment imposes an allelic ratio penalty to the probability. For example, FIG. 53 shows an [0490] allelic penalty 315 which has an x-axis 317 that is the ratio between the signal strength of the second highest peak divided by signal strength of the highest peak. The yaxis 319 assigns a penalty between 0 and 1 depending on the determined allelic ratio. In the exemplary embodiment, it is assumed that allelic ratios over 30% are within the expected range and therefore no penalty is applied. Between a ratio of 10% and 30%, the penalty is linearly increased until at allelic ratios below 10% it is assumed the second-highest peak is not real. For allelic ratios between 10% and 30%, the allelic penalty chart 315 is used to determine a penalty 319, which is multiplied by the peak probability determined in FIG. 52 to determine a final peak probability. Although the exemplary embodiment incorporates an allelic ratio penalty to account for a possible chemistry error, it will be appreciated that other techniques can be used. Similar treatment will be applied to the other peaks.
With the peak probability of each peak determined, the statistical probability for various composition components can be determined, as an example, in order to determine the probability of each of three possible combinations of two peaks,—peak G, peak C and combinations GG, CC and GC. FIG. 54 shows an example where a most [0491] probable peak 325 is determined to have a final peak probability of 90%. Peak 325 is positioned such that it represents a G component in the biological sample. Accordingly, it can be maintained that there is a 90% probability that G exists in the biological sample. Also in the example shown in FIG. 54, the second highest probability is peak 330 which has a peak probability of 20%. Peak 330 is at a position associated with a C composition. Accordingly, it can be maintained that there is a 20% probability that C exists in the biological sample.
With the probability of G existing (90%) and the probability of C existing (20%) as a starting point, the probability of combinations of G and C existing can be calculated. For example, FIG. 54 indicates that the probability of GG existing 329 is calculated as 72%. This is calculated as the probability of GG is equal to the probability of G existing (90%) multiplied by the probability of C not existing (100% −20%). So if the probability of G existing is 90% and the probability of C not existing is 80%, the probability of GG is 72%. [0492]
In a similar manner, the probability of CC existing is equivalent to the probability of C existing (20%) multiplied by the probability of G not existing (100% −90%). As shown in FIG. 54, the probability of C existing is 20% while the probability of G not existing is 10%, so therefore the probability of CC is only 2%. Finally, the probability of GC existing is equal to the probability of G existing (90%) multiplied by the probability of C existing (20%). So if the probability of G existing is 90% and the probability of C existing is 20%, the probability of GC existing is 18%. In summary form, then, the probability of the composition of the biological sample is: [0493]

probability of GG: 72%;

probability of GC: 18%; and

probability of CC: 2%.
Once the probabilities of each of the possible combinations has been determined, FIG. 55 is used to decide whether or not sufficient confidence exists to call the genotype. FIG. 55 shows a [0494] call chart 335 which has an x-axis 337 which is the ratio of the highest combination probability to the second highest combination probability. The yaxis 339 simply indicates whether the ratio is sufficiently high to justify calling the genotype. The value of the ratio can be indicated by M 340. The value of M is set depending upon trial data, sample composition, and the ability to accept error. For example, the value M can be set relatively high, such as to a value 4 so that the highest probability must be at least four times greater than the second highest probability before confidence is established to call a genotype. If a certain level of error can be acceptable, the value of M can be set to a more aggressive value, such as to 3, so that the ratio between the highest and second highest probabilities needs to be only a ratio of 3 or higher. Of course, moderate value can be selected for M when a moderate risk can be accepted. Using the example of FIG. 54, where the probability of GG was 72% and the probability of GC was 18%, the ratio between 72% and 18% is 4.0, therefore, whether M is set to 3, 3.5, or 4, the system would call the genotype as GG. Although the exemplary embodiment uses a ratio between the two highest peak probabilities to determine if a genotype confidently can be called, it will be appreciated that other methods can be substituted. It will also be appreciated that the above techniques can be used for calculating probabilities and choosing genotypes (or more general DNA patterns) containing of combinations of more than two peaks.
Referring now to FIG. 56, a flow chart is shown generally defining the process of statistically calling genotype described above. In FIG. 56 [0495] block 402 shows that the height of each peak is determined and that in block 404 a noise profile is extrapolated for each peak. The signal is determined from the height of each peak in block 406 and the noise for each peak is determined using the noise profile in block 408. In block 410, the signal-to-noise ratio is calculated for each peak. To account for a non-Gaussian peak shape, a residual error is determined in block 412 and an adjusted signal-to-noise ratio is calculated in block 414. Block 416 shows that a probability profile is developed, with the probability of each peak existing found in block 418. An allelic penalty can be applied in block 420, with the allelic penalty applied to the adjusted peak probability in block 422. The probability of each combination of components is calculated in block 424 with the ratio between the two highest probabilities being determined in block 426. If the ratio of probabilities exceeds a threshold value then the genotype is called in block 428.
In another embodiment, the computing device 20 (FIG. 24) supports “standardless” genotyping by identifying data peaks that contain putative SNPs. Standardless genotyping is used, for example, where insufficient information is known about the samples to determine a distribution of expected peak locations, against which an allelic penalty as described above can be reliably calculated. This permits the computing device to be used for identification of peaks that contain putative SNPs from data generated by any assay that fragments a targeted DNA molecule. For such standardless genotyping, peaks that are associated with an area under the data curve that deviates significantly from the typical area of other peaks in the data spectrum are identified and their corresponding mass (location along the x-axis) is determined. [0496]
More particularly, peaks that deviate significantly from the average area of other peaks in the data are identified, and the expected allelic ratio between data peaks is defined in terms of the ratio of the area under the data peaks. Theoretically, where each genetic loci has the same molar concentration of analyte, the area under each corresponding peak should be the same, thus producing a 1.0 ratio of the peak area between any two peaks. In accordance with the methods provided herein, peaks having a smaller ratio relative to the other peaks in the data will not be recognized as peaks. More particularly, peaks having an area ratio smaller than 30% relative to a nominal value for peak area will be assigned an allelic penalty. The mass of the remaining peaks (their location along the x-axis of the data) will be determined based on oligonucleotide standards. [0497]
FIG. 57 shows a flow diagram representation of the processing by the computing device 20 (FIG. 24) when performing standardless genotyping. In the first operation, represented by the flow diagram box numbered 502, the computing device receives data from the mass spectrometer. Next, the height of each putative peak in the data sample is determined, as indicated by the [0498] block 504. After the height of each peak in the mass spectrometer data is determined, a de-noise process 505 is performed, beginning with an extrapolation of the noise profile (block 506), followed by finding the noise of each peak (block 508) and calculating the signal to noise ratio for each data sample (block 510). Each of these operations can be performed in accordance with the description above for denoise operations 45 of FIG. 25. Other suitable denoise operations will occur to those skilled in the art.
The next operation is to find the residual error associated with each data point. This is represented by the [0499] block 512 in FIG. 57. The next step, block 514, involves calculating an adjusted signal to noise ratio for each identified peak. A probability profile is developed next (block 516), followed by a determination of the peak probabilities at block 518. In an exemplary embodiment, the denoise operations of FIG. 57, comprising block 502 to block 518, comprise the corresponding operations described above in conjunction with FIG. 56 for block 402 through block 418, respectively.
The next action for the standardless genotype processing is to determine an allelic penalty for each peak, indicated by the [0500] block 524. As noted above, the standardless genotype processing of FIG. 57 determines an allelic penalty by comparing area under the peaks. Therefore, rather than compare signal strength ratios to determine an allelic penalty, such as described above for FIG. 53, the standardless processing determines the area under each of the identified peaks and compares the ratio of those areas. Determining the area under each peak can be computed using conventional numerical analysis techniques for calculating the area under a curve for experimental data.
Thus, the allelic penalty is assigned in accordance with FIG. 58, which shows that no penalty is assigned to peaks having a peak area relative to an expected average area value that is greater than 0.30 (30%). The allelic penalty is applied to the peak probability value, which can be determined according to the process such as described in FIG. 52. It should be apparent from FIG. 58 that the allelic penalty imposed for peaks below a ratio of 30% is that such peaks will be removed from further measurement and processing. Other penalty schemes, however, can be imposed in accordance with knowledge about the data being processed, as determined by those skilled in the art. [0501]
After the allelic penalty has been determined and applied, the standardless genotype processing compares the location of the remaining putative peaks to oligonucleotide standards to determine corresponding masses in the processing for [0502] block 524. For standardless genotype data, the processing of the block 524 is performed to determine mass and genotype, rather than performing the operations corresponding to block 424, 426, and 428 of FIG. 33. Techniques for performing such comparisons and determining mass will be known to those skilled in the art.
In another embodiment, the computing device 20 (FIG. 24) permits the detection and determination of the mass (location along the x-axis of the data) of the sense and antisense strand of fragments generated in the assay. If desired, the computing device can also detect and determine the quantity (area under each peak) of the respective sense and antisense strands, using a similar technique to that described above for standardless genotype processing. The data generated for each type of strand can then be combined to achieve a data redundancy and to thereby increase the confidence level of the determined genotype. This technique obviates primer peaks that are often observed in data from other diagnostic methods, thereby permitting a higher level of multiplexing. In addition, when quantitation is used in pooling experiments, the ratio of the measured peak areas is more reliably calculated than the peak identifying technique, due to data redundancy. [0503]
FIG. 23 is a flow diagram that illustrates the processing implemented by the [0504] computing device 20 to perform sense and antisense processing. In the first operation, represented by the flow diagram box numbered 602, the computing device receives data from the mass spectrometer. This data will include data for the sense strand and antisense strand of assay fragments. Next, the height of each putative peak in the data sample is determined, as indicated by the block 604. After the height of each peak in the mass spectrometer data is determined, a de-noise process 605 is performed, beginning with an operation that extrapolates the noise profile (block 606), followed by finding the noise of each peak (block 608) and calculating the signal to noise ratio for each data sample (block 610). Each of these operations can be performed in accordance with the description above for the denoise operations 45 of FIG. 25. Other suitable denoise operations will occur to those skilled in the art. The next operation is to find the residual error associated with each data point. This is represented by the block 612 in FIG. 36.
After the residual error for the data of the sense strand and antisense strand has been performed, processing to identify the genotypes will be performed for the sense strand and also for the antisense strand. Therefore, FIG. 23 shows that processing includes sense strand processing (block 630) and antisense strand processing (block 640). Each [0505] block 630, 640 includes processing that corresponds to adjusting the signal to noise ratio, developing a probability profile, determining an allelic penalty, adjusting the peak probability by the allelic penalty, calculating genotype probabilities, and testing genotype probability ratios, such as described above in conjunction with blocks 414 through 426 of FIG. 56. The processing of each block 630, 640 can, if desired, include standardless processing operations such as described above in conjunction with FIG. 57. The standardless processing can be included in place of or in addition to the processing operations of FIG. 56.
After the genotype probability processing is completed, the data from the sense strand and antisense strand processing is combined and compared to expected database values to obtain the benefits of data redundancy as between the sense strand and antisense strand. Those skilled in the art will understand techniques to take advantage of known data redundancies between a sense strand and antisense strand of assay fragments. This processing is represented by the [0506] block 650. After the data from the two strands is combined for processing, the genotype processing is performed (block 660) and the genotype is identified.
Since modifications will be apparent to those of skill in this art, it is intended that this invention be limited only by the scope of the appended claims. [0507]

0

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<211> LENGTH: 15

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Probe

<400> SEQUENCE: 27

atgccaccca ctacc 15

<210> SEQ ID NO 28

<211> LENGTH: 19

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Probe

<400> SEQUENCE: 28

cacatgccac ccactaccg 19

<210> SEQ ID NO 29

<211> LENGTH: 20

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Probe

<400> SEQUENCE: 29

cacatgccac ccactaccag 20

<210> SEQ ID NO 30

<211> LENGTH: 23

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Probe

<400> SEQUENCE: 30

agcggataac aatttcacac agg 23

<210> SEQ ID NO 31

<211> LENGTH: 2363

<212> TYPE: DNA

<213> ORGANISM: Homo Sapien

<220> FEATURE:

<221> NAME/KEY: CDS

<222> LOCATION: (138)...(2126)

<223> OTHER INFORMATION: AKAP-10

<300> PUBLICATION INFORMATION:

<308> DATABASE ACCESSION NUMBER: GenBank AF037439

<309> DATABASE ENTRY DATE: 1997-12-21

<400> SEQUENCE: 31

gcggcttgtt gataatatgg cggctggagc tgcctgggca tcccgaggag gcggtggggc 60

ccactcccgg aagaagggtc ccttttcgcg ctagtgcagc ggcccctctg gacccggaag 120

tccgggccgg ttgctga atg agg gga gcc ggg ccc tcc ccg cgc cag tcc 170

Met Arg Gly Ala Gly Pro Ser Pro Arg Gln Ser

1 5 10

ccc cgc acc ctc cgt ccc gac ccg ggc ccc gcc atg tcc ttc ttc cgg 218

Pro Arg Thr Leu Arg Pro Asp Pro Gly Pro Ala Met Ser Phe Phe Arg

15 20 25

cgg aaa gtg aaa ggc aaa gaa caa gag aag acc tca gat gtg aag tcc 266

Arg Lys Val Lys Gly Lys Glu Gln Glu Lys Thr Ser Asp Val Lys Ser

30 35 40

att aaa gct tca ata tcc gta cat tcc cca caa aaa agc act aaa aat 314

Ile Lys Ala Ser Ile Ser Val His Ser Pro Gln Lys Ser Thr Lys Asn

45 50 55

cat gcc ttg ctg gag gct gca gga cca agt cat gtt gca atc aat gcc 362

His Ala Leu Leu Glu Ala Ala Gly Pro Ser His Val Ala Ile Asn Ala

60 65 70 75

att tct gcc aac atg gac tcc ttt tca agt agc agg aca gcc aca ctt 410

Ile Ser Ala Asn Met Asp Ser Phe Ser Ser Ser Arg Thr Ala Thr Leu

80 85 90

aag aag cag cca agc cac atg gag gct gct cat ttt ggt gac ctg ggc 458

Lys Lys Gln Pro Ser His Met Glu Ala Ala His Phe Gly Asp Leu Gly

95 100 105

aga tct tgt ctg gac tac cag act caa gag acc aaa tca agc ctt tct 506

Arg Ser Cys Leu Asp Tyr Gln Thr Gln Glu Thr Lys Ser Ser Leu Ser

110 115 120

aag acc ctt gaa caa gtc ttg cac gac act att gtc ctc cct tac ttc 554

Lys Thr Leu Glu Gln Val Leu His Asp Thr Ile Val Leu Pro Tyr Phe

125 130 135

att caa ttc atg gaa ctt cgg cga atg gag cat ttg gtg aaa ttt tgg 602

Ile Gln Phe Met Glu Leu Arg Arg Met Glu His Leu Val Lys Phe Trp

140 145 150 155

tta gag gct gaa agt ttt cat tca aca act tgg tcg cga ata aga gca 650

Leu Glu Ala Glu Ser Phe His Ser Thr Thr Trp Ser Arg Ile Arg Ala

160 165 170

cac agt cta aac aca atg aag cag agc tca ctg gct gag cct gtc tct 698

His Ser Leu Asn Thr Met Lys Gln Ser Ser Leu Ala Glu Pro Val Ser

175 180 185

cca tct aaa aag cat gaa act aca gcg tct ttt tta act gat tct ctt 746

Pro Ser Lys Lys His Glu Thr Thr Ala Ser Phe Leu Thr Asp Ser Leu

190 195 200

gat aag aga ttg gag gat tct ggc tca gca cag ttg ttt atg act cat 794

Asp Lys Arg Leu Glu Asp Ser Gly Ser Ala Gln Leu Phe Met Thr His

205 210 215

tca gaa gga att gac ctg aat aat aga act aac agc act cag aat cac 842

Ser Glu Gly Ile Asp Leu Asn Asn Arg Thr Asn Ser Thr Gln Asn His

220 225 230 235

ttg ctg ctt tcc cag gaa tgt gac agt gcc cat tct ctc cgt ctt gaa 890

Leu Leu Leu Ser Gln Glu Cys Asp Ser Ala His Ser Leu Arg Leu Glu

240 245 250

atg gcc aga gca gga act cac caa gtt tcc atg gaa acc caa gaa tct 938

Met Ala Arg Ala Gly Thr His Gln Val Ser Met Glu Thr Gln Glu Ser

255 260 265

tcc tct aca ctt aca gta gcc agt aga aat agt ccc gct tct cca cta 986

Ser Ser Thr Leu Thr Val Ala Ser Arg Asn Ser Pro Ala Ser Pro Leu

270 275 280

aaa gaa ttg tca gga aaa cta atg aaa agt ata gaa caa gat gca gtg 1034

Lys Glu Leu Ser Gly Lys Leu Met Lys Ser Ile Glu Gln Asp Ala Val

285 290 295

aat act ttt acc aaa tat ata tct cca gat gct gct aaa cca ata cca 1082

Asn Thr Phe Thr Lys Tyr Ile Ser Pro Asp Ala Ala Lys Pro Ile Pro

300 305 310 315

att aca gaa gca atg aga aat gac atc ata gca agg att tgt gga gaa 1130

Ile Thr Glu Ala Met Arg Asn Asp Ile Ile Ala Arg Ile Cys Gly Glu

320 325 330

gat gga cag gtg gat ccc aac tgt ttc gtt ttg gca cag tcc ata gtc 1178

Asp Gly Gln Val Asp Pro Asn Cys Phe Val Leu Ala Gln Ser Ile Val

335 340 345

ttt agt gca atg gag caa gag cac ttt agt gag ttt ctg cga agt cac 1226

Phe Ser Ala Met Glu Gln Glu His Phe Ser Glu Phe Leu Arg Ser His

350 355 360

cat ttc tgt aaa tac cag att gaa gtg ctg acc agt gga act gtt tac 1274

His Phe Cys Lys Tyr Gln Ile Glu Val Leu Thr Ser Gly Thr Val Tyr

365 370 375

ctg gct gac att ctc ttc tgt gag tca gcc ctc ttt tat ttc tct gag 1322

Leu Ala Asp Ile Leu Phe Cys Glu Ser Ala Leu Phe Tyr Phe Ser Glu

380 385 390 395

tac atg gaa aaa gag gat gca gtg aat atc tta caa ttc tgg ttg gca 1370

Tyr Met Glu Lys Glu Asp Ala Val Asn Ile Leu Gln Phe Trp Leu Ala

400 405 410

gca gat aac ttc cag tct cag ctt gct gcc aaa aag ggg caa tat gat 1418

Ala Asp Asn Phe Gln Ser Gln Leu Ala Ala Lys Lys Gly Gln Tyr Asp

415 420 425

gga cag gag gca cag aat gat gcc atg att tta tat gac aag tac ttc 1466

Gly Gln Glu Ala Gln Asn Asp Ala Met Ile Leu Tyr Asp Lys Tyr Phe

430 435 440

tcc ctc caa gcc aca cat cct ctt gga ttt gat gat gtt gta cga tta 1514

Ser Leu Gln Ala Thr His Pro Leu Gly Phe Asp Asp Val Val Arg Leu

445 450 455

gaa att gaa tcc aat atc tgc agg gaa ggt ggg cca ctc ccc aac tgt 1562

Glu Ile Glu Ser Asn Ile Cys Arg Glu Gly Gly Pro Leu Pro Asn Cys

460 465 470 475

ttc aca act cca tta cgt cag gcc tgg aca acc atg gag aag gtc ttt 1610

Phe Thr Thr Pro Leu Arg Gln Ala Trp Thr Thr Met Glu Lys Val Phe

480 485 490

ttg cct ggc ttt ctg tcc agc aat ctt tat tat aaa tat ttg aat gat 1658

Leu Pro Gly Phe Leu Ser Ser Asn Leu Tyr Tyr Lys Tyr Leu Asn Asp

495 500 505

ctc atc cat tcg gtt cga gga gat gaa ttt ctg ggc ggg aac gtg tcg 1706

Leu Ile His Ser Val Arg Gly Asp Glu Phe Leu Gly Gly Asn Val Ser

510 515 520

ccg act gct cct ggc tct gtt ggc cct cct gat gag tct cac cca ggg 1754

Pro Thr Ala Pro Gly Ser Val Gly Pro Pro Asp Glu Ser His Pro Gly

525 530 535

agt tct gac agc tct gcg tct cag tcc agt gtg aaa aaa gcc agt att 1802

Ser Ser Asp Ser Ser Ala Ser Gln Ser Ser Val Lys Lys Ala Ser Ile

540 545 550 555

aaa ata ctg aaa aat ttt gat gaa gcg ata att gtg gat gcg gca agt 1850

Lys Ile Leu Lys Asn Phe Asp Glu Ala Ile Ile Val Asp Ala Ala Ser

560 565 570

ctg gat cca gaa tct tta tat caa cgg aca tat gcc ggg aag atg aca 1898

Leu Asp Pro Glu Ser Leu Tyr Gln Arg Thr Tyr Ala Gly Lys Met Thr

575 580 585

ttt gga aga gtg agt gac ttg ggg caa ttc atc cgg gaa tct gag cct 1946

Phe Gly Arg Val Ser Asp Leu Gly Gln Phe Ile Arg Glu Ser Glu Pro

590 595 600

gaa cct gat gta agg aaa tca aaa gga tcc atg ttc tca caa gct atg 1994

Glu Pro Asp Val Arg Lys Ser Lys Gly Ser Met Phe Ser Gln Ala Met

605 610 615

aag aaa tgg gtg caa gga aat act gat gag gcc cag gaa gag cta gct 2042

Lys Lys Trp Val Gln Gly Asn Thr Asp Glu Ala Gln Glu Glu Leu Ala

620 625 630 635

tgg aag att gct aaa atg ata gtc agt gac att atg cag cag gct cag 2090

Trp Lys Ile Ala Lys Met Ile Val Ser Asp Ile Met Gln Gln Ala Gln

640 645 650

tat gat caa ccg tta gag aaa tct aca aag tta tga ctcaaaactt 2136

Tyr Asp Gln Pro Leu Glu Lys Ser Thr Lys Leu *

655 660

gagataaagg aaatctgctt gtgaaaaata agagaacttt tttcccttgg ttggattctt 2196

caacacagcc aatgaaaaca gcactatatt tctgatctgt cactgttgtt tccagggaga 2256

gaatggggag acaatcctag gacttccacc ctaatgcagt tacctgtagg gcataattgg 2316

atggcacatg atgtttcaca cagtgaggag tctttaaagg ttaccaa 2363

<210> SEQ ID NO 32

<211> LENGTH: 662

<212> TYPE: PRT

<213> ORGANISM: Homo Sapien

<400> SEQUENCE: 32

Met Arg Gly Ala Gly Pro Ser Pro Arg Gln Ser Pro Arg Thr Leu Arg

1 5 10 15

Pro Asp Pro Gly Pro Ala Met Ser Phe Phe Arg Arg Lys Val Lys Gly

20 25 30

Lys Glu Gln Glu Lys Thr Ser Asp Val Lys Ser Ile Lys Ala Ser Ile

35 40 45

Ser Val His Ser Pro Gln Lys Ser Thr Lys Asn His Ala Leu Leu Glu

50 55 60

Ala Ala Gly Pro Ser His Val Ala Ile Asn Ala Ile Ser Ala Asn Met

65 70 75 80

Asp Ser Phe Ser Ser Ser Arg Thr Ala Thr Leu Lys Lys Gln Pro Ser

85 90 95

His Met Glu Ala Ala His Phe Gly Asp Leu Gly Arg Ser Cys Leu Asp

100 105 110

Tyr Gln Thr Gln Glu Thr Lys Ser Ser Leu Ser Lys Thr Leu Glu Gln

115 120 125

Val Leu His Asp Thr Ile Val Leu Pro Tyr Phe Ile Gln Phe Met Glu

130 135 140

Leu Arg Arg Met Glu His Leu Val Lys Phe Trp Leu Glu Ala Glu Ser

145 150 155 160

Phe His Ser Thr Thr Trp Ser Arg Ile Arg Ala His Ser Leu Asn Thr

165 170 175

Met Lys Gln Ser Ser Leu Ala Glu Pro Val Ser Pro Ser Lys Lys His

180 185 190

Glu Thr Thr Ala Ser Phe Leu Thr Asp Ser Leu Asp Lys Arg Leu Glu

195 200 205

Asp Ser Gly Ser Ala Gln Leu Phe Met Thr His Ser Glu Gly Ile Asp

210 215 220

Leu Asn Asn Arg Thr Asn Ser Thr Gln Asn His Leu Leu Leu Ser Gln

225 230 235 240

Glu Cys Asp Ser Ala His Ser Leu Arg Leu Glu Met Ala Arg Ala Gly

245 250 255

Thr His Gln Val Ser Met Glu Thr Gln Glu Ser Ser Ser Thr Leu Thr

260 265 270

Val Ala Ser Arg Asn Ser Pro Ala Ser Pro Leu Lys Glu Leu Ser Gly

275 280 285

Lys Leu Met Lys Ser Ile Glu Gln Asp Ala Val Asn Thr Phe Thr Lys

290 295 300

Tyr Ile Ser Pro Asp Ala Ala Lys Pro Ile Pro Ile Thr Glu Ala Met

305 310 315 320

Arg Asn Asp Ile Ile Ala Arg Ile Cys Gly Glu Asp Gly Gln Val Asp

325 330 335

Pro Asn Cys Phe Val Leu Ala Gln Ser Ile Val Phe Ser Ala Met Glu

340 345 350

Gln Glu His Phe Ser Glu Phe Leu Arg Ser His His Phe Cys Lys Tyr

355 360 365

Gln Ile Glu Val Leu Thr Ser Gly Thr Val Tyr Leu Ala Asp Ile Leu

370 375 380

Phe Cys Glu Ser Ala Leu Phe Tyr Phe Ser Glu Tyr Met Glu Lys Glu

385 390 395 400

Asp Ala Val Asn Ile Leu Gln Phe Trp Leu Ala Ala Asp Asn Phe Gln

405 410 415

Ser Gln Leu Ala Ala Lys Lys Gly Gln Tyr Asp Gly Gln Glu Ala Gln

420 425 430

Asn Asp Ala Met Ile Leu Tyr Asp Lys Tyr Phe Ser Leu Gln Ala Thr

435 440 445

His Pro Leu Gly Phe Asp Asp Val Val Arg Leu Glu Ile Glu Ser Asn

450 455 460

Ile Cys Arg Glu Gly Gly Pro Leu Pro Asn Cys Phe Thr Thr Pro Leu

465 470 475 480

Arg Gln Ala Trp Thr Thr Met Glu Lys Val Phe Leu Pro Gly Phe Leu

485 490 495

Ser Ser Asn Leu Tyr Tyr Lys Tyr Leu Asn Asp Leu Ile His Ser Val

500 505 510

Arg Gly Asp Glu Phe Leu Gly Gly Asn Val Ser Pro Thr Ala Pro Gly

515 520 525

Ser Val Gly Pro Pro Asp Glu Ser His Pro Gly Ser Ser Asp Ser Ser

530 535 540

Ala Ser Gln Ser Ser Val Lys Lys Ala Ser Ile Lys Ile Leu Lys Asn

545 550 555 560

Phe Asp Glu Ala Ile Ile Val Asp Ala Ala Ser Leu Asp Pro Glu Ser

565 570 575

Leu Tyr Gln Arg Thr Tyr Ala Gly Lys Met Thr Phe Gly Arg Val Ser

580 585 590

Asp Leu Gly Gln Phe Ile Arg Glu Ser Glu Pro Glu Pro Asp Val Arg

595 600 605

Lys Ser Lys Gly Ser Met Phe Ser Gln Ala Met Lys Lys Trp Val Gln

610 615 620

Gly Asn Thr Asp Glu Ala Gln Glu Glu Leu Ala Trp Lys Ile Ala Lys

625 630 635 640

Met Ile Val Ser Asp Ile Met Gln Gln Ala Gln Tyr Asp Gln Pro Leu

645 650 655

Glu Lys Ser Thr Lys Leu

660

<210> SEQ ID NO 33

<211> LENGTH: 2363

<212> TYPE: DNA

<213> ORGANISM: Homo Sapien

<220> FEATURE:

<221> NAME/KEY: CDS

<222> LOCATION: (138)...(2126)

<223> OTHER INFORMATION: AKAP-10-5

<220> FEATURE:

<221> NAME/KEY: allele

<222> LOCATION: 2073

<223> OTHER INFORMATION: Single Nucleotide Polymorphism: A to G

<400> SEQUENCE: 33

gcggcttgtt gataatatgg cggctggagc tgcctgggca tcccgaggag gcggtggggc 60

ccactcccgg aagaagggtc ccttttcgcg ctagtgcagc ggcccctctg gacccggaag 120

tccgggccgg ttgctga atg agg gga gcc ggg ccc tcc ccg cgc cag tcc 170

Met Arg Gly Ala Gly Pro Ser Pro Arg Gln Ser

1 5 10

ccc cgc acc ctc cgt ccc gac ccg ggc ccc gcc atg tcc ttc ttc cgg 218

Pro Arg Thr Leu Arg Pro Asp Pro Gly Pro Ala Met Ser Phe Phe Arg

15 20 25

cgg aaa gtg aaa ggc aaa gaa caa gag aag acc tca gat gtg aag tcc 266

Arg Lys Val Lys Gly Lys Glu Gln Glu Lys Thr Ser Asp Val Lys Ser

30 35 40

att aaa gct tca ata tcc gta cat tcc cca caa aaa agc act aaa aat 314

Ile Lys Ala Ser Ile Ser Val His Ser Pro Gln Lys Ser Thr Lys Asn

45 50 55

cat gcc ttg ctg gag gct gca gga cca agt cat gtt gca atc aat gcc 362

His Ala Leu Leu Glu Ala Ala Gly Pro Ser His Val Ala Ile Asn Ala

60 65 70 75

att tct gcc aac atg gac tcc ttt tca agt agc agg aca gcc aca ctt 410

Ile Ser Ala Asn Met Asp Ser Phe Ser Ser Ser Arg Thr Ala Thr Leu

80 85 90

aag aag cag cca agc cac atg gag gct gct cat ttt ggt gac ctg ggc 458

Lys Lys Gln Pro Ser His Met Glu Ala Ala His Phe Gly Asp Leu Gly

95 100 105

aga tct tgt ctg gac tac cag act caa gag acc aaa tca agc ctt tct 506

Arg Ser Cys Leu Asp Tyr Gln Thr Gln Glu Thr Lys Ser Ser Leu Ser

110 115 120

aag acc ctt gaa caa gtc ttg cac gac act att gtc ctc cct tac ttc 554

Lys Thr Leu Glu Gln Val Leu His Asp Thr Ile Val Leu Pro Tyr Phe

125 130 135

att caa ttc atg gaa ctt cgg cga atg gag cat ttg gtg aaa ttt tgg 602

Ile Gln Phe Met Glu Leu Arg Arg Met Glu His Leu Val Lys Phe Trp

140 145 150 155

tta gag gct gaa agt ttt cat tca aca act tgg tcg cga ata aga gca 650

Leu Glu Ala Glu Ser Phe His Ser Thr Thr Trp Ser Arg Ile Arg Ala

160 165 170

cac agt cta aac aca atg aag cag agc tca ctg gct gag cct gtc tct 698

His Ser Leu Asn Thr Met Lys Gln Ser Ser Leu Ala Glu Pro Val Ser

175 180 185

cca tct aaa aag cat gaa act aca gcg tct ttt tta act gat tct ctt 746

Pro Ser Lys Lys His Glu Thr Thr Ala Ser Phe Leu Thr Asp Ser Leu

190 195 200

gat aag aga ttg gag gat tct ggc tca gca cag ttg ttt atg act cat 794

Asp Lys Arg Leu Glu Asp Ser Gly Ser Ala Gln Leu Phe Met Thr His

205 210 215

tca gaa gga att gac ctg aat aat aga act aac agc act cag aat cac 842

Ser Glu Gly Ile Asp Leu Asn Asn Arg Thr Asn Ser Thr Gln Asn His

220 225 230 235

ttg ctg ctt tcc cag gaa tgt gac agt gcc cat tct ctc cgt ctt gaa 890

Leu Leu Leu Ser Gln Glu Cys Asp Ser Ala His Ser Leu Arg Leu Glu

240 245 250

atg gcc aga gca gga act cac caa gtt tcc atg gaa acc caa gaa tct 938

Met Ala Arg Ala Gly Thr His Gln Val Ser Met Glu Thr Gln Glu Ser

255 260 265

tcc tct aca ctt aca gta gcc agt aga aat agt ccc gct tct cca cta 986

Ser Ser Thr Leu Thr Val Ala Ser Arg Asn Ser Pro Ala Ser Pro Leu

270 275 280

aaa gaa ttg tca gga aaa cta atg aaa agt ata gaa caa gat gca gtg 1034

Lys Glu Leu Ser Gly Lys Leu Met Lys Ser Ile Glu Gln Asp Ala Val

285 290 295

aat act ttt acc aaa tat ata tct cca gat gct gct aaa cca ata cca 1082

Asn Thr Phe Thr Lys Tyr Ile Ser Pro Asp Ala Ala Lys Pro Ile Pro

300 305 310 315

att aca gaa gca atg aga aat gac atc ata gca agg att tgt gga gaa 1130

Ile Thr Glu Ala Met Arg Asn Asp Ile Ile Ala Arg Ile Cys Gly Glu

320 325 330

gat gga cag gtg gat ccc aac tgt ttc gtt ttg gca cag tcc ata gtc 1178

Asp Gly Gln Val Asp Pro Asn Cys Phe Val Leu Ala Gln Ser Ile Val

335 340 345

ttt agt gca atg gag caa gag cac ttt agt gag ttt ctg cga agt cac 1226

Phe Ser Ala Met Glu Gln Glu His Phe Ser Glu Phe Leu Arg Ser His

350 355 360

cat ttc tgt aaa tac cag att gaa gtg ctg acc agt gga act gtt tac 1274

His Phe Cys Lys Tyr Gln Ile Glu Val Leu Thr Ser Gly Thr Val Tyr

365 370 375

ctg gct gac att ctc ttc tgt gag tca gcc ctc ttt tat ttc tct gag 1322

Leu Ala Asp Ile Leu Phe Cys Glu Ser Ala Leu Phe Tyr Phe Ser Glu

380 385 390 395

tac atg gaa aaa gag gat gca gtg aat atc tta caa ttc tgg ttg gca 1370

Tyr Met Glu Lys Glu Asp Ala Val Asn Ile Leu Gln Phe Trp Leu Ala

400 405 410

gca gat aac ttc cag tct cag ctt gct gcc aaa aag ggg caa tat gat 1418

Ala Asp Asn Phe Gln Ser Gln Leu Ala Ala Lys Lys Gly Gln Tyr Asp

415 420 425

gga cag gag gca cag aat gat gcc atg att tta tat gac aag tac ttc 1466

Gly Gln Glu Ala Gln Asn Asp Ala Met Ile Leu Tyr Asp Lys Tyr Phe

430 435 440

tcc ctc caa gcc aca cat cct ctt gga ttt gat gat gtt gta cga tta 1514

Ser Leu Gln Ala Thr His Pro Leu Gly Phe Asp Asp Val Val Arg Leu

445 450 455

gaa att gaa tcc aat atc tgc agg gaa ggt ggg cca ctc ccc aac tgt 1562

Glu Ile Glu Ser Asn Ile Cys Arg Glu Gly Gly Pro Leu Pro Asn Cys

460 465 470 475

ttc aca act cca tta cgt cag gcc tgg aca acc atg gag aag gtc ttt 1610

Phe Thr Thr Pro Leu Arg Gln Ala Trp Thr Thr Met Glu Lys Val Phe

480 485 490

ttg cct ggc ttt ctg tcc agc aat ctt tat tat aaa tat ttg aat gat 1658

Leu Pro Gly Phe Leu Ser Ser Asn Leu Tyr Tyr Lys Tyr Leu Asn Asp

495 500 505

ctc atc cat tcg gtt cga gga gat gaa ttt ctg ggc ggg aac gtg tcg 1706

Leu Ile His Ser Val Arg Gly Asp Glu Phe Leu Gly Gly Asn Val Ser

510 515 520

ccg act gct cct ggc tct gtt ggc cct cct gat gag tct cac cca ggg 1754

Pro Thr Ala Pro Gly Ser Val Gly Pro Pro Asp Glu Ser His Pro Gly

525 530 535

agt tct gac agc tct gcg tct cag tcc agt gtg aaa aaa gcc agt att 1802

Ser Ser Asp Ser Ser Ala Ser Gln Ser Ser Val Lys Lys Ala Ser Ile

540 545 550 555

aaa ata ctg aaa aat ttt gat gaa gcg ata att gtg gat gcg gca agt 1850

Lys Ile Leu Lys Asn Phe Asp Glu Ala Ile Ile Val Asp Ala Ala Ser

560 565 570

ctg gat cca gaa tct tta tat caa cgg aca tat gcc ggg aag atg aca 1898

Leu Asp Pro Glu Ser Leu Tyr Gln Arg Thr Tyr Ala Gly Lys Met Thr

575 580 585

ttt gga aga gtg agt gac ttg ggg caa ttc atc cgg gaa tct gag cct 1946

Phe Gly Arg Val Ser Asp Leu Gly Gln Phe Ile Arg Glu Ser Glu Pro

590 595 600

gaa cct gat gta agg aaa tca aaa gga tcc atg ttc tca caa gct atg 1994

Glu Pro Asp Val Arg Lys Ser Lys Gly Ser Met Phe Ser Gln Ala Met

605 610 615

aag aaa tgg gtg caa gga aat act gat gag gcc cag gaa gag cta gct 2042

Lys Lys Trp Val Gln Gly Asn Thr Asp Glu Ala Gln Glu Glu Leu Ala

620 625 630 635

tgg aag att gct aaa atg ata gtc agt gac gtt atg cag cag gct cag 2090

Trp Lys Ile Ala Lys Met Ile Val Ser Asp Val Met Gln Gln Ala Gln

640 645 650

tat gat caa ccg tta gag aaa tct aca aag tta tga ctcaaaactt 2136

Tyr Asp Gln Pro Leu Glu Lys Ser Thr Lys Leu *

655 660

gagataaagg aaatctgctt gtgaaaaata agagaacttt tttcccttgg ttggattctt 2196

caacacagcc aatgaaaaca gcactatatt tctgatctgt cactgttgtt tccagggaga 2256

gaatggggag acaatcctag gacttccacc ctaatgcagt tacctgtagg gcataattgg 2316

atggcacatg atgtttcaca cagtgaggag tctttaaagg ttaccaa 2363

<210> SEQ ID NO 34

<211> LENGTH: 662

<212> TYPE: PRT

<213> ORGANISM: Homo Sapien

<400> SEQUENCE: 34

Met Arg Gly Ala Gly Pro Ser Pro Arg Gln Ser Pro Arg Thr Leu Arg

1 5 10 15

Pro Asp Pro Gly Pro Ala Met Ser Phe Phe Arg Arg Lys Val Lys Gly

20 25 30

Lys Glu Gln Glu Lys Thr Ser Asp Val Lys Ser Ile Lys Ala Ser Ile

35 40 45

Ser Val His Ser Pro Gln Lys Ser Thr Lys Asn His Ala Leu Leu Glu

50 55 60

Ala Ala Gly Pro Ser His Val Ala Ile Asn Ala Ile Ser Ala Asn Met

65 70 75 80

Asp Ser Phe Ser Ser Ser Arg Thr Ala Thr Leu Lys Lys Gln Pro Ser

85 90 95

His Met Glu Ala Ala His Phe Gly Asp Leu Gly Arg Ser Cys Leu Asp

100 105 110

Tyr Gln Thr Gln Glu Thr Lys Ser Ser Leu Ser Lys Thr Leu Glu Gln

115 120 125

Val Leu His Asp Thr Ile Val Leu Pro Tyr Phe Ile Gln Phe Met Glu

130 135 140

Leu Arg Arg Met Glu His Leu Val Lys Phe Trp Leu Glu Ala Glu Ser

145 150 155 160

Phe His Ser Thr Thr Trp Ser Arg Ile Arg Ala His Ser Leu Asn Thr

165 170 175

Met Lys Gln Ser Ser Leu Ala Glu Pro Val Ser Pro Ser Lys Lys His

180 185 190

Glu Thr Thr Ala Ser Phe Leu Thr Asp Ser Leu Asp Lys Arg Leu Glu

195 200 205

Asp Ser Gly Ser Ala Gln Leu Phe Met Thr His Ser Glu Gly Ile Asp

210 215 220

Leu Asn Asn Arg Thr Asn Ser Thr Gln Asn His Leu Leu Leu Ser Gln

225 230 235 240

Glu Cys Asp Ser Ala His Ser Leu Arg Leu Glu Met Ala Arg Ala Gly

245 250 255

Thr His Gln Val Ser Met Glu Thr Gln Glu Ser Ser Ser Thr Leu Thr

260 265 270

Val Ala Ser Arg Asn Ser Pro Ala Ser Pro Leu Lys Glu Leu Ser Gly

275 280 285

Lys Leu Met Lys Ser Ile Glu Gln Asp Ala Val Asn Thr Phe Thr Lys

290 295 300

Tyr Ile Ser Pro Asp Ala Ala Lys Pro Ile Pro Ile Thr Glu Ala Met

305 310 315 320

Arg Asn Asp Ile Ile Ala Arg Ile Cys Gly Glu Asp Gly Gln Val Asp

325 330 335

Pro Asn Cys Phe Val Leu Ala Gln Ser Ile Val Phe Ser Ala Met Glu

340 345 350

Gln Glu His Phe Ser Glu Phe Leu Arg Ser His His Phe Cys Lys Tyr

355 360 365

Gln Ile Glu Val Leu Thr Ser Gly Thr Val Tyr Leu Ala Asp Ile Leu

370 375 380

Phe Cys Glu Ser Ala Leu Phe Tyr Phe Ser Glu Tyr Met Glu Lys Glu

385 390 395 400

Asp Ala Val Asn Ile Leu Gln Phe Trp Leu Ala Ala Asp Asn Phe Gln

405 410 415

Ser Gln Leu Ala Ala Lys Lys Gly Gln Tyr Asp Gly Gln Glu Ala Gln

420 425 430

Asn Asp Ala Met Ile Leu Tyr Asp Lys Tyr Phe Ser Leu Gln Ala Thr

435 440 445

His Pro Leu Gly Phe Asp Asp Val Val Arg Leu Glu Ile Glu Ser Asn

450 455 460

Ile Cys Arg Glu Gly Gly Pro Leu Pro Asn Cys Phe Thr Thr Pro Leu

465 470 475 480

Arg Gln Ala Trp Thr Thr Met Glu Lys Val Phe Leu Pro Gly Phe Leu

485 490 495

Ser Ser Asn Leu Tyr Tyr Lys Tyr Leu Asn Asp Leu Ile His Ser Val

500 505 510

Arg Gly Asp Glu Phe Leu Gly Gly Asn Val Ser Pro Thr Ala Pro Gly

515 520 525

Ser Val Gly Pro Pro Asp Glu Ser His Pro Gly Ser Ser Asp Ser Ser

530 535 540

Ala Ser Gln Ser Ser Val Lys Lys Ala Ser Ile Lys Ile Leu Lys Asn

545 550 555 560

Phe Asp Glu Ala Ile Ile Val Asp Ala Ala Ser Leu Asp Pro Glu Ser

565 570 575

Leu Tyr Gln Arg Thr Tyr Ala Gly Lys Met Thr Phe Gly Arg Val Ser

580 585 590

Asp Leu Gly Gln Phe Ile Arg Glu Ser Glu Pro Glu Pro Asp Val Arg

595 600 605

Lys Ser Lys Gly Ser Met Phe Ser Gln Ala Met Lys Lys Trp Val Gln

610 615 620

Gly Asn Thr Asp Glu Ala Gln Glu Glu Leu Ala Trp Lys Ile Ala Lys

625 630 635 640

Met Ile Val Ser Asp Val Met Gln Gln Ala Gln Tyr Asp Gln Pro Leu

645 650 655

Glu Lys Ser Thr Lys Leu

660

<210> SEQ ID NO 35

<211> LENGTH: 162025

<212> TYPE: DNA

<213> ORGANISM: Homo Sapien

<300> PUBLICATION INFORMATION:

<308> DATABASE ACCESSION NUMBER: GenBank AC005730

<309> DATABASE ENTRY DATE: 1998-10-22

<400> SEQUENCE: 35

gaattcctat ttcaaaagaa acaaatgggc caagtatggt ggctcatacc tgtaatccca 60

gcactttggg aggccgaggt gagtgggtca cttgaggtca ggagttccag gccagtctgg 120

ccaacatggt gaaacactgt ctctactaaa aatacaaaaa ttagccgggc gtggtggcgg 180

gcacctgtaa tcccagctac tcaggaggct gaggcaggag aattgcttga acctgggaga 240

tggaggttgc agtgagccga gatcgcgcca ctgctctcca gcctgggtgg cagagtgaga 300

ctctgtctca aaaagaaaca aagaaataaa tgaaacaatt ttgttcacat atatttcaca 360

aatttgaaat gttaaaggta ttatggtcac tgatatcctg tttcattctt tatataatca 420

ttaagtttga aatgtatact tgcactacta acacagtagt taatcttagt cctacaagtt 480

actgctttta cacaatatat tttcgtaata tgtatgcact ggtgtttatg tacgtgttta 540

tgtttatatc tgttaaaatt agcagtttcc atctttttct attttgtacc atcacatcag 600

ttcagaagga ttgacagagc aaaatgattt gatgaagtat aaaagtcaca tggtgagtgg 660

cataaataca actctgaaca attaggaggc tcactattga ctggaactaa actgcaagcc 720

agaaagacac atatcctata tgtcaagaga tgtaccaccc aggcagttaa agaagggaag 780

tacacataga aagcacaatg gtgaataatt aaaaaattgg aatttatcag acactggatt 840

catttgctcc taaagtcaga gtcctctatt gtttttttgt ttttgtgggt ttctttttaa 900

atttttttat tttttgtaga gtcggagtct cactgtgtta cccgggctgg tctagaactc 960

ctggcctcaa acaaacctcc tgcctcagct tcccaaagca ttgggattac agacatgagc 1020

cactgagccc agcccagacg ctttagcatt tatgaagctt ctgaaatagt tgtagaaacc 1080

gcataagctt tccatgtcac tttcaaagtt tgatggtctc tttagtaaac caaccaagtt 1140

attcctcaag ggcaaaataa catttctcag tgcaaaactg atgcacttca ttaccaaaag 1200

gaaaagacca caactataga ggcgtcattg aaagctgcac tcttcagagg ccaaaaaaaa 1260

aggtacaaac acatactaat ggaacattct ttagaagagc cccaaagtta atgataaaca 1320

ttttcatcaa agagaaaaga gaacaaggtg ttagcaaatt cctctatcaa ataacactaa 1380

acatcaagga acatcaatgg catgccatgt ggaagaggaa gtgctagctc atgtacaaac 1440

cagtagataa tttcaacttg ctgccgaatg aaacctcttt gcaaggtatg aatcagcact 1500

tctcatgttt gttttgcttt gttttgtttt gtttttagag acaggccctt gctctgtcac 1560

acaggctgga gtgcagtggc acgatcagag ctcactgcaa cctgaaactc ctgggctcaa 1620

gggatcctcc tgccttagcc tcccaagtag ctgggactac aggcccacca tgcccagcta 1680

attttttaaa ttttctatag agatgggatc tcactagcac ctttcatgtt tgatgttcat 1740

atacaacgac caaggtacaa tgtggaaaag ggtctcaggg atctaaagtg aaggaggacc 1800

agaaagaaaa ggggttgcta catagagtag aagaagttgc acttcatgcc agtctacaac 1860

actgctgttt tcctcagagc agagttgatg atctaaatca ggggtcccca acccccagtt 1920

catagcctgt taggaaccgg gccacacagc aggaggtgag caataggcaa gcgagcatta 1980

ccacctgggc ttcacctccc gtcagatcag tgatgtcatt agattctcat aggaccatga 2040

accctattgt gaactgagca tgcaagggat gtaggttttc cgctctttat gagactctaa 2100

tgccggaaga tctgtcactg tcttccatca ccctgagatg ggaacatcta gttgcaggaa 2160

aacaacctca gggctcccat tgattctata ttacagtgag ttgtatcatt atttcattct 2220

atattacaat gtaataataa tagaaataaa ggcacaatag gccaggcgtg gtggctcaca 2280

cctgtaatcc cagcacttcg ggaggccaag gcaggcggat cacgaggtca ggagatcgag 2340

accatcctgg ctaaaacggt gaaaccccgt ctactaaaaa ttcaaaaaaa aattagccgg 2400

gtgtggtggt gggcacctgt agtcccagct actcgagagg ctgaggcagg agaatggtgt 2460

gaacctggga ggcagagctt gaggtaagcc gagatcacgc cactgcactc cagcctgggc 2520

gacagagcga tactctgtct caaaaaaaaa aaaaaaaaaa aaagaaataa agtgaacaat 2580

aaatgtaatg tggctgaatc attccaaaac aatcccccca ccccagttca cggaaaaatt 2640

ctcccacaaa accagtccct ggtgccaaaa aggttgggga ccgctaatct aaataatcta 2700

atcttcattc aatgctaaaa aatgaataaa ctttttttta aatacacggt ctcactttgt 2760

tgcccaggct ggagtacggt ggcatgatca cagctcactg tagcctcaat cacccaggcc 2820

ccagcgatcc tcccacctaa acttcctgag tagctgggac tacaggcacg caccaccatg 2880

cccagctaat ttttaaattt tttatagaga tgggggtctc accatgttgc ccagactggt 2940

ctcaaaccct gggctcaagt gatcctccct caaactcctg gactcaagtg atcctccttc 3000

cttggcctcc caaagtgctg ggattacaag catgagccac tgtacccagc tggataaaca 3060

ttttaagtcg cactacagtc atggacaatc aggcttttca acatgcagta tggacagtga 3120

gtcccagggt ctgcttttcc atactgaaat acatgtgata ctaaggagaa aggtgctcgc 3180

aaggatattt aaaatgaaga atatttaaaa tgaggaaaaa actgtttctt catgactttg 3240

ataaggctga taaagaccat ttctgtgatc tcaggtgatt cactcaagta gtatatttca 3300

gtaatcatta tctggaacag cctgaatctt aaccaaaata ccatgatttt ttaatgctgt 3360

tatgatacct tgatgatatg accaaactgc aatgtaggca gctaaatctc cacgagtttg 3420

acttccccga gagttgacag ttttcttcac aaattaaaga aatatatttt ttgatacatg 3480

attggcatat ttaaaaacta cactgaaatg ctgcaaaatg atataaagaa acattttcca 3540

gaatcaaatg caatcaaaga gtggattagg aatctactca ccattatcaa ctaaatagaa 3600

acacttggac tgggtgtggt ggctcacatc tgtaatctca gcactttggg aggccaaggc 3660

aggtggattg cttgaggcca ggagctcaag accagcctga gcaacatagc aaaactctgt 3720

ctctacaaaa aaaaaaaaaa attaaccagg catggtggca gatgcttgta atcccagcta 3780

ctctggaagc tgaagtagga ggactgcttg agcccaggag atcaagactg cagtgagccg 3840

tggtcatgct gcgccacagc ctgagtgaca gagagagacc ctgtctcaaa aacaaaaaca 3900

aacaaaaaac acttaacctt cctgtttttt gctgttgttg ttgttgtttg tttgttttga 3960

gatggagtct cactctgttg cccaggctgg agtgcagtgg cgtgatcttg gctcactgca 4020

agctctgcct cccgggttca cgccattctc ctgcctcagc ctcccgagta gctgggacta 4080

taggcgcccg ccaccacgcc cggctacttt tttgcatttt tagtagagat ggggtttcac 4140

cgtgttagcc aggatggtct tgatctcctg acctcgtgat ccacctgcct cggcctccca 4200

aagtgctggg attacaggca tgagccaccg cacccggcca acctttctgt tttttagttt 4260

gatatgcttg ttaactcagc agctgaaaga atgctgaaag tggccttcag taaaaaaatt 4320

tcactagaat ctctacatcc atatttaatc tgaatgcata tccagattga tcagttagag 4380

caaaaacact catcatcatt cctgatgacc tctaattctg gtttcggctt tctatttcaa 4440

tggaaacaga ataaggaaag aaatggaagg gctctggaaa tttgtcctgg gctatagata 4500

ctatcaaaga tcaccaacaa taagatctct cctataaata taaaacaagt ataattaatt 4560

ttttaattat ttttttctct tcagaggatt ttatttcaag ataaaacata acttctaccc 4620

atactattga ttccaaaggt tagaaaaagt gtttttcctc atcttatcct tcaaagaggt 4680

cacagcaatg caaacatcta taaaatgcct ctgcataatt gtcagaagct atagtccaga 4740

aatcattgaa aatgcttttc cattttaagc ttaggtgagg tgtcttagga aacctctatg 4800

acaacttact ctatttattg ggaggtaaac tcccagactc tcccagggtc tcctgtattg 4860

atctcatttt ttaggcttcc taatcccttg aagcacaatc gaaaaagccc tggatctctt 4920

ttctgcacat atcatcgcgg aattcattcg gcttccagca agctgacact ccatgataca 4980

agcggcctcg cccttctccg gacgccagtc cttgctgcgg ttagctagga tgaggggttt 5040

gctgggcttc agtgcaggct tctgcgggtt cccaagccgc accaggtggc ctcacaggct 5100

ggatgtcacc attgcacact gagctcctgg caggctgtac caatttttta attatttaat 5160

atttattttt aaaattatgg tgaatatttt ggtattctgc tctaaaatag gcccataaat 5220

gcacagcaga tatctcttgg aacccacagc tttccactgg aagaactaag tatttttctt 5280

ttaaagatgc tactaagtct ctgaaaagtc cagatcctct acctctttcc atcccaaact 5340

aagacttgga atttatgaga gatctagcta acagaaatcc cagacacatc attggttctt 5400

cccagagtgc agtcctccta aagaggctca gccctaagca ggcccctgca ccaggagggt 5460

gggtctgaga cccacatagc acttcccaag gtgcatgctc cagagaggca ctgaaacagc 5520

tgagcacaag cctgcaagcc tggagaactc tcacagtcag aacggagggg gcccagtggg 5580

actaacataa agagaaaagg gaacacagag aaatggatgg caccaacaac cagcaaagcc 5640

ttcatggcca atgaaagcat cagtgacggg gccagaaccc tcatccccaa agactcttca 5700

ctgcctttag tgaaaaacaa tggctagaga gtgaagttat gatcatgtat agagaggtaa 5760

agttacattt ttatattctg actctgctaa tgtgaaattc cctatctgct agactaaaag 5820

tttcagacac cctgttcaaa tatcccatta gttgctagag acttaaaatg aacagaacgc 5880

acattgtcag gatgactatt accaaaaaat caaaagacag caagtattgg tgaggatgta 5940

gagaaactgg aacttttgtg cactgtttat gagaatgtaa aatggagcag ctgctgtgga 6000

aaagagtatg caggttcctc aaagagtaaa accaagatgt ggaaacaact aaatgcccat 6060

cagtggatga aggggtagac aatatgtggt atatacatac catggagtac tattcagcct 6120

ctaaaaaaaa aaaaggaaat tctataacat gcaacagcat ggatgaatct tgaggacatt 6180

ttgctaatga aataaggcag tcatagaaag acaaatactg cacgactcca cttatatgag 6240

ataccaaaaa tagacaaatt catagaatca aagagtacaa tggaggttac ctggagctgc 6300

agggcgggaa acgaggagtt actaatcaac gaacataacg ttgcagttaa gtaagatgaa 6360

taagctctca agatcagctg tacaacactg tacctagagt caacaataat gtattgtaca 6420

cttaaaaatt tgttaagggt agattaacaa atgtagtaga tccacaaatg tggttaagtg 6480

ttcttaccac agtaaaataa aaaaagaata tcaagcccag gagttcgaga ctagcctggg 6540

taacatggtg aaaccctgtc tctacagaaa atacaaaaat tagccagctg tggaggtgca 6600

ctcctaggga ggctgaggtg ggaggcttgc ttgagcccag gaggtcaagg ctgcagtgag 6660

ccatgattgc accactgtac tccagcccag atgacagagc aagacaccac cccccccaaa 6720

aaaagaaaaa gaatatcaaa cattttaaaa gatcagatac gcaagaacaa caacaaaaaa 6780

gagatgaaca gagcatcgac cctcatctag tgggattctt ggtctaactg aaaaacagac 6840

attgagagac aaacaatgac agtgatgtga tcacagcaat tacacaggta tcccctgggg 6900

actgcagaag aaaggaggaa tgcctaactt tcagaaaata gagaaagcgt caaacagttg 6960

gtgaaagcct tccaaaacta gagagaactg cacacaccaa atcacagaaa gaagaaaagc 7020

cgtgggagat tctgggaccc accggctatt tttgatggct gaacaccctg ctgcaggaga 7080

gacaggagct ggaaagcatg gtgggatgaa acctcaaaca gctttgcctg cattgcttaa 7140

gatgactggg cttgattaac tctagtcaat ggggacaatt caatcaaaga agaaagatgc 7200

tcaaattcac attttagaat gattttttat ggcagtatgg ggaatagatt aaaagagagt 7260

gaagctggag gcaagaaact tgttaagagg caactgaaac agtctagatg ataaataata 7320

aactgacaga gtgactagaa aaatcagaac aggctgaatc aacagatacc tagatgaaaa 7380

taacaggact tgatcaccag ttgtatcttg gagaggaagg agttgtttcc ttgctttccc 7440

tacgactggg aatacggaag gtttgccgtg tgtattggtt atatactggt gtgtagccaa 7500

tcactgacaa ccatttagca gcttaaaaca caaaggctta tctcccagtt tctgtgggcc 7560

aggaatctaa gataggctta gctggctggt tctggctcag agtttctcaa gaggttgcaa 7620

tcaagatgtc agctggggtt gcatcatctg aaggctcaac tggggccgga gggtccactt 7680

ccaaggagtt cactcacctg cctgacaagg cagtgctggt tgttggcagg agatctcaat 7740

tcattgccaa gtgagcctct ctatagcatt gctggaacat cctccccatc tggcagttgg 7800

cttctctcag catgagtgat ctgagagaga gagcaaggag gaagccacag tgttcttcct 7860

actcctactc ctaacactat ggacctactc ctaacactct cacttctgcc ttattccatt 7920

agttagaaag ggaactaagc tccacctctt gaaataagaa gtgtcaaaga atttgtggat 7980

atatttaaaa atcatcacac tgtggaagtg gatagggggt tcaattaatg ctgaacttga 8040

aatgcctgag acattcaaat gtccaacagg caatgaacat acccatagat ggtcatgact 8100

ttagcaagaa tagaggaaga tcacagaatt aaggaggaat tgaaaggtaa aagaagtgga 8160

gtcagattcc ccctgaaaag tgagccatga aaggaacttt aactattgag ttagaggtca 8220

gagtaggaaa tttcggtgga attctttttt aaagaaagga accatataag catgttttga 8280

ggtagaggga gaataaatca gtagacaggg agaggtaaaa aacataaatg ataggggata 8340

gttgacaaag gtcttggcag aatcccttac ccattgactt ggggccaaga gagggacact 8400

tctttgtttg agggataagg aaaataagaa agaatgggtg ctatttagtg tggtcctgtc 8460

tctagggcaa acgcataggt aacaaactgt gtgtgttagg aatatagatg tgacctcaca 8520

ttgagattct cacctcaaat ccattttgtt gttacctgta ccttcctacc ttctcttttt 8580

gctacatgca gactgctgtt ttgtcttcct ggcctgttcc aggtttcagc attctggcat 8640

atctgctacc ctgttcccaa acctctctag agtccatgct ccttccttgg atagtgtttg 8700

attgggccac gtatctaaga agtgatgcct tcagttaggc ctgagaacct cctctatgga 8760

aatctccatc agtgaccctg acagacttgg tatcttggag atgtcactgc tcccagcctg 8820

tggtctagga gaatctcagc ctgggcctct agtagtatgg ataaggcgtt aaggtatctt 8880

tgaaccagag tctgtcatat tcctcaatgt gggacagata aaacagtggt agtgctggtg 8940

tttctgagct agaactctgg tttttggtct agattctttg atgtatgacc tttcagaggt 9000

attaaaattt gttctaatac aatgttcaat acaaatgtag ttccttttct gttaggacct 9060

caacaaaaca tgaccaactg tagatgaaca ttaaactatg acaattcatg gaaatgaata 9120

cagtaatacc tgcggttccc ccattttagc agtcactatg gtgacatttg gcacaaatgg 9180

ctatttaagg gtgcttttgt taaaacctac catcttacta ggcacatgat attgaaacta 9240

atgaaataat ggagaaactt cttaaaaact tttaatgaat aaagtgatga agtgataata 9300

ttttagctgc tatttataaa gtgactatta caggtcaaac attcttctag ggtttttttg 9360

ttgaagttgt cacatttaat ccttaataac ccactatgag tcaggtattc ttctctcccc 9420

tttggacagt tggggaaatg ggggtcagag aggttaggta atttgctcag ggccacacaa 9480

cctgcatgta gaaaatctga gatttgtaca ggaacgtatc aaactctgaa gtccatgctt 9540

ctattttccc atgctgcctt tctaataaaa ggtaactaat gctactggat gctgccccca 9600

aagtgagtca ctttcacccc accctacttg attttctcca taaaactaat cacatcctga 9660

caacttattt attgctgatc tcccccacta gattataaac tcaataaaag caagatcctt 9720

gtctgctgaa tatcagtacc taaaacgctg tctagcacag agcaagtaat taatatttgt 9780

tgaatgaaca aataaaggaa aaaaattcaa aggaagaaaa agccctaaaa cagatgttta 9840

cctaaacata cattttaaaa gaaagcatat aacaaattca ggacagaatt taaatttgat 9900

tttttaaaga aataaccaag tgctagctgg gcacagtggc tcacacctgt aatcctagca 9960

ctctgggagg ccgaggcagg cagatcactt gaggtcaaga gttcaagacc agcctggcca 10020

acatggtgaa acctgtctct actaaaaata cagaaattat ccaggcatgg tggcaggtcc 10080

ctgtaacccc agctactcag gaggctgagt caggagaatt gcttgaaccc aggaggcaga 10140

ggttgcagtg ggccaagatt gcaccactgc actccagcct gagtaacaaa gcaagactct 10200

gtctgaagga gaaggaaaga aagaaggaaa gaaggaaaga aggaaagaag gaaagaagga 10260

aagaaagaaa gaaagaaaga aagaaagaaa gaaagaaaga aagaaagaaa gaaagaaaga 10320

aagaaagaaa aagaaagaaa gaaagaaaga accaagtgct tatttgggac ctactatgct 10380

atgtttttcc atgcacgcta ttttcagtaa agcagttagc aaacttgcaa gatcataaca 10440

acaaatatat gcttctataa ctctaaaatt gtgctttaag aagttcctct ttaccagctc 10500

atgtatgcat tagttttcta agagttacta gtaacttttt ccctggagaa tatccacagc 10560

cagtttattt aaccaaagga ggatgcttac taacatgaag ttatcaaatg tgagcctaag 10620

ttgggccagt tcatgttaat atactccaga acaaaaacca tcctactgtc ctctgacaat 10680

tttacctgaa aattcatttt ccacattacc aaggagccag ggtaggagaa tatagaaaga 10740

ccacccaaga atccttactt ctttcagcaa aatcaattca aagtaggtaa ctaaacacat 10800

gccctaacaa tgaatagcag attgtgctca gaagaatgat ctacaacatc ttactgtgaa 10860

ggaactactg aaatattcca ataagacttc tctccaaaat gattttattg aatttgcatt 10920

ttaaaaaata ttttaagcct aaattttaaa aggtttgata ttggtacatg aatagacaaa 10980

cagacatgga ctagaccaag aattaggttc aaacatatac aggaatttaa tatacgataa 11040

atctagtatt ccaaaggaac caacaaatgg tgttcagaca gcaggatagg catcaggaaa 11100

aacacagttg ggcaccctac cttactccta acaccaggag taactgaagg agcaccaaat 11160

atttatttat tttaattata gttttaagtt ctagggtacg tgtgcacaac atgcaggttt 11220

attacatagg tatacatgtg ccatgttggt gaggagcacc aaatatttaa aagaaaaaaa 11280

ttggccaggg gcggtggctc acacctgtaa tcccagcact ttgggaggcc aaggtgggca 11340

gatcacctga ggtcgggagt tcgagaccag cctgagcaac atggagaaac cccatctcta 11400

ctaaaaatac aaaattagcc aggcatggtg gcacatgcct gtaatcccag ctacttggga 11460

ggctgaggca ggagaatagc tttaatctgg gaggcacagg ttgcggtgag ctgagatatt 11520

gcactccagc ctgggcaaca agagcaaaac ttcaactcaa aaaaattaat aaataaataa 11580

aaataaagaa agaaaagaaa aaaatgaaaa tagtataatt agcagaagaa aacaccgtag 11640

aatcctcgga ctcttaggat ggggaatgcc tataatataa aaaccctgaa gttataaaag 11700

agaaaatcac ctacatacaa accaaatctt tctacatgcc taaaacatag cacaaacaca 11760

gctaaataat catagctgaa tgaactggga aaacaaaact tgactcatat ccagacagag 11820

ttaattttcc tacacataaa gagtacctat ataaacccaa caaaaaaacc accactaacc 11880

caaaataaaa atgtgacagg taatgaacag gtagttcaca gagaatacaa atggctcttc 11940

ggcacataag atgctcagac tgacttttac ttatttattt tttgagagac agggtctcac 12000

gatgttgccc aggttaggct caaactcctg ggctcaaatg atagtaccag gactacaggt 12060

gtgccccacc gcacctggct cctcaaccac ctgtattaac aggaaatgca aaataaaact 12120

ttcaaatcta ttttacctat tagaatggca aaaatttgaa aaacttcaaa catcatcatg 12180

ttggtgagaa tgtgaggaga ctggcactct cattttttgc tgatagcata tatatactga 12240

tggcttctat ggaaagcaat ctggcagcgt ctatcaaatg tacaagtgca tatatccttt 12300

gacaaagcaa ttccactcta ggaatgtgtt ctatatggtt gtgcttcctg gggctgggaa 12360

ctgggagcta agggacaggg gcagaagata atcttctttt ccctccttcc ccgttaaaca 12420

tgttgaattt tatatactgt aatatattat ttttcacaaa agataatttt taagcgatat 12480

gtctgggaat tttttttttt cttttctgag acagggtctc actctgtcat ccaggctgga 12540

atgccatggt atgatctcag ctgactgcag cctcgacctc ctgggttcaa gcaatcctcc 12600

cacctcagcc tcctgagtag ctgggactac aggcacgtgc catcatgcta atttttgtat 12660

atacagggtc tcactatgtt gcccaggcta atgtcaaact cctaggctca agcaatccac 12720

ccacctcagg ctccaaagtg ctgggattac aggcgtgagc caccgcgcct ggccctggga 12780

attcttacaa aagaaaaaat atctactctc cccttctatt aaagtcaaaa cagagaagga 12840

aattcaacct ataatgaaag tagagaaggg cctcaaccct gagcaacaaa cacaaaggct 12900

atttctgaga caggaatttg ctgaacaaaa tcgagggaag atgacaagaa tcaagactca 12960

cttctcggct gggcgcagtg gctcacacct gtaatcccag cactttggga ggccgaggcg 13020

gacagatcac gaggtcagga gattgagacc atactggcta acacagtgaa acccagtctc 13080

tactaaaaat acaaaaaatt agccgggcgt ggtggcaggt gcctgtagtc ccagctactt 13140

gggaagctga ggcaggagaa tggcgtgaac ccaggaagcg gagcttgcag tgagccgaga 13200

tcacgccact gcactccagc ctgggtgaca gagcaagact ctgtctcaaa aaaaaaaaaa 13260

aagactcatt tctctagatc ttgagccgta ttcaaattta tctcagctta gtgagaggtt 13320

aaagcaagga atatccttcc ctgtgggccc tgctccttac tgaaggaagg taacggatga 13380

gtcaaggaca ccaatggaga aaagcactaa caccattatc tgatgaacat tacgtgaaga 13440

agggtaagaa gtgaagtgga attgctgaag aagtcagtga aagcggacat tcatttgggg 13500

aaatggaata taggaaatcc ataaaagtga ttaaaaagat gttagaggct gaggcggggg 13560

gaccacaggg tcaggagatc gagaccatcc tggctaacac ggtgaaaccc catctctact 13620

aaaaatacaa aaaattagcc aggcgtggtg gcaggcacct gtagtcccaa ctactcggga 13680

gactgaggca ggagaatggc atgaacctgg gagacggagc ttgcagtgag ccgagatcac 13740

gccactgcac tccagcctgg gtgacagagt gagactccat ctcaaaaaaa aaagttagat 13800

acgagagata aagatccaac agacacacaa ctgctaattc tgaacagaac aaaacaaatg 13860

gcacaggaaa agaaaattta agatataaca ccggaaaact ttcctgaaat tgagtaactg 13920

aatctatagc ttgaaagggt ttagcatatg ccaagaaaaa tcagtagagt ccaaccagca 13980

caagacacat ctagcaaggc tggtgattct accaacacag agaaagaagt gggtgaccca 14040

taatgcggaa aaaggcagac catctgcagt cttctccaga acactggagt ctgaagacaa 14100

aagaatgctg cctactgagc cagaagggag agaaagtgac ccaacacatc tttaccaagt 14160

tagaatgtca cgcattattt aaaggctgca aaagccatga aagacatgaa agaacacaag 14220

catttacaac atgaaagaac acaagcattc tcatactcaa gaatccttaa gaaaaatgta 14280

gtcctaatcc agcccactga aagttaaatg tacttaatgt gctcattaat gggaacttca 14340

tagcttcaaa tcagtctggt cccatctacc aacatctctc gcccggcttt cctgcaatag 14400

tcagcacctt tccctcctcc cagtcttgtc ccctggagtc tgctctcagc atagcagagt 14460

gaccacatca acacccaagt cagagccctc cagtgcgcac tggtctacaa agcccttccc 14520

accccccacc ccacgtgccc tccggatcct tgtgacgtgt ctcctgcata ccctagcagc 14580

cctggcctcc tcactgcccc tcctgtacat caggaaggcg actccttgag tcttggctct 14640

ggccgcctcc tccacctgca gtgagttaac tcccttacct actctaggtc attgctcaaa 14700

tgtcagcatc tcaatggggc cctccctgac taccctattt aaattctaca tactcccctt 14760

gaccccatgg acctcactca ccctattcca cttttattct tacaatttag cacttgttct 14820

cttctaacgt attctaagac ttactcattt attacattgt ttgccacccc ctctagtaca 14880

taaactccag aggggcaggg atttctgtct atttattcat ttctttatcc ctaggacata 14940

gaacagggca tagttcagag tattcaatgt tatcaatgaa tgaactagca gtagtaccag 15000

ttccagttag gcacagaatt aaatctaaat agaattaaat ctcatggtct gggttaacta 15060

tggatagaaa attagatata attttaagaa gcctagaaag aaaaaattaa taatgtaaaa 15120

ataatattaa tttgataata ataacaaaaa ctctgccagg cactgtggct caaatctgca 15180

atcccagcta ctcaggaggc tgaggtggaa ggatcacttg agaccagagt tcaagactca 15240

gcctaggcaa cacggcaaga aactgtctct aaaaaaatta aaacttaaat ttttaaaaaa 15300

gaattctcaa agcgtcacaa aaactggaga ttaaggtaca ggaagtgtga agtaatatta 15360

ctatgctaat ggtttttttt ttttttagaa aggtataacc aaaagatttc tttctcaagt 15420

cgataaactg agaaagataa gcatatcttc caattaacag agggggagga aaagccagat 15480

acaacaaaat aagatataaa ttagtttcca gttgaaaaca agagtaggag ttattttgca 15540

tcacctcacc tgtgacctcc cccagcccaa aaaacactac tgataaacag ggtagaaaag 15600

catcatctca gataaagcag gaaaaactgc cacagtctca aaccacaaac tataagcaca 15660

cacctggcca accctgccaa gtctgggctc agtaggagga acgtgctgag agctaggatg 15720

taccaactta gacattctgt gggatacaga tgtccctgga agggtcacac catctcaaag 15780

gcacctgtaa tgcccactga ttacagccac catatgtgag agagaaactc agggcactta 15840

gagagtataa caagaacctt atgtcatctg agatgaggaa tcctcagccc tgcaaattaa 15900

ccaactcttt agaacaactg gcaaaacata aatatccaca acttttgttt cagtaattcc 15960

actcttagat atcaatccaa agtacatgag acagcagata cacacacaaa atggtattta 16020

ctgcagcatt gtttataata gcaaaaaaca agaaataatc catatgtctc aataggatac 16080

tgggtacatg agggtatgta cccatcattc aaccatcaaa aagagtgata tggatgtcca 16140

cagatggaca taaaaagctg tgtgttacgt gaaaacaaac tcaagcagca gcaggatggg 16200

cttatgatag tcagtatgag ctaatttctg gaaaaaaaaa tctagtgtgt gcacagaaaa 16260

catctgaaag aacagaaaca aaactatcag cagaatattg agatgtttta ctaagttgta 16320

tatctatact gcttgtaatt tttaccccaa gcaagaatta ctttttggaa aaagaaaatt 16380

caggaaataa agcatttctt taaacttcat gtttaaacaa atggtgatgg aataaaagag 16440

ttcttattca tcataaacac acacagcaca catgcacgca tgtgcgtgag cacacccttt 16500

acttgataaa taccatgttg aatattttag tctttccttt taggttctat cccttcactc 16560

aaaatgcggt tataaataaa tgtacttttc atgtgccttc tgcctaaacc cactttaata 16620

taactttaca gtcccattat cattatagtc tcaaagctag actcagcctg aaactaccct 16680

ttcatttgga acccttatta aaatgccaca tacagctcct tcaaataaaa acaaacccta 16740

ggacctgaca ctaggcttcc tttgttgcta ctcataatgg ccaagttctg tgcttataat 16800

acatcttctt tcattttatt gctacatatc caagggtttt atatgttttt cttattatat 16860

cttaattcaa aacaccatca cgctcttttc cagatgaaaa taaggaaaag aaattgagca 16920

actgactgac ttaaaggtca taaaactata tagtagcaga gtcagcaaaa gaagaaacac 16980

acatctccca agtagaggct gaaaaccagt accattcacc tccagggtga gctatataca 17040

gattacaaag tcaccttctc taaatgttca aactgaatcc catacccata ctttaccact 17100

acctcgtaag aacagcctca gatcttgtta tagccttttt tttagcatgc tgaagccaat 17160

aaaatgcttc ccattcagca agagaaacaa gttctgaaac actgaataat ctgcccaggg 17220

cctatgaaca tttccactgt gagaaatgtt ctccactgtg tggagaagat ccttactctt 17280

ctccacacag gcagaacatt agaaaaattc ttggattcta tgatgcacag cttaggagtc 17340

tgtttagcac aatttaagtc caaatagtta ttaaatcctc ctctgttcca gaaacagtgc 17400

taaatactgt gaatataaaa attgaaaaga tactctcctg gctcccaaga aagtcagcca 17460

gatagaggag acacaggcac acaaatcact gtcacatgaa gctctacctc cctaacttca 17520

aacgagggcc taagtcacca agaatacagt agcagttgtg actacgagta actactataa 17580

ttcaatactt tatcttccct tagaaaactc ttctcccttg gaaatttatt tgcatttcta 17640

aataccattc cttactaaaa ggaagcaggg ctccttgggg aaatagctga ttctaggtgt 17700

ggactatgaa atgaaaatgg tgagtctggg acatcccatg ttgcccagaa atcaaggaac 17760

tgcccaaaga ttaacagagt catgttaaat ggacctaaga gtgaaccaga aggagctcac 17820

tttgccccgc gtggaacaat ttcaagaaaa acatgacagt aatgaattat aaaacatgaa 17880

ttaaaataca tattggtact aaaaagagaa caaaaggatg tggctttgga taaagctctt 17940

cttcatggaa gaataccagc taataaatgt aaaggaaatg agagaattag aaaaattatc 18000

attttgtaaa ccttaatata ttcacctaga catgctaaaa ccactgagta aaaggctgct 18060

tgggaagagg atgctcacat gatctcagag tttcacacca cagataattt attagataca 18120

ggaaggaaga tgtgatcaag cttcctgtga cccccagcca ggccccacaa cactatgtgc 18180

ctccttgtga tgtgggagct acacagcatc gcccacacag cttctcgcca aaactgtttg 18240

aagctaatca caagggaaga actggacagc ttctgaccat gagacgctcc accagacaac 18300

ttgcttggcc tctccaaaga aacttgcttg gcctctccaa agaaaactca gtttcattta 18360

aaaacaaaac taattattta aaaacaaacg aaaagcaagt tgtggacttg agctccaggg 18420

acagagcaga catacttttc cctgttcttc ccagtaagtg gtaataaaaa ccctcaacac 18480

tagatataaa acaaatataa gaaggttctg gaaggggaag aggaggcaga ctatccaggt 18540

gccttgaggc ccacagaaca acccagtgat gggttcactg ggtcttcttt ttgcttcatt 18600

atctcagact tggagctgaa gcagcaggca acttcaaaac accaaggggc acagattgaa 18660

aagccccaag aaaagcctgc cctctctagc caaaggacca ggaaggagac agtctaatga 18720

gatggaacac atttagacag taactgccca tttaccagca ataactgagc agggagccta 18780

gacttccagt cttgtgagga cgtaccaagg tacccaacac ccccaccaag gctgagtaag 18840

gactgcgact tttatccctg catggcagta gtaaggagcc catccctcac ccgccagcag 18900

tgtcagggga acctggactt ccactcccac ccaggagtga tgaggccctc cctgctgggg 18960

tcatgtcaga ggaggcctag tggagattca gtgacttaac cttttcccag agataatgag 19020

gccacctttc ctccctcttc ccccatggtg acagtgaaag cactgtggca agcagtaggc 19080

actcctaccc ctcctagcca gggaggtatc agggaggcca agtagggaac cagaataccc 19140

acaaccaccc agcagcaaca ggggtccccc accccattgg gtgtcaatgg aagcagagcg 19200

gaaagcctgg atatttaccc ccatctagaa gtaacaagct gatgtccccc ttcttctact 19260

acaatggtgt tcaaaacagg tttaaataag gtctagagtc tgataacgta atacccaaat 19320

cgttgaagtt ttcattgagg atcatttata ccaagagtca ggaagatccc aaactgaaag 19380

agagaaaaga caattgacag acactagcac taagagagca cagatattag aactacctga 19440

aaggatgtta aagcacatat cataagcctc aacaggctgg gcgcggtggc tcacgcctgt 19500

aaccccagca ctttgggagg ccgaggcagg tggatcacaa gatcaggaga tcgagaccat 19560

cctggctaac acggtgaaac cccgtctcta ctaaaaatac aaaaaaaaat agcaaggcat 19620

ggtggtgggc acctgtagtc ccagctactc gggagcctga ggcaggagaa tggcatgaac 19680

ctgggaagag gagcagtgag ccgagatcgc accaccgcac tccagcctgg gcaacagagc 19740

aagacttcgt cccaaaaaaa aaaaaaaaaa aaaaaaaagc ctcaacaaac aactacaaac 19800

gtgcttgaaa caaatgaaaa aaaaatcttg gcaaagaaat aaaagatata tattttggcc 19860

aggtgcagtg gctcacagcc tgtaatccct gcactttggg aggctgaggc aggcggatca 19920

cctgaggtca ggagtttgag accagcctga ccaacatgga gaaaccccgt ctctactaaa 19980

aatacaaaat tagccagtca tggtggcaca tgcctgtaat cctagctact caggaggccg 20040

aggcaggaga atcgcttgaa ctcaggaggt ggaggttgcg gtgagccgag atcccgccat 20100

tgcacattgc actccagcct gggcaacaag agcaaaactc catctcaaaa aaatagatac 20160

atattttaat ggaaatttta gaattgaaaa atacagtaac caaattgaat ggaaagacaa 20220

catagaatgg agggggcaga caaaataatc agtgaacttc aacagaaaat aatagaaatt 20280

acccaatatg aagaacagaa agaaaataga ctggccaaaa aataaagaag aaaaaagagg 20340

agcagcagga ggaatgatgg aaaaagagaa aggaaggaag gaagggaagg agggagggaa 20400

ggagtgaggg agaaagtctc aaagacctct gagactaaaa taaaagatct aacacttgtc 20460

atcagggtcc aggaaagaga caaagatggc acagctggaa acgtattcaa aaaataatag 20520

ctgaaaactt cccaaatttg gcaagagaca taaacctata gattcgaaat gctgaacccc 20580

aaataaaaag cccaataaaa tccacaccaa aatacatcat agtcaaactt ctgaaaagac 20640

gaaaagagaa aacgtcttga aagcagtgag tgaaacaaca cttcatgtat aagggaaaaa 20700

caattcaagt aacagatttc ttacagaaat taaggaagcc agaaggaaat gacacaatgg 20760

ttttcaagtg ctgaaagaaa agaagtgtca acacaaaatt ctagattcag taaaaatatc 20820

cttcaagaat caatgggaaa tcaagacagt ctcagataaa gcaaaataag agaatatgtt 20880

gccagcagat ctcccctaaa ggaatggcaa aaggaagatc atgcaacaga ccaaaaaatg 20940

atgaaagaag gaatccagaa acatcaagaa gaaagaaata acatagtaag caaaaataca 21000

tgtaattaca ataaaatttc tatctcctct taagacttct aaattatatt gatggttgaa 21060

gcaaaaatta taaccctgtc tgaagtgctt ctactaaatg tatgcagaga attataaatg 21120

gggaaagtat aggtttctat acctcattga agtggtaaaa tgacaacact gtgaaaagtt 21180

acatacacac acacacgtaa gtatatataa atatatgtgt gtatatgtgt gtgtatatat 21240

atatatacat ataatgtaat acagcaacca ctaacaacac tatacaaaga gataataacc 21300

aaaaacaatt tagataaatt gaaatggaat tctaaaaaat attcaaatac tctacaggaa 21360

gacaagacaa aaagagaaaa aaagaggagg acaaactaaa ttttttaaaa acataaataa 21420

aatggtagac ttaagcccta acttatcaat aattacataa atgtaaatga tctaattata 21480

tcaattaaaa gacagagata gcagagttaa tttaaaaaca tagctataag aaacctgctt 21540

tgggctgagt gcagtgactc acacttgtaa tcccagcact tcgggaggcc aaggcgggtg 21600

gatcacctga ggtcaggagt tccagaccag cctggacaac atggtaatac cccatctcta 21660

ctaaaaatac aaaaaaatta gccaggcatg gtggcacacg cctgtagtcc caactactca 21720

ggaggctgcg acacaagaac tgcttgaacc cgggcagcag aggtagcagt gggccaagat 21780

tgcgccactc cagcctgaac gacagagtga gactccacct cagttgaaaa acaaaaaaga 21840

aacctgcttt aaatatacca acatatgttg gttgaaatta aaagaataaa atatatcatg 21900

aaaacattaa tcaaaagaaa ggagtggcta tattaataac ataaaataga cttcagagaa 21960

aagaaaattt caagagacag gaataaaagg atcaagaaaa gatcctgaaa gaaaagcagg 22020

caaatcaatc attctgcttg gagattcaac accctctctt aacaactgat agaacaacta 22080

gacaaaaaaa tcagcatgga gttgagaaga acttaacacc actgaacaac aggatctaat 22140

agacatttac ggaacactct acccaacaat agcaaaataa acattctttt caagtattca 22200

ctgaacatat ccttagaccc taccctgggc cataaaacaa agctcactag tgattgccga 22260

aggcttggat ggacagtgga agagctgcat ggggagggag aaggtgacag ttaaagagtg 22320

taggatttct ttttgggata atgaaaatgt tccaaaattg attgtggtga tgttggcgca 22380

actctacaaa tataaaaaag gccattgaat tgtacgtttt aagtgggtga aacatatggt 22440

atgtggatta tatctaacgc tttttaaaaa cttaacacat ttcaaagaat agaagtcata 22500

cagagtgtgc tctactggaa tcaaactaga aagaggtaac tggaggataa cgagaaaagc 22560

ctccaaatac ttgaaaactg gacagcacat ttctaaaatc atccgtgggt caaagatatt 22620

catttctgat attcattttt attgtttaat gtatttttaa aaatttctta agggaaataa 22680

actgactaaa aatgaatatg gctgggtgcg gtggctcacg cctgtgatcc cagcactttg 22740

ggaggccgag gctggtggat cacaagatca ggagttcgag accagcctgg ccaagatggt 22800

gaaaccccgt ctcaactaaa aaactacaaa aagtagccaa gcgcagtggc gggagcctgt 22860

ggtcccagct acttgggagg ctgaggtagg agaatcgctt gaacacaggc agcagaggtt 22920

gcagtgagcc aagattgtgc cactgcacgc cagcctgggc gacagagact gcctcaaaaa 22980

aaaaaaaaaa aaaaagaata tcaaaatttg tgggacatag ttaaagcaat gctgagaggg 23040

aaatttataa cactaaatgt ttacattaga aaagagaaaa agtttcaaat caatagtctc 23100

cactcccatc tcaagaacac agaagatgaa gagcaaaata aacccaaagc aagcaaaaga 23160

aagaaaatat aaaaataaat cagtaaaatt gaaaacagaa acacaataaa gaaaatcagt 23220

gaaacaaagt actgattctt cgaaagatta ataaaattga caaacctcta gcaaggctaa 23280

caaacaaaaa agaaagaaga cacggattac cagttattag aatgaaagca taattagaaa 23340

caactctaca cattataaat ttgacaatgt agatgaaatg gactaattac tgaaaaaaca 23400

caaattacca caactcaccc aatatgaaat agataattgg gatagcctga taactactga 23460

gaaaattgaa tttgtaattt taacactctt aaaacagaaa cattaaactt aatattttat 23520

aaatattaga taaggtaatt atacccttcc ttaacaaata aaaacgacaa attattttgc 23580

agctaaagag atgtatgtac tgtgaaaaat atcttcagaa aaatagaact ttgtttgaag 23640

aataaggatt taaaaaatgt ttttaactct caagaagcaa atatctgggc ccagatggtt 23700

tcactgaaga attctaccaa atgtttaatg aagaattacc accaactcta catagcatct 23760

ttgagaaaac tgaagagaag ggaacatctc ccagttcatt ttatgaagtg ggtgttactc 23820

tgatactaga actgtataag gacagctact cttgacacac tgcctatggg tagctctgct 23880

ctgcaggaac agtcagaaaa aaaaaaaaaa gaagcactgg acaagggcag tataaaaaaa 23940

gaaaactggg ccaggtgcag tggctcacac ctgtaatctc agcactttgg gaggctgacg 24000

ctggtggatc acctgaggtc aggagtttga gactagcctg gccaacatgg taaaaccctg 24060

tctctactaa aatacaaaaa ttagccaggc agggtggtgg ggaaaataaa aaggaaaaaa 24120

aaacaaaaat aaactgcaga ccaatatcct tcatgagtat agacacaaaa ctccttaaac 24180

tccttaacaa aatattagca agtagaagca atatataaaa ataattatac accatgatca 24240

agtgggactt attccagaaa cgcaagtctg gttcaacatt tgaaaacaag gtaacccact 24300

atatgaacgt actaaagagg aaaactacat aatcacatca atcaatgcag aaaaaagcat 24360

ttgccaaaat ccaatatcca ttcatgatac tctaataaga aaaataagaa taaaggggaa 24420

attccttgac ttgataaagc ttacaaaaga ctacaaaagc ttacagctaa cctatactta 24480

atggtgaaaa actaaatgct ttcccctacg atcaggaaca aagcaaggat gttcactctc 24540

attgctctta tttaacatag ccctgaagtt ctaacttgtg caaaacgata agaaagggaa 24600

atgaaagacc tgcagattgg caaagaagaa ataaaactgt tcctgtttgc agatgacatg 24660

attgtctcat agaaaatgta aagcaactag gggtaggggg gcagtggaga cacgctggtc 24720

aaaggatacc aaatttcagt taggaggagt aagttcaaga tacctattgc acaacatggt 24780

aactatactt aatatattgt attcttgaaa atactaaaag agtgggtgtt aagcgttctc 24840

accacaaaaa tgataactat gtgaagtaat gcatacgtta attagcacaa cgtatattac 24900

tccaaaacat catgttgtac atgataaata cacacaattt tatctgtcag tttaaaaaca 24960

catgattttg gccaggcaca gtggctcata cctgtaatcc cagcatttta ggaggctgag 25020

gcgagcagaa aacttgaggt cgggagtttg agaccagaat ggtcaacata gtgaaatccc 25080

gtctccacta ataatacaaa aattagcagg atgtggtggc gtgcacctgt agacccagct 25140

acttgggagg ctgaggcacg agaattgctt gaacaaggga ggcagaggtt gcagtgagct 25200

gggtgccact gcattccagc ctggtgacag agtgagactc catctcaaaa aaaataaaat 25260

aaagcatgac ttttcttaaa tgcaaagcag ccaagcgcag tggctcatgc ctgtaatccc 25320

accactttgg gaggccgagg caggcagatc acaaggtcag gagtttgaga ccagcctgac 25380

caacatggtg aaaccccatc tctactaaaa aatatataaa ttagccaggc atgtgtagtc 25440

tcagctactc aggaggctga ggcaggagaa tcacttgaac ccggaggcag aggttgcagt 25500

gttgagccac cgcactccag cctgggtgag agaacgagac tccgtctcaa aaaaaaaaag 25560

caaaataacc taattttaaa aacactaaaa ctactaagtg aattcagtaa gtctttagga 25620

ttcaggatat atgatgaaca tacaaaaatc aattgagctg gacaaaggag gattgtttta 25680

ggtcagtagt ttgaggctgt aatgcacaat gattgtgcct gtgaatagct gctgtgctcc 25740

agcctgagca gcataatgag accacatctc tatttaaaaa aaaaaaaatt gtatctctat 25800

gtactagcaa taagcacatg ggtactaaaa ttaaaaacat aataaatact gtttttaatt 25860

gcctgaaaaa aatgaaatac ttacatataa atctaacaaa atgtgcagga cttgtgtgct 25920

gaaaactaca aaacgctgat aaaagaaatc aaagaagact taaatagcgt gaaatatacc 25980

atgcttatag gttggaaaac ttaatatagt aaagatgcca attttatcca aattattaca 26040

caggataaca ttattactac caaaatccca gaaaaatttt acatagatat agacaagatc 26100

atacaaaaat gtatacggaa atatgcaaag gaactagagt agctaaaaca aatttgaaaa 26160

agaaaaataa agtgggaaga atcagtctat ccagtttcaa gacttacata gctacagtaa 26220

tcaagactgt gatattgaca gagggacagc tatagatcaa tgcaaccaaa tagagaacta 26280

agaaagaagc acacacaaat atgcccaaat gatttctgac aaaggtgtta aaacacttca 26340

acgggggaag atatgtctct cattaaaggg tgtagagtca ttgcacatct ataggcaaaa 26400

agatgaacct gaacctcaca ccctacagaa aaattaactc aaaatgactc aaggactaaa 26460

cataagatat acatctataa aacatttaga aaaaggccac gcacggtggc tcacgctcgt 26520

aatcccagca ctttgggagg ccaaggcagg tggatcacct aaggtcagga gtttgagacc 26580

agccggatca acatggagaa gccccatctc tactaaaaat acaaaattag ctggacgtgg 26640

tggcacatgc ctgtaatccc agctacttgg gaggctgagg catgagaatc gcttgaaccc 26700

ggggggcaga ggttgcggtg agccaagatc acaccattgc actccagcct gggcaacaag 26760

agcaaaactc caactcaaaa aaaaaaaaaa aaaggaaaaa tagaaaatct ttgggatgta 26820

aggcgaggta aagaattctt acacttgatg ccaaactaag atctataagg ccagtcgtgg 26880

tggctcatgc ctgtaattcc agcactttgg tcaactagat gaaaggtata tgggaattca 26940

ctgtattatt ctttcaactt ttctgtaggt ttgacatttt tttagtaaaa aattggggga 27000

aagacctgac gcagtggctc acacctgtaa tcccagcact ttgggaggcc ggggcaggtg 27060

gatcacacgg tcaggagttc gagaccagcc tggccaacat ggtgaaaccc cgtctctacc 27120

aaaaatataa aaaattagcc gggtgtcatg gtgcatgcct gtaatcccag ctactgagga 27180

ggctgaggca ggagaatcac ttgaacctgg gaggtggaag ttgcagtgag ccgagattgt 27240

gccactgcac tccagccttg ggtgacagag cgagactccg tctcaaaaga aaaaaaaaaa 27300

aaagaatatc aaacgcttac tttagaaact atttaaagga gccagaattt aattgtatta 27360

gtatttagag caatttttat gctccatggc attgttaaat agagcaacca gctaacaatt 27420

agtggagttc aacagctgtt aaatttgcta actgtttagg aagagagccc tatcaatatc 27480

actgtcattt gaggctgaca ataagcacac ccaaagctgt acctccttga ggagcaacat 27540

aaggggttta accctgttag ggtgttaatg gtttggatat ggtttgtttg gccccaccga 27600

gtctcatgtt gaaatttgtt ccccagtact ggaggtgggg ccttattgga aggtgtctga 27660

gtcatggggg tggcatatcc ctcctgaatg gtttggtgcc attcttgcag gaatgagtga 27720

gttcttactc ttagttccca caacaactgg ttattaaaaa cagcctggca ctttccccca 27780

tctctcgctt cctctctcac catgtgatct cactggttcc ccttcccttt atgcaatgag 27840

tggaagcagc ctgaagccct cgccagaagc agatagtgat gccatgcttc ttgtacagcc 27900

tacaaaacca tgagcccaat aaaccttttt tctttataaa ttatccagcc tcaggtattc 27960

ctttatagca agacaaatga accaagacag ggggaaatca acttcattaa aataatctat 28020

gcagtcacta aacaaataag aacaagaggc tccagaagtg ggaagccaat acccagagtt 28080

cctacaatac agtatctgaa aagtccagtt tccaaccaaa aaatatatat atacaggccg 28140

gacatggtag cttatgtctg taatcccagc actttgggat gctgaggcgg gcagatcacc 28200

ctaggtcagg agttcgagac cagcctggcc aatatggcaa aaccccgtct ctactaaaaa 28260

tacaaaaatt agccaggcat ggtggtggat gcctgtaatc ccagctactc gggaggctga 28320

ggcagggaat cacttgaacc caggaggcag aggttgcagt gagccgagat cacgccactg 28380

aactccagcc tgggcaacaa agtgagactc cacctcaaaa aaaaaaaaaa tatacatata 28440

tatatgtgtg tgtgtgtgtg tgcgcgcgtg tgtgtatata cacatacaca tatatacata 28500

tatacagaca cacatatata tatgaagcat gaaaagaaac aaggaagtat gaaccatact 28560

ttctgtggtt atgataggat ggggtatcac gggggaagta gacaagggaa actgcaagtg 28620

agagcaaaca gttatcagat ttaacagaaa aagactttgg agtaaccatt ataaatatgt 28680

ccacagaatt aaagaaaagc gtgattaaaa aaggaaagga aagtatcata acaatattac 28740

tccaaataga gaatatcaat aaaggcatag aaattataaa atataataca atggaaattc 28800

cggagttgaa aggtagaata actaaaattt aaaattcact agagaaggtt caacactata 28860

tttgaactgg cagaagaaaa atttagtgag acaaatatac ttcaatagac attattcaaa 28920

tgaaaaataa aaagaaaaaa gaatgaagaa aaataaacag aatctcagca aaatgtggca 28980

caccattaat cacattaaca tatgcatact gagagtaccg gaagcagatg agaaagagga 29040

agaaaaaata ttcaaatgat ggccagtaac ttcctagatt tttgttttaa agcaataacc 29100

tatacaatca agaaactcaa tgaattccaa gtaggataaa tacaaaaaga accacaaaca 29160

gatacaccat ggtaaaaatg ctgtaagtca aaaacagaga aaatattgaa agcagctaga 29220

ggaaaactta taagagaacc tcacttacaa aagaacatca cttataaaag aaccacaata 29280

atagaaacag ttgacctctc atcagaaaca atgaatgata acatatttga agtgctcaaa 29340

gaaaaaaaat aaagattcct atatacgaca aagctgtctt tcaaaaatat acatccaaaa 29400

ggattgaaac cagggtcttg aagagttatt tgtacatcca tgttcatagc agcattattc 29460

acaatagcca aaaggtagaa gcaacccaag ggtccatcga caaataaata aaatgtggta 29520

tatgtataca caatggaatt tattcagtat taaaaaggaa tgaaattctg acacatgcta 29580

caacatggct aaaccttgag aacactatgc taagtgaaat aagccagcca caaaaggaca 29640

aataccatat tacttcactt gtatgaaata cctagggtag tcaaattcag agatagaaag 29700

taaaacagtg gttgccaagg gctgagggag ggagtaacgt ggagttattg ttgaatgggt 29760

acagaatttc agttttgcaa gataaaaaga gttctggaga cagatggtgg tgagggtggt 29820

acaacaatac aaatatactt tatactactg aacagtatac ttaaaaatga ttaacatggt 29880

gaaaccccgt ctctactaaa aatacaaaaa aattagctgg gtgtggtggc gggcacctgt 29940

aatcccagct acttgggagg ctgaggcagc agaattgctt gaaaccagaa ggcggaggtt 30000

gcagtgagct gagattgcgc caccgcactc tagcctgggc aataagagca aaactccgtc 30060

tcaaaaaata aaaaataaaa aaaatttaaa aatgattaag caggaggcca ggcacggtgg 30120

ctcacaccta taatgccagc actttgggag gccgaggcag gcgatcactt gagaccagga 30180

gtttgagacc agcctggcca acatggcaaa accctgtctc tgctaaaaat acaaaaatta 30240

gccaggcatg gtggcatata cttataatcc cagctactgg tgagactgag acacgagaat 30300

tgcttgaacc caggaggcag agattgcagt gagtcgagat cgcgccactg aattccagcc 30360

tgggcgacag agcaagattc tgtctcgaaa aaacaaaaac aaaaacaaaa agcaaaacca 30420

aaaaataatt aagcaggaaa cgagattgct gctgaggagg agaaagatgt gcaggaccaa 30480

ggctcatgag agcacaaaac ttttcaaaaa atgtttaatg attaaaatgg taaattttat 30540

atgtatctta ccacaaaaaa aagggctggg gggcaggaaa tgaaggtgaa ataaagacat 30600

cccagagaaa caaaagtaga gaatttgttg ccttagaaga aacaccacag gaagttcttc 30660

aggctgaaaa caagtgaccc cagagggtaa tctgaattct cacagaaaat tgaagcatag 30720

cagtaaaggt tattctgtaa ctatgacact aacaatgcat attttttcct ttcttctctg 30780

aaatgattta aaaagcaatt gcataaaata ttatatataa agcctattgt tgaacctata 30840

acatatatag aaatatactt gtaatatatt tgcaaataac tgcacaaaag agagttggaa 30900

caaagctgtt actaggctaa agaaattact acagatagta aagtaatata acagggaact 30960

taaaaataaa attttaaaaa atttaaaaat aataattaca acaataatat ggttgggttt 31020

gtaatattaa tagacataat acaaaaatac cacaaaaagg gaagaagaca atagaactac 31080

ataggaataa cattttggta tctaactaga attaaattat aaatatgaag tatattctgg 31140

taagttaaga cacacatgtt aaaccctaga tactaaaaag taactcacat aaatacagta 31200

aaaaaataaa taaaataatt aaaatgtttg tattagtttc ctcagggtac agtaacaaac 31260

taccacaaat tgagtggctt aacacaactt aaatgtattt tctcccagtt ctggaggcta 31320

aacacctgca atcaaggtga gtacagggcc atgctccctg tgaaggctct aggaaagaat 31380

cctcccttgt ctcttccagc ttccagtggt tctcagtaac cctaagtgct ccttggcttg 31440

tagctatatc attcctagca accagaaaga agaaaataat aaagattatg gcaaaaaata 31500

atgaaatcaa aaggagaaaa atggaaaaaa ataaataaaa ccaaaagcta gttctttgaa 31560

aagatcaacc aagttaacaa accttttaac tagactgaca aaaaggaggt aagactcaaa 31620

ttactagaat cagaaataaa agaggggaca ttactaatga gggattagaa aagaatacta 31680

cgaacaaatg tgtgccaaca aattagaaaa cttagatgaa atggacaggt tcctaggaca 31740

acatcaacta ccaaaattta ctcaagaaga aagagacaat ttgaatgagc tataacaagg 31800

gaagagactg aattgacaac caagaaacta tccacaaaga aaatcccagg cccagaagat 31860

ttcactgtga aattctttca aacttataaa tataaattaa catcagttct tcacaaactc 31920

ctccaaaaaa aagaacagat ctctatttac aggcgatacg atctttagaa aatcctaagg 31980

gaactactaa gacactatga taactgataa acaagttcag caaggctgca ggatagaaaa 32040

ccaatataca aaaatctatt atatttctat acacttgcag tgaacaaccc aaaaatgaga 32100

ttaagaaaat aattcaattt acaataacat caaaaagaat aaaaacactc aaaaataaat 32160

ttattcaagt aagtgcaaaa cttatactct agaagctaca aaacactgtt aaaagaaatt 32220

aaaggtttac ataaatgaaa aactatccca tgttcatgga tcaaaagact tattactggc 32280

aatgctctcc aaattgatct ataaattcaa caaaatcctt atcaaaatcc cagatgaggc 32340

tgggggtggc ggttcatgcc tgtaatccca gcactttggg aggctgaggc acgcagatta 32400

cctgaggtcg ggagctcgag atcagcctga ccaacatgga gaaaccctat ctcttctaaa 32460

aatacaaaat tagtcaggcg tggtggcaca tgcctataat cccagctact cgggaagctg 32520

aggcaggaga atcgcttgaa cccaggaggc agaggttgca gtgagccaag atcgtgccat 32580

tgcactccag cctgggcaac aagagcaaaa ttccatctca aaaaaaaaaa aaaaaaaatc 32640

ccagatgact tcactgttga aattgaaaag attattctaa aattcacatg gaattgcaag 32700

accttgagaa tagccaaaac aaacttgaaa aacacgaaca aaatatagga tgactcactt 32760

gccaattgca aatgttacga cacagcaaca gtaatcaaga ctgtgtggta ctggcaaaag 32820

acacatacat acatacatat caatggaata taattgagag tacagaaaca agcctaaaca 32880

tctatggtaa gtgcttttct atttttttct tttttttttt cttttttgta gagatagaat 32940

ctcaccatgt tgcccaggct ggtcttcaac ttctgggctc aagcaatcct cccactgtgg 33000

cctcccaaag tgctgggata actggcatga gccaccacat ccagcccaga tgattttcaa 33060

aaaagtcaac aagaccattc ttttcaacaa ataggtctgg gatgatcaga tagtcacatg 33120

aaaaaaaaaa tgaagttgga ccctccatca cactaaagtg ctgcgattat aggcatcagc 33180

caccacatcc agcccaaatg attttcaaaa aggtcaacaa gaccattctt ttcaacaaat 33240

aggtctggga taatcagata gtcacatgaa aaaaaaaatg aagttggacc ctccatcaca 33300

ccatatgcaa aaattaattc aaaaatgaat tgatgactta aacgtaagag ttacgactgt 33360

aaaactctta gaaggaaaca tacgggtaaa tcttaaagac gttaggtttg acaaagaatt 33420

cttagacatg acaccaaaag catgaccaac taaggtaaaa tagggtaaat tgtacctacc 33480

aaaatgaaaa acctttgtgc tggaaaggac accatcaaga aatggaaagc caaaatagcc 33540

aaggcaatat taagcaaaaa gaacaaagct ggaggcatca tactacctga cttcaaagca 33600

acagtaacca aaacagcatg gtactagtag aaaaacagac acatagacca atggaacaga 33660

ataaagaacc caaaaataaa tccacatatt tatagtcaac tgatttttga caatgacacc 33720

ccttcaataa atgatactag gaaaactgga tatcgatatg cagaagaata aaactagacc 33780

cctatctctc accatataga aaaatcaact cagactgaat taaagacttg aatgtaagac 33840

ccaaaactat aaaactactg gtagaaaaca taaggaaaaa cgcttcagga cattggtcca 33900

ggcaaagatc ttatggctaa aacctcaaaa acacaggcaa caaaaacaaa aatggaaaaa 33960

tagcacttta ttaaactaaa aagctcctgc acagcaaagg aaacaacaga atgaaaagac 34020

aacctgtaga atgggagaaa atatttgcaa actatccatc catcaaggga ctagtatcca 34080

gaacacacaa gtgactaaaa caactcaaca gcaaaaaagc aaataatctg gtttttatat 34140

gggcaaaaga tctgaataaa cattctcaaa ggaagacata caaatgtcac tatcattctg 34200

ccagtaccac actgtcttga ttacttgtta gtgtataaat ttttaaattg ggaagtgtga 34260

gtcatcctac actttgttct tgtttttcaa gtttgttttg gctattctgg gagccttgca 34320

agtataaaat agccaacaag tatgaaaaaa tgctcaccat cactaatcat cagagaaata 34380

aaaatcaaga ccactatgag atatcctctc actccagtta gaatggctac tatcaaaaag 34440

acaaaatata atggatgctg gcaaagattt ggagaaaggg gaactcctat acactgtggg 34500

tagggatgca aattggtaat ggccattatg gaaaataata ctgaggtttt tcaaaaaact 34560

gaaaatagaa ctaccatatg atccagcaac cctactactg ggtatttatc caaaggaaag 34620

aagtcagtat actgaagaaa tatatgcact ctcatgttaa ttgcaacact gttcacaaca 34680

gccaagacag ggaataaatc taaatgtgca tcaacagatg aatggataaa gaaaatgtgg 34740

catatacact caatagaata ctattcagcc attaaagaag aatgaaatcc tgtcatccca 34800

gcaacatgga tgaacctgga ggacattata tttaatgaaa taagtaaagc acaaaaagat 34860

aaacagtaca tgttctcact cagacatggg tgctaaaaag aaaatggggt cacagaatta 34920

gaaggggagg cttgggaaaa gttaatggat aaaaatttac agctatgtaa gaagaataag 34980

ttttagtgtt ctatagaact gtagggcgag tatagttacc aataacttat tgtacatgtt 35040

caaaaagcta gaagagattt tggatgttcc cagcacaaag gaatgataaa tgtttgtgat 35100

gatggatatc ctaattaccc tgattcaatc attacacatt gcatacatgt atcaaattat 35160

cactctgtac ctcataaata tgtataatta ttacgtcaac aaaaaaagga aaaaaaagaa 35220

aattaagaca acccacataa tggaagaaat aaaatatctg caaattatat atatctgata 35280

aatatttaat atttataata tataaagaac tcctacaact caagaacaac aacaaaacaa 35340

cccaattcaa aaatgggtaa aagccttgaa tatacactta tctaaagact atatacaatt 35400

ggccaataaa gacacgaaaa gatgctcaac atcactagtc atcagggaaa tataaatcaa 35460

aaccacaatg tagaatgtag acaccacttc atatgcacta ggatggctag aataaaaagg 35520

taataacaaa tgttggtaag gatgtgaaaa aatcagaaac ctcattcgct gctgttggga 35580

atgtaaagtg atgcagccac tttggaaaac agtctggcag ctcctcaaat tattaaatac 35640

agagttaccg tatgacccag gaatattcct cctgggtcta taaccaaaaa aatgaaaaca 35700

tatatccaca taaaaacttg tacatgggca tttatagcaa cattattcat aacagcaaag 35760

gtggtaagaa cccatatgcc catcatctga tgaacaggta aataacatgc ggtattatcc 35820

atacactaga atattatctg cccatacaag gagtgacatc cagctacatg ctacaaggat 35880

gaatctcgga aaccttatgc taagtgaaag aagccagtca caaatgacca cagattatga 35940

ttccatgcat cggaaatgac cagaataggg aaatctatag agacagaaag tagattagtg 36000

gttgggtggg gctgggagga caggtagtac actactttcc cagaactact ggaacaaagt 36060

accacaaact ggggagctta aacatagaaa ttgatttcct cacagttctg gagactagga 36120

ctctgagatc aaggtgtcag cagagctggt tctttctgag ggccctgagg caaggctctg 36180

tcccaggcct ctctccttgg ctggcaggtg gccatcttct ccctgcgtct tcacatcatc 36240

ttttctctgt gtgtgcccat gtccaaattt tgattggctc attctgggtc atggccaatt 36300

gctatgcaca aagtgaagtc tacttccaaa agaagggaag agggaacact gactaggcta 36360

aacttatagt cattttaatg tccgcttttc ctatgagatt gtgaacacac agaagtaggg 36420

tttttatcta cattgtgcaa agtttaataa gaaaaataga attcaagaga agcagttcaa 36480

tagcaggaat ttaatatggg aactaattac aaggtttagg gcaggactaa aaagccagtt 36540

gggatggtga gccaacccag agattagcaa cagtgggacc ccatctacct accacccatg 36600

aagctggaag gataaaggag gggctattat cagagtccac aagccagtgt cagagtcctt 36660

ggctggagct gggaccaccc tagagacact gtgcaaagca gaaaacaagg gggaaaaacc 36720

ctgacttctc ccttcctccc acctttcaat ctcccactag tgcttcctac tagccatact 36780

tggccagaga cagtgacaag gaacactgca aaatgaagtt tgtaggaatc atctccctct 36840

gagacagaga aatatggaag ggtagaaaat gaatcagagg ataaagagaa aaaaccctga 36900

gtactatctt atttatcttt gtatctccag tgcctaatct gtctctcaaa aaaggaaagc 36960

aattgagaga aactgaaaac tccaattgaa atgaaagaat ggagaattac tggactagaa 37020

gagaagagaa aaatttattc cgcatagagt aaacaagaat ggattcacaa aggacgtgat 37080

gaatgaaaag ctataatcag caaagatttg ccagagaaat taaaaagtgg taaactcagc 37140

cacgctgtac aacctgaagg cacaatgcat gaaaacgttt caagaaatga caagatttga 37200

agtcaaattc taagtgcttt tccagaatct ctcaagacga ttatatagct accccatttt 37260

attaaataaa atggaaactt actaaacttt ccccttgtat taaactaaca tatgtcctaa 37320

tagcaaacga ttctggaatt cctagagtaa aatatatttc gtcaaagtgt attgctcttt 37380

taatattctg ctgacctcct tttgctattt aggatatttg tatacacatc acacgtaaat 37440

ttggtctata gtttacatct acgggcttat actgttcttt ttttcatttt tttaaaattt 37500

ccaaccccca gtatccatat actgctctct atcagggtta ttttaacttt gtaaaatcag 37560

ctgagatgct ttccatgttt ttttttttta ttttctgcca catttgaata gcataggagt 37620

taccaccatc aaccttggat tatttaagca ttcacgattc cacgtgtgga ttttttattc 37680

agagtctttc ttgtcattcc tgctatcagc acagaaccca atctcagctt tccagctata 37740

ctctcacccc atggaatttg cagatgaagt tcaaaaggac ctttgcatta tcctgcctcg 37800

ccctcttccc ccttcattta gacatcacct tcttctagaa cgtcttacct gacatgccct 37860

gctcccaacc cctgctgccc aattgtgtgc tctcccgtgt cctggcctgc catcctcttt 37920

agtaattgcc tgctccctca tctgtctccc cacccagaca ttaagctgaa tagactggat 37980

ttgtgtcttg tccatcacta taatctcagc acctagtacc tagtaggtac ttaccatgta 38040

ttcattagca aaatgttatg tataaccttg caccttaaaa acaagagaag gaagacaaaa 38100

ttaagtctta agactatggt ttagaacatg gatcagaaac tacagtctgc agcccaaatc 38160

cagaccaaat gaagagacca tgttcattta catacaacct atagcagctt tcacactaca 38220

ggagcagagc taagtagttc caagggaaca cacggccctg caaagcctaa aatatttact 38280

ctatagctct tcacagaaaa agttttcaga tccctcgttt agaactcttg ttcatatgca 38340

atttcactaa accatagttt tttgggtttg tttggttttt tttggcaaaa aggaatgagc 38400

cgatccagaa aaggttgaaa agaatgaatc attactgctg aaagaatgtg cacacagtcc 38460

gtcagtattc tgctgccatg ctgacaccca tccaatagtg tcatgagatg cagcagctac 38520

tactgtgttc tcaatgccga gtccacccac tccataacca tgtccaagca atcttgggaa 38580

catcatcacc atgcttgttt atccttaagg tattgcctca catacagcag tggctggtca 38640

taaagtcaaa tgacactagt ggccaggagg tcaagagaat gagtgaggac aggtgggtag 38700

gcagcccagg ccctagcaac agcaggagct cacccctcag tcactctagc caggactgaa 38760

atacttttca ccctttcaag agagactagg aatctggatt tttatgtgaa atatcttgat 38820

tactaaatgt tgtcaacaga catgtcaaaa ggtaaaacta agtaagttca tggggcagat 38880

tgactattca ggttatagaa ttaaggattc ttatccaaca cagataccaa ccaaaaagct 38940

gacgtataac atattaggag aaactatgtg cactgtcgaa acatcaacaa ggggctaatg 39000

tctaaaatag tctatattgg attccagttg aaacatgggg aaaggacatg aacaggcaac 39060

ttatgtcaat ggaaactcaa aaagataaca agcatatata aaagcattct caaattcagt 39120

agtaaacaga cagatgcaaa taaaaagagg gaaactgctg ccgggcacag tggctcacac 39180

ctgtaatccc agcactttgg gaggccgagg cgggcggatc atgaagtcag gagatcgaga 39240

ccatcctggc taacatggtg aaaccccgtc tctactgaaa acacaaaaaa ttagccaggc 39300

gtagtggtgg gcaccagtag tcccagctac tcaggaggtt gaggcaggag aatggcatga 39360

acccaggagg cggagattgc agtgagccga gaccatgcca ctgcactcca gcctgggcga 39420

ctgagtgaaa ctccatctca aaaaatataa taataattat aattataata ataataaata 39480

gtaaataaat aaaaagagag agactgctaa agtctagaaa gttgaatgat gccaagcgca 39540

tgcaaagatc agggccttgg gatggccggg tgcagtggct cacgcctgta atcccaccac 39600

tttgggaggc caaggcgggc ggatcatgag gtcaagagat caagaccatc ctggccgaca 39660

cagtgaaacc cggtctctac taaaagtaca aaaaaatata tatatatata tatattatta 39720

tattatatat atatatatca gagccttggg aatccttgtg tgctgctggg gaaggtagtg 39780

gtgcagccac ccttgacagc aatctggcag tacttggtta tattaagtat aggcacacac 39840

cacgaccagg cagtcctact cctgggtcta aatcccaaag aattctcaca caagtccata 39900

aggagacatg tacgaggctc attcagcatt actgggagtg ggaatcaacc tgggtgtcca 39960

tctacaggag acgagatgga caaaatgtgg tggatattaa gaccagaatc accaagtaac 40020

agagatgggt ggtgagtgac aatcctaaga tacagaataa aggctagaac atgatgccat 40080

tcatgtaaat taaaaataga tgcacacaaa gcagtatacg cgtgaccctt gaatagcaca 40140

ggtttgaact gcctgtgtcc acttacatgt ggattttctt ccacttctgc tacccccaag 40200

acagcaagac caacccctct tcttcctcct ccccctcagc ctactcaaca tgaagatgac 40260

aaggatgaag acttttatga taatccaatt ccaaggaact aatgaaaagt atattttctc 40320

ttccttatga ttttctttat ctctagctta cattattcta agaatatggt acataataca 40380

catcacacgc aaaataaatg ttaattgact gtttatatta tgggtaaggc ttccactcaa 40440

cagtaggctg tcagtagtta agttttggga gtcaaaagtt atacacagat tttcaactgt 40500

gcaggcaatc agttcccctg accccctcat tgttcacggg tcaactgtat atacacaaaa 40560

gtattatatg aacctcatta gaatagctgt ctatagggag aagagaatga gagtgggata 40620

aaacggaatg aacaaataaa ccaacaaatg cattaacaag caaaacaaca gaggggcttg 40680

catgggccag tgatgataaa gggctaagaa tgagaatata attaattcaa ttcctcacac 40740

ctgaggtcta aaaccaagga aagggagggc caggcgtgga ggctcacgcc tgtaatccca 40800

gcactttggg aggctgaggc gggcggatca caagattagg agtttgagat cagcctggcc 40860

aacacagtga aagcccatct ctacaaaaaa tacaagaatt acccaggtgt ggtggcacat 40920

gcctgtagtt agctactctg gaggctgagg caggagaatc acttgaaccc aggaggcgga 40980

ggttgcaggg agccgagatc acaccattgc actccagcct gggtgacaga gtaagactct 41040

gtctcaaaaa aataaaaaaa ataaaaaaac agagaaaggg aggaaactag atccaggctg 41100

actagataca gcctttagag ttagaaaaga tgatttgaca atctaagccc acactcagat 41160

tgaatgaaat tgaaaagcct ttcaaactaa aacatttaat tacaccatct gctgcagaca 41220

gaactcagac aactcaaaca ggtaatgtca gcgtggtgtt ttatatcacc accctcaaca 41280

cagaataaaa atcagctgca tgtgaagcag tgactagaat gaagaaaagg ctgcttctta 41340

cttccttcta gtggttcttt ccgaaaacat taataggcac cagctctatg catgtcaccc 41400

tgcagggaga catggggtat ataactatga cttactgttc attcctcaag gaattcccaa 41460

tcttgtggaa gattatacac aatgaggcaa caaaaactat ccaataaaac cacggaaaag 41520

aagccagtga caaagaagcc agtgatgaaa ggccctgtga gcagagctga tggccatttg 41580

gggaagaaag accaacatgg atgggggtga tcagggtggc tccgtgggaa agctggaaga 41640

gaagtggcag atctctgagc tggatgatgg gccactacca tctgtatatg gctaattaaa 41700

gaccatgtgt ggatttttta ttcagctctt tcgtgtcatt cctgctatca gcacagaacc 41760

caatctcaac tttccagcta tattgagcta aacttctcac ctcatggaat ttgcagataa 41820

agttcaaaag gatccttgcc ttttcaaaat aattttgaat ggttgagtag tccctctgtg 41880

ctctctcact gacaccctct caaggctgct gagcacgtgc catgctatgg ctttctccaa 41940

catcaggaaa tgttctccac tcagtttcac cttaatacaa atgtgttctc tcttcagaga 42000

aggcaaaaaa attcatgacc atctgactgg gagaagtcat ttctaggtaa agtgtccatc 42060

tttttctgag gaacacagga ggaaaatctt acagaaaaga gttaacacag caggcctaag 42120

actgcttttt aaaataaata aataaataaa taaataaata aataaataaa taaataaata 42180

aataaatgaa tgatagggtc ttctgtattg gccaggctag tctcaaattc ctggcttcaa 42240

gagatcctcc caccttggtc tcccacagtg ttgggattat agacatgagc cattgtgctt 42300

ggcccaagac tgttattctt aaaaagtctc ataaaaagca tggttaatcc ttggctggca 42360

cctgggaact tagatttcag aagggttccc accatccaac ctggaaagag ggactcactg 42420

tgcctaaatt attgtgtggt ttatgctgaa ctcctgcttt tcttcaggta gcgtggaatg 42480

tggtatgtgc tgggcaaagg gggcctgcat gaccagcccc caataaaaac cctgggtgtt 42540

gggtctctag tgagtttccc tggtagacag catttcacat gcgttgtcac agctccttcc 42600

tcggggagtt aagcacatac atcctgtgtg actgcactgg gagaggatgc ttggaagctt 42660

gtgcctggct tcctttggac ttggccccat gcacctttcc ctttgctgat tgtgctttgt 42720

atcctttcac tgtaataaat tacagccgtg agtacaccac atgctgagtc ttccaagtga 42780

accaccagat ctgagcatgg tcctgggggc ccccaacaca gaaataaatt ataaaagacc 42840

aaggactggg catggtggcc catgccggta atctcagcgc tttgggaggc cgaggcagga 42900

ggaccagtta agcccaaaag ttcaaagtta cagtgaccta tgactgcgcc aatgcactct 42960

aacctgggag acagagcaag accctgtccc caaaacaata aactaaacac atacttctgc 43020

cttccaagtg tcttaaaatt caatggaatg gtagaaacat ttttaaaaca ctaaatcaaa 43080

agaaacctgg aaaacaagag tgccgatggc caactaaaat gtctaggaaa tttctgaaaa 43140

gtaaaaagta ctcagaacca gattacctga gcaaaccata gcccaataca agcttgggag 43200

gaggctgtta tgcagaagga aatggtaaca ggtttccagg aacagacttg taacagcaga 43260

tagaacagca gaggtagaac ctgacaaggt gattacctgg ggaactgcag tctgaatgac 43320

caggactgtt ggacccttcc cctcacatgg aatacacacg ccactcagca gcacaccaca 43380

gctcttcaac aatcacagga ggcacgctac gcctagtaag acaggaaaaa aggaattctc 43440

aaacttcgaa gatgaacaca taaagaatca ccaagttttt attcagtatg atgaaacagg 43500

gacactgaat caacagaaca caaacccaag caaagataat tactagagca catagaagaa 43560

attattagat attcttggga agacctaagg ggacattata aagagcaagc agttggtatg 43620

tgacgatctt tgtgatatac caagaaataa aaacacagga tgaagaccag atagagaata 43680

atgctactat ttgtgcaaaa aaggagaaat ggagaatctg attcatattt gcttgtattt 43740

gcatgaagaa actttggaag gtacataagt aactaacaac aatggttacc tacttgtaag 43800

gcgagagaag taagaggaca ggaatggtgg gaacaccttt tgtgtccgga attggtgggt 43860

tcttggtctg acttggagaa tgaagccgtg gaccctcgcg gtgagcgtaa cagttcttaa 43920

aggcggtgtg tctggagttt gttccttctg atgtttggat gtgttcggag tttcttcctt 43980

ctggtgggtt cgtagtctcg ctgactcagg agtgaagctg cagaccttcg cggcgagtgt 44040

tacagctctt aagggggcgc atctagagtt gttcgttcct cctggtgagt tcgtggtctc 44100

gctagcttca ggagtgaagc tgcagacctt cgaggtgtgt gttgcagctc atatagacag 44160

tgcagaccca aagagtgagc agtaataaga acgcattcca aacatcaaaa ggacaaacct 44220

tcagcagcgc ggaatgcgac cgcagcacgt taccactctt ggctcgggca gcctgctttt 44280

attctcttat ctggccacac ccatatcctg ctgattggtc cattttacag agagccgact 44340

gctccatttt acagagaacc gattggtcca tttttcagag agctgattgg tccattttga 44400

cagagtgctg attggtgcgt ttacaatccc tgagctagac acagggtgct gactggtgta 44460

tttacaatcc cttagctaga cataaaggtt ctcaagtccc caccagactc aggagcccag 44520

ctggcttcac ccagtggatc cggcatcagt gccacaggtg gagctgcctg ccagtcccgc 44580

gccctgcgcc cgcactcctc agccctctgg tggtcgatgg gactgggcgc cgtggagcag 44640

ggggtggtgc tgtcagggag gctcgggccg cacaggagcc caggaggtgg gggtggctca 44700

ggcatggcgg gccgcaggtc atgagcgctg ccccgcaggg aggcagctaa ggcccagcga 44760

gaaatcgggc acagcagctg ctggcccagg tgctaagccc ctcactgcct ggggccgttg 44820

gggccggctg gccggccgct cccagtgcgg ggcccgccaa gcccacgccc accgggaact 44880

cacgctggcc cgcaagcacc gcgtacagcc ccggttcccg cccgcgcctc tccctccaca 44940

cctccctgca aagctgaggg agctggctcc agccttggcc agcccagaaa ggggctccca 45000

cagtgcagcg gtgggctgaa gggctcctca agcgcggcca gagtgggcac taaggctgag 45060

gaggcaccga gagcgagcga ggactgccag cacgctgtca cctctcactt tcatttatgc 45120

ctttttaata cagtctggtt ttgaacactg attatcttac ctattttttt tttttttttt 45180

tgagatggag tcgctctctg tcgcccagac tggagtgcag tggtgccatc ctggctcact 45240

gcaagctccg cctcccgggt tcacaccatt ctcctgcctc aacctcctga gtagctggga 45300

ctacaggcaa tcgccaccac gcccagctaa ttttttattt tatttttttt ttagtagaag 45360

cggagtttca ccatgttagc cagatggtct caatctcctg acctcgtgat ccatccgcct 45420

cggcctccca aagtgctggg attacagacg tgagccactg cgccctgcct atcttaccta 45480

tttcaaaagt taaactttaa gaagtagaaa cccgtggcca ggcgtggtgg ctcacgcctg 45540

taaccccagc actttgggag gccgaggcgg gcggatcacg aggtcaggag atcgagatca 45600

tcctggttaa cacagtgaaa ccccgtcgct actaaaaata caaaaaatta gccgggcgtg 45660

gtggtgggca ccggcagtcc tcgctactgg ggaggctgag gcaggagaat ggcgtgaacc 45720

tgggaggcag agcttgcagt gagccgagat agtgccattg ccttccagcc tgggcgacag 45780

agcgagactc cacctcaaaa aaaaaaaaaa aaaatagaga cccggaaagt taaaaatatg 45840

ataatcaata tttaaaaaca ctcaagagat gggctaaaga gttgacggaa caaatctaaa 45900

tattagattg gtgacctgca aaaccagccc aaggaacatc ccagaatgca gcccataaag 45960

ataaagagag catttccgct gggcacagtg gtatggcagg ggaattgcct gagtccaaga 46020

gttgcaggtc acattgaacc acaccattgc actccaggcc tgggcaacac agcaatactc 46080

tgtctcaaaa aaaaaaaaaa ttaaattaaa aaagacagaa tatttgagag aaaaaaatgc 46140

ttatttcaag aaacatgaaa gataaatcaa gatattctaa ttcccaagta agaataattc 46200

cagaagcaga aaatagaata gaggcaagga aacactcaaa acttctccag tgccatagaa 46260

atgtgtatta atctttagaa tgaaacggac taccaaatgc tgagcaggaa gaacaaaaga 46320

gatccactct taagccagtg tggtgcccaa gcgcagtggc tcatgcctgt aatcccagca 46380

ctttgggagg ccgaggcagg tggatcacct gaggtcagga gtttgagatc agtcaggcca 46440

acatggtgaa accctgtctg tactaaaaat acaaacatta gctgggtatg gtggtgcaca 46500

tctgtaatcc caactacttg ggaggctaag gcaggagaat cacttgaaac caggaggtgg 46560

aggttgtagt gagccgagat catgccacac tcccagcctg ggtgacagag caagattcca 46620

tctcaaaaaa aaaatccact cctagacaaa taatagttaa attttagaac accaaggaga 46680

aagaaaaaaa attgtaaagc ttcagagaaa ataaacatta actacaaaga aacgagagtc 46740

agacgcgtgc acttcttcct agataccagc agataaagca atatctccaa aattcagaag 46800

gttttaacgt agaatcctat acccagtcaa gaatattcac atggaaaagt gaaataaaaa 46860

acattgttta aacatgcaag ggttcagaaa gtttaccatt cacagaatcc ctgaaaacaa 46920

aaccaaataa tcacttaagg actcattaag aaaacaaatg aaataaaagc accaatgatg 46980

agtaaataat cagaaaaatt tacagtttac ctaaataact gtttatgcat aatgtatgaa 47040

aacccaaaaa tttaatatgg gacagaatta aaatcatgat aagattcttt tttgctttac 47100

tcatggagag ttcacataaa cagattatct tttaatagca agagaaaaaa atgtttagat 47160

atgtgtgaaa aactaagggt accaaaacag tgcaaattca tttatcatca ggaaaatcca 47220

aattaaaacc acagtatcca ccagaataac taaaaggtaa aagacagaaa ttaccaagag 47280

ttggcaagaa tgtggagcaa ccacatatac ttctggggta aataagttgg tgcaaccggt 47340

actgaaaact gtttgctagt atctactaaa accgagcaca tgcacagact acaaccaagc 47400

agttccactc ccagatacac actcaacaga aatgcacaca ctcactcaac aaaagacgtg 47460

tactagagtg ttcatgtact tactattcat aatagtccaa aaatgcaaac aaccaactgc 47520

caatcaaagt caaatgtata tctatattag ggatatatac aatggcatat acacagcaat 47580

gagaatgaaa tgaaccagct cggcacagtg gttcatgcct gtaatctcag cactttgggc 47640

gggtaaggca ggcagatcac ttgaggtcag aaatttgaga ctagcctggc caacacggtt 47700

aaaacctgtc cccactaaaa acacaaaaat tagccgggca tagtggttgc aggcctgtaa 47760

ttccagctac tcgggaggct gggttgggag aatcgtttga acccgaaagc cggaggtcgc 47820

agtgagcgga gatcgtgcca ctgcactcca gcctggacga tagagcaaga ctccgtctca 47880

aaaaaggaaa tcaaaaatat aaaataagat gacaggaata atccgcaaaa gatcagtaat 47940

caaaataaat ataaatgggc taaagctacc tattaaaaga caaagatttc acacccataa 48000

ggatagctac tatcaaaaaa agagagagaa taacagatgt tagcaaggat gtatggaaac 48060

tgaaattctc acgcattgct ggtgagaata taaaatggtt cagcctctgc ggaaaacact 48120

atgctgggtc atcaaaaaat taaaaataga agtactactt gatccaacaa ttctacttct 48180

gggtatatac ccaaataact gaaagcaggg tcttgaagag atatttgtac acccatgatc 48240

atggcagcat tattcataat agctatgatg tggaaccaac ataaatatcc tttgataaat 48300

atatggataa gcaaaatgtg gtgtatacat tcaatggaat attaattagc aataaaaatg 48360

aagaaaattc tgacacatgc tacaacatgg atgaaccttg agggcattac attaaatgaa 48420

ataagccagt tataaaaaga caaatactat atgaggtact atattagata ctcatgcaag 48480

gtacctaaaa taggcaaatt catagagaca aaaagcagaa tggtggttgc caggggctgc 48540

ggtaatggat acagagcttc aattttgtaa gatgaaaaaa ttctggagat tggttgcata 48600

acaatgtgca cacacttaac actggggaac tgtaaactta aaagtagtaa atggtaaaaa 48660

taaaaataat aaataataaa ttttatgtta ttttaccaca atatttatta aaagacaaag 48720

attaactaat taaacaaaat ccagccataa gctaatggta agagtaacaa ttaaagaaga 48780

cacagaaaat tgaaaatcag tgactagaaa aagatattcc atataaatgc taacaaaaag 48840

caagtacagc aatataaaga gaatgaacaa aaaaaaaatt aaataagatg gctcgtttat 48900

tcccaaaagg tacaattcac caagaagata caagaattgt gaacctttaa gcacataaaa 48960

cagcttcaaa aatacaacat ttaaagaaaa atatatatta aacatagaaa tagtacaaaa 49020

acccctacaa gaatcataat gggagtcttc aatacaactc tccatatcaa caggtcaaac 49080

agagaaaaaa aataagttaa ggatgcagaa aacctgaatt accatcaata aacttgagat 49140

taatatagaa ctgtataccc aatatactaa gagttcaggg aacagtcgtg actgacagtg 49200

gactgcaaat taatctgttc ttaatctttg tttttctttc agcactgtgg cagaatagag 49260

atcctaaaaa ccttccagct acaaaacatc tttttaaaaa tataaaaaaa tacaaaaata 49320

actctgaaat caatagaaga cacatggtga aaccaaaatt ctagaataca gggagaataa 49380

aggcattttc agatattaca aaaacagaaa attgatcatt gctgaagtaa tttctaaaga 49440

atgtacttga gggagaagaa aaatgttcca aagaaaagta tctgtgatac aagaaggaat 49500

ggaaagtgaa gaaatggtaa acaggtagat aaagctaata aatgttgacc tagaaaataa 49560

caaaaacaat agcaataatg tctcgttgga agggttgaag taaaaataca attaaggcca 49620

aatgtgaggt aagtggaatg aaagaattag aagtccttgc cttgttcaca ggactgatta 49680

aataaatgag ccaggttttc cattcaaaca gttaaaactt gaacaaaata aactcaaatt 49740

aagtagaaag ataaaaaaca gaaattaatg tcatagaaaa ataaaaaatc aatagaatta 49800

atcaataaat cctggttaat aaaagctggt tctttgaaag gattaataaa ataatcatta 49860

agcaagtctg atcaaaaaaa aagagaaaag gtaccaaaaa aagtactgta tcagaaagag 49920

aacatacaga tacatacaga tatgtaagag tctgttttct tacaccagaa tactatatac 49980

aacattatgc tagcatatat taaatttcaa taatgttaat gattttctag gaaaacagaa 50040

aatattaaat ttactttgaa gaaacagaaa aactgagaaa aataaatgat catgaaaaaa 50100

atgaaaaggt aattaaatac tgatattaac tgcctaaaca acaccagcag cagcccaggc 50160

agtctgcagt caagttctgc caaacttgag ggaacagata attcttctat tccagagcat 50220

agaaaatgat ggaaagtttc ccaatttaat cagagaggac agcctgatcc ttgttatgaa 50280

cacagataaa aatggggtaa actatatgcc aaactcagat accaaaaccc taaataagat 50340

gctagcttat tgatgtgaac aatccaaaag tgcattttaa attagcccag ggttttagag 50400

aaagaaaatc tagcaatgtg accaccactt atgttaacaa ttttaagacg aaaatctaca 50460

tgatcatatc aatgcatgct acacaaaagc atttgggcaa aaaacccaac acccaccctt 50520

gactttttaa actcttagta attaggcata aacagaaatg tacttaatgt gatagaatac 50580

actcggtgaa gatacagagg gaatgctccc taaaaccaag cccaagacaa agattcctat 50640

ttaacctcaa tagtcaacac tgcagcgaga gtaatctatg gaagacaagg aaaaaagtaa 50700

aaacatgaga gacatctgtt gtttaacaga caataagatc acctacttgg aagaggcaaa 50760

cgaatcaagc gaaaaactat taaaactgag acaggcttta gtatggaggc tcagcttcag 50820

ctgtagtttg ggctaccaaa ttcaactcgc ttgcttggag agttaatcct gcaaagctaa 50880

tttctgttga ggtattagga ttgacaagcc tgtgctcctc cctcctcccc catcttcaac 50940

actgaaataa cacggtgttt ggaactggat aacagaatct tccaaaaaca aaaattgtcc 51000

tgaagggctg acttgtgccc ttactcaaaa aacactttat ctgctgcctg cagctcctac 51060

agttgctggt ggataagcct gccaaccagc tcggcgtaat tcttcctgca gagggcaagg 51120

aagagcactt tcacaggaaa atttttttcc gaactgtatg ccgcttatta cataaactta 51180

cgtgctggca aatggagctc cagcaaaata agatattcag agtcaaactt ccttaggaaa 51240

aaaaaaaaaa aaaagcaagc acataacact aatttccttg catgggcact ggggaaggag 51300

gtcgttactt ccgcacgccc gcaggtccgc accaccggga aacccacggg caccgcgcgc 51360

tgcccccggg ccttccaggt gcactgcgcc gcggcgcccc agctgacccg ggatgcgcag 51420

ccctagccct tcccctgtca ccccggccag gaaggggcgg gagcgcggcg gacgccgagg 51480

gcgaagggct tctcggtcct ctgcaccacg cagcaccccc aaggcacaac agggagggtg 51540

cgggaggctc ccgagaccca ggagccgggg ccgggcgtgc ccgcgcacct gtcccactgc 51600

ggcgagggct ggggtcgcct ccagggccgc agctgtcggg agccacctgg ctctcagtcc 51660

cgggtccctg cgacaaccct cgggcccgga ggggaggagg cggccacctg ccgctgccac 51720

ctgcggcacc ggtcccaccg ctccgggccg ggcaggacag gccaggacgt ccctcctggg 51780

ctggggacag gacacgcgac gaggggaccg gggcccccgc ggcgaagacg cagcacgcct 51840

tcccagaaag gcagtcccgt gcccccacga cggactgccg gacccccgcg ctcgcccgcc 51900

catcccttca gaccacgcgg ctgaggcgca aagagccggc cggcgggcgg gctggcggcg 51960

cggctagtac tcaccggccc cgctggctca gcgccgccgc aacccccagc ggccacggct 52020

ccgggcgctc actgatgctc aggagaggga cccgcgctcc gccggcgcct ccagccatcg 52080

ccgccagggg gcgagcgcga gccgcgcggg gctcgctggg agatgtagta cccggaccgc 52140

cgcctgcgcc gtcctccttc agccggcggc cgggggcccc ctctctccca gctctcagtg 52200

tctcatctcc ctatctgctc atcctctggt cgcacataat cgatgtttgg gcgtcccaag 52260

ccagatgtgg accccatttc cgcactctac actggaggtt ttctaagggt ggtgcccgga 52320

ccagcagctt cagcctcatc tgggaacttg agaaaatgca gattctccgt cccacccagc 52380

ctattcggtt tttcctgcac taaaaccatg aaggtggggc ccagcagtcc acattctcgc 52440

aagcccgtca agtgattctg aggcgccctc cagtttgaga gctatgctca cggcctcacc 52500

tccgccccgc aaggagcccg gtcttgcctg tggcgctagc cgcacacgga cacctcatcc 52560

tgcggggccc gcccccccgc tgcaccctca ccgcccaacg cctcctccgg gatgcagcgg 52620

aggcgcctgg aagtcggcaa ggtcaacatc cccctcagca tcttccctac cctcacggct 52680

cctcctccag gggtgcctca tggccagggg ttagaaagag ccactgtgtt tcttgacatg 52740

gaagtggcct aagaccttaa tgaaaactgc aggagtggaa tgacagaacc tttggtcata 52800

cttgagggcg tgaagctcaa atgaggagga aggaaaggat ccagggagaa taaccaaccc 52860

tggcaagttg tggcgcccag gtagaggggc gagcctaggc tagcggttct cgaccagggc 52920

cggtgttgcc cctcctcgcc gccccgcgta catttgggga ggtctggaga catttttggt 52980

tgtcatgatg cgggagttgc tactgttgcc taagtgggta gacacgaggg tgctcctcaa 53040

catcctacct gaaggacagg actgccccac aaggaagaat gatccggccc caaataagaa 53100

accctgggct ggtcagcaac aacccctttg ttctgagaag agaggaggaa agaataaaag 53160

aagtggggtg aagttttggt ttggtagagg aaacttgaag acattttcac tggaaaggaa 53220

gagaggaaga ggagggagat gtctgtaagg acgagcaaac cgggtgacag ctgatttcct 53280

catattgaag taatgagtcc tagttataat aaattcctaa taaaaaccca gtttatccct 53340

gcaataaact tgtctttttt ttttaaatat actgcttgat tctgtttgct aatattttat 53400

ttacaggctt tgcattgata tgcaaaaatg agatgggcaa taattttctt tttgaatgtc 53460

taatgttgtt tggtttcaga atcaatgtta tgctcacatc ataaaaaatt tggaaccgag 53520

gcaggaggag tgcttgaggc cagaagttcg agaccagtct aggaaacaca gtgagacccc 53580

cccatctcta caaaaaaaaa aaaagaaaaa aaaatgggca tgtttgcttt ttccttttac 53640

tctgaacaat ttaaggagca ttaaaattat ctattctttg aggtttgatc atttcccagt 53700

taaaaatgtt cctcccagcc tgatgctttc tttggggagg gtaaatcttt taaggctaga 53760

aaagtttctt ctgtggcaat tttattattt acattttaaa aattattcta gagttaattt 53820

tgataaagca tgtatttctt aaaacaaatt atcctttttt tccagatgtt caagtgtatt 53880

tgcataaagt tgaggaaagt agtcttttgt gaatctttta acttctccca aatatcttat 53940

tttgtgtatt tttgcttctt tattttgtta acttttaaaa gtgtattttt ttttcaaaga 54000

atcagctctt aggtttatgt ttttggttat actggagctt ttttcttctt ctttttaaaa 54060

tattttttct cctttatttt ttagacgtat tttgatctaa cgtaatcgga agaaggtaaa 54120

ttagaatctt ttgttactat tgtgttttta tttctcctta tttctctgaa gtcctgcttt 54180

ataaatagta ccatgttatt tgtgcataaa tattcatttg tcttatattc ttgggaattt 54240

tcccacttca tcataaaatg accttccttg tctcatttaa tgtgttcaaa ctttgccctg 54300

aatttaactt tgtctgatat tttaccatcc tgctgaattt tgtttgttac cccaaacaac 54360

ctttgctgtt ttcgtctttt ctgaaccctt tattttaggt aatcccttga attagagcac 54420

taagttttgc tttgtgatta aatctgaaaa tctttatctt gccatagatg agttgagccc 54480

tattcatgtg acagctatat tatgctgttt catagccctt ttggtccttt tttcactctt 54540

gcattgcata ttttgtgttt attgtgtttt gtgtttcttc tgataatttg gaaggtttgt 54600

atttttattc agggagttgc cttataatca tactccgcaa tacacatcgt cctcagtttc 54660

ttcagactgt ctgttaactc cctattctga ataaaaatga cattgtaatt tccctctttt 54720

ttctttaccc cttttcttct cctcacctaa tgtaaatgat tttatccttc tttagtattt 54780

gcttttttaa ttaactacat ttataaatat ctttatcact tgatttttaa atcagctttg 54840

aatgagatat ttggattcct agatataaaa gatgttaatt ataccatttc cacgttagta 54900

ggtttataaa atcatacatt ctgctgtgta accataatcc cacgtttgtt ttagttccac 54960

tcctacagtt aaaagattca gaagtattat taacagttat tttgccatag ttttttcccc 55020

aacccatttt gtggtaagtt atgatcctgc tttagtttct taagaataat ttatagagca 55080

gagtgtggtg gctcacgttt gtaatcccag cactttggga gacaagaggt agaaggatcg 55140

cttgaagcca gcagttcaag accaccctga gcaacatagt gagaccttgt ctctacaaaa 55200

aattttaaaa tttagccaga cgtagtggcg tgtgcctata gtcccagcta ctcaggaggc 55260

tgaggcaaga ggattgctag agcccagaag tttgaggctg cagtgacctc tgattgtgcc 55320

actgcacccc agtctgggca agaaagtgag aacctatctc tttaaaataa caataataac 55380

ttatgaaaat tatattccct gagtttttca tgtttaaaaa tatttgttgc ctttatcctg 55440

taaaagtttg agtataaatt cttgggttat actttattta ttgaagaatg tataagtatt 55500

gtcttctaga attgagtgtt gctgtaatga aaccagaagt cagcctggtt tatttttcct 55560

cagaaatgag gtaattgccg gccggacacc gtggctcatg cctgtaatcc caacactttg 55620

ggaggccgag acaggtggat cacgaggtca ggagattgag accatcctgg ctaacatggt 55680

gaaaccccgg ctctactaaa agtacaaaaa gttagctggg catggtggtg gacgcctgta 55740

atcccagcta cccgggaggc tgaggcagga gaatggcgtg aacctgggag gaggagcttg 55800

cagagagctg agatcgcgcc actgcactcc agcctgggcg acagagtgag actccgtctc 55860

aaaaaaacaa aaaaaaaaca aagaagtgaa gtaattgcca tgatgctcca agaattatct 55920

ctttgtctat gaaatccaga aatctcactg ttatacattt tggaattatt attctgggcc 55980

aatatttcct gggacacaat agattgactc tatagattta attttttttt tttttttgag 56040

acagagtctc actgcaatct cagcttactg caacctctgc ctcacgggtt caagcaattc 56100

tcctgcctca gcctcccaag tagctgggac tacaggcgcg tggcaccatg cctggctaat 56160

ttttgtcttt ttagtagaga cagggtttca ccatgttggc caggctggtc ttgaacgcct 56220

aacctcaagt gatccacctg cctcagcctc ccaaagtgct gggattacag gcgtgagcca 56280

ccatgcccag cctcaattcc tctttctatc tggtaatttt tctgaagttg aaaacatttg 56340

ttctaatacg ttatttcagt gttcttctaa gatgtgtaaa gcaccctatt cccaggtcag 56400

cccccatctt gctagtgagc tcggctggtt cttcacaaga gctctggttt tctcctgctt 56460

aatctcaagt acctctgtca gcctccacct ggtttatgat ttggagtttt ttggtttttg 56520

ttttttgttt ttgacagagt cttactctgt cacccaggct ggagagcagt ggcataatct 56580

cagctcactg caacctctgt ctcccaggtt tgagcgattc tcctgcctca gcctactgag 56640

tagctgggat tacaggcgcg tgccaccaca cccggctaat ttttgtattt ttagtagaga 56700

tggggtttca ccatgttggc cagggtggtc ttgaactcct gacctcaggt aatccacctg 56760

cctcagcctc ccaaagtgct gagattacag gcgtgagcca ccgcgcctgg catggtttgg 56820

agttttaatc tgtagtttta ataaagatag tgcttatgtt tgtgtttctt atatttcttg 56880

gtactcttgg gtaatttgta agatccccat atctacacaa gaagtccatt ttcaattctt 56940

ttcttcagac tgtttatttt attttatttt attttatttt tatgtttgag atggagtctc 57000

gctgtgtcac ttctggaggc tggagtgcag tggcgcgatc tcaggtcact gcaacctccg 57060

tctcccgggt tcaagcaatt ctcctgcctc agcctcccga gtagctggga ttacaggcac 57120

ctgccacttt ttaatttttt tagagacaga gtctcgcttt gttgaccagg ctggagtgcg 57180

gtggtgcaat catggctgac tataacctcc aaatcctggg ctcaagtgat cctcctgcct 57240

cagcctcctg agtagctggg actacaggca catgccacca tgcccagtta attttaattt 57300

ttttgtagag acagggtctc catatgttgc ccaggctggc ctcctactcc tggcctcaag 57360

taatcctcct acctcagcct cccaaattac taggattata agcatgagcc accatgccca 57420

gccttgttct actactttaa tttcatatgt taggtgacca tgtaattgat catccaaacc 57480

aggatactgt aagaatgaaa gaggctgaca gtagtatgat gctgggacta gcattgtgca 57540

ctgagattat ttctgggaaa gcaggagata cggtcaccct acttatagtg tgcttgtctt 57600

tggattgttg aatttggagt ttctatttgc aggcttattt caactgggca gccttgatcc 57660

gccctgccca gcaatgctac cgttctctcc accgggtctc tgggacccct tcagtcacta 57720

tacttagctc agttccccac cctcccactc cctaaaagcg taaccaggaa tcctgcctca 57780

ggtctactgc cgtcttccgt gggctgtttc agttcctatt acccagagtc aaactcccag 57840

cattccctac ctgattccag acttggagtc cagagcttta acctcttcag gccaactccc 57900

cactttgcat ttctgtccct atatcttagt ccatggagat acatttcatg tctttgagtc 57960

tacttacaaa gtaaattttg ctgtttttta attttttttt tgagatggag tcttgccctg 58020

tcacccaggc tgtggtgcaa tgacgccatc tcggctcact gcaacctccg cctcctgggt 58080

tcaagcgatt catctgcctc agcctcccaa gtagctgtga ttacagacag gcaccaccac 58140

gcccagctaa ttttttttat cttttagtag agacagggtt tcaccatgtt ggccaggctg 58200

gtcttgaatt cctgacctcg tgatctgccc atctcggcct cccaaagtgc tgagattaca 58260

ggcgtgagcc actgtgccca gccaattttg ctttttttat atttcattgc tatatgttta 58320

gaggataagt ttacagtgct atatgcattc ccaaatatta gaccaaaaaa atctccaaaa 58380

aattagaaag aaaatccaaa aaatctcaaa aaataccaaa aagcaacaat ctcacagacc 58440

atactcactg acccccaata aaataaaatt agaaattaac cacaacttaa caaaataaag 58500

tactcaagtc agagaggaaa gaggaaataa acatcaaaat tacaaagtct aggcggtggc 58560

tcacgcctgt aatcccagca ctttgggagg ccaaggcggg cagatcacaa ggtcaggaat 58620

tcgagaccag cctggccaat atggtgaaac cccgtttcca ctaaaaatac aaaaattagc 58680

caggcatagt gatgtgtgcc tgtaatccag ccacttggga ggctgaggca ggagaatcac 58740

tgaacccagg gagacgaaga ttgcagtgag ccaaaatcgt gccactgcac ttcggcctgg 58800

gtgacaaagc gagactccat ctcaaaaaaa aaaaaattac aaactcttta gatagaaatt 58860

ttggtgtttt tttttgagac ggagtctcac tctgtcgcag aggctggagt gcagtgggac 58920

tatgtcagct caccgcaacc tccatctcct ggattcaagc aattctcctg tctcagcctc 58980

ccaagtagct aggattacag gcgcccacca ccagacccag ctagttttta tatttttagt 59040

agagatggtg tttcaccatg ttggccaggc tggtctcaaa ctcctgacct caagtgatcc 59100

acctgcttca gcctcccaaa gtgctcagat tacaggcgtg agccaccgca ccccacctag 59160

atagaaattt caacatgagg ccgggcacaa tggctcacgc ctgtaatctc agcacttcag 59220

gaggctgagg cgtgggagga tcacttgggc ccaggagttc aggaccagca tgggtgacag 59280

agacagaccc tgtctctatt tatttgaaaa aaaaaaaaaa aaagagagag agaaagaaat 59340

ttcaacatga aaagtatctc tcaaaccctt cgagatgttg gcaaaaagcg actcaaagga 59400

aaatgtatta ctgtgtgtga atttgcttga aaataagaaa gaggccgggt gtggtggcta 59460

acacctgtaa tcccaacact ctgggagtcc gaatcaagtg gatcatgagg tcaggagatc 59520

gagaccatcc tggctaacat ggtgaaaccc tgtctctact aaaaatacaa aaaattagct 59580

aggcgcggtg gctcatgcct gtaatcccag cactttggga ggctgaggca ggtggatcac 59640

ctgaggtcag gggtttgaga ccagcctggc ctacatggtg aaacctcgtc tcttctacaa 59700

atacaaaaat tagctgggcg tggtggtggg tgcctgtaat cccagctact cagaggctga 59760

ggcaggagaa tcgcttgaac ccgggaggcg gaggttgcgg tgagccgaga tcgcaccact 59820

acactccagc ctgggcaaca gcctgggtga cacagtgaga ctccatctca aaaaatacaa 59880

aaaattagct gggtgtggtg gcctgcgcct gtagtcccag ctacccggga ggctgaggca 59940

ggagaatgga gtgaacctgg gaggaggagc ttgcagtgag ccgagatccc accactgcac 60000

tccagcctgg gcgacagagc aagactcttg tctcaaaaaa aagaaaaaaa aaggaaaaaa 60060

gaaccctgat aataaagaaa ccaaatgttc aactctcaaa gctcggacac tttaaagaaa 60120

taattaataa aggcagaagt taaagggagg atgataaagc aatttttttt gttggttttt 60180

ttgagatgga gtcttgctct gtcacccagg ctggagtgca gtgatgcgat cttggctcac 60240

tgcaacctct gcctcccggg ttcaagcaat tctcctgcct cagcctcctg agtagctggt 60300

actacaggtg cgcgccacct ggcccagcta atttttgtat ttttattaga gacggggttt 60360

caccatattt gttaggctgg tctcaaactc ctgatctcag gtaatctgcc cacctcggcc 60420

tctcaaagtg ctgggattac aggcaggcgc caccgcgcct ggcctaaagc aaaatattgg 60480

ttctgtgcaa aaggtcaata aaaagagcaa acgtttacaa actggagcca gcacccattc 60540

agctcagtgt gtctggagaa aaaacaatct cgcttcagaa ttcatgatta cgcagccctt 60600

tttgcttcct aaaaatccta ctatgttgct gttgaccatt ctctctcttt ctctctctct 60660

tgctttctct ccagaaaagc tattcagaca ttctcctctt tcctcaaacc tccaacactt 60720

cctcctccat ccttagcctc agctgctgac ctcacttcta atcattgaga aaccaggaga 60780

agcatttaag agtgaacctc cgcctccccg cacgggcaaa accacccacc cacagaattg 60840

tgccccaatt ctgcgtcctc tcctctcacc atggatggac ggtccaggct ccgagccaaa 60900

gccaggcctc ccctggagct ctggatccac cacctgcagc ttctcaggca gggccccagc 60960

agctcccctg ctcccttgta ccatcaatcc ctcccctcac tgggtcactc ccaacaatat 61020

atatatttag tgatgtttct cccatgtggt aaaatcactt agcctctctc ctcccccagc 61080

tactatccta tttgtttctt tccattctct gcaaaacttc tcaaagcatt gtgtctatgt 61140

gctgactcca tttatcttct cccgttctct gctgagtcct tcccacagac tctcacccca 61200

gttactccat gaaatgacct ctgcactgcc acatccaatg gtgaatgttc agttcttaat 61260

tttattcagt ctttcagcag catttgacct ggccgatcac tccctcttct taaaaatact 61320

tttctcagcc aggcgtgatg gctcacacct gtaatcccaa cactttggga ggccaaggcg 61380

ggaggatcat gagagcccag gagttcaaga tcagcctggg caacatggca agaccctatc 61440

tctacaaaaa ctaaaaagta gccagtgtga tggcatgcac ctgtagtccc atctacttag 61500

gaggctgagg cagtaggatg acttgagcct gggaaatcaa ggctgcagtg agccatgatt 61560

gcaccactgc actccagcct gagtgacagc gagaccctgt ctcaaaaaga caaaatagga 61620

aacttttctc agcatattcc tctgattctc ctgctgcttc tgtctgcaca gattcagtct 61680

cctttgccgg ttcttcctca tcctcctgat ctcttgacct tgaagtgccc cagagtacag 61740

tctttttttt tttttttgag acgcagtctc gtctgtcacc caagctggag tgcaatggcg 61800

aggtctcagc tcatgcaacc tctgcctcct gggttcaagc gattctcctg cctcagcctc 61860

ccaagtagcc aggactacag gcacatgcca ccatgcccag caaattgttg tatttttagt 61920

agagacaggg ttttactata ttggccacgc tggtctcaaa ctcctgaact cgtgaaccac 61980

ccgcctcggc ctcccaaagt gctgagatta caggcatgag ccaccacacc cggcccagag 62040

tacagtcttt agacggcctc tctacctata cttgctcccc tcataaactc ctcctgcctc 62100

atggctttaa ataccatcgg tagactgatg actcccatat ttctcttttt tttttggaga 62160

cggagtctcg ctcagtcccc caggctggag tgcagtggcg cgatctcggc tcactgcaag 62220

ctccacctgc caagttcaca ccattctcct acctcagcct ctccagtagc tgggactaca 62280

ggcacccgcc accacgcctg gctaattttt ttgtattttt agtagagatg gggtttcacc 62340

atgttagcca ggatggtctc gatctcctga cctcgtgatc cgcccatctc ggcctcccaa 62400

agtgctggga ttataggtgt gagccaccgt gcccagccga tgactcccat atttctatct 62460

cttgctgtgt gggagttctc ctcagaactc catactcata aatccaactc tcataaatag 62520

tatctcaaat gggcaatatg ctcaaaagtc aattcctact tttctcccta aacttgcttt 62580

cctgcagtct ccaccatctt aatgtccaat ctaacattag gaggcaaaaa ctttgaagtc 62640

attcttgact cttctctatt acacacccta tccaatcttt ctgcagatcc agtcgacccc 62700

caaatccagt tagctctcat catctcccct gttaccccct ggtccaggcc atcttcctct 62760

ctcacctgaa tcactgcagc attctcctca ctggtctctt tggttctgtt ttcactccac 62820

cttagcatag tctccacaga gcagtcagag ggatcctttt aaagtgtaat tcccatcctg 62880

tccctgctct gctcaaaacc ctgtcgtgat tcccgtttta atctgtcaga ttaaaagcca 62940

gagtctttcc agtgacctac atgatctgcc tattatcacc tcccacttct ttccccttgc 63000

tcactccact ccagctctgc agctgtcctt tctgtttcct gaacagccca gattttgctt 63060

ctttagaacc tttgtatttg ctgtcccctc tgtctggaat gtttttccag gaagtcacct 63120

ggctctctcc tgcacttcct tcctgaccac catgtttaaa aatcactcaa acacacttca 63180

ggccggacat ggtggctcac gcctgtaatc ccagcacttt gggaggccaa ggtgggtgga 63240

tcacctgagg tcaggagttc gagaccagcc tggccaacat ggtgaaactt cgtctctact 63300

acaaatacaa atagtagcca ggtgtagtgg cacacacctg taatctcagc tactcaggag 63360

gctgaggcag gagaatcgct tgaacccaga aggcagagga ggtgcagtga gccaagatca 63420

cgccacaaca ccccagcctg ggtgacagag caagacccca tctcaaaaaa aaaaaaagaa 63480

aaaaaaatca cacaaacaca cttctcttca tattcctttt ccaagtttta tttttctcca 63540

gaatacttta cattgtttta atggaagttc tccgtttccc cccaactaga atggatactt 63600

cctgcaggta ggcactctag tcctcccatc caagtactaa ccaggctcaa ccctgcttag 63660

cttctgagag caggggagat caggcctgtt cagggtggta tggcccagga attttgattc 63720

tgttttattc attgctgttc tgttgattct cttttgttcc tcctcctagt gctgagaaca 63780

ctacttgtac ataataagca ttcaataaat atttgttgaa tgaatgactt gttgaatgaa 63840

ttaatctcag aaatgcagga ctggttctac attagaaaat ttttcaaggt cattctctgt 63900

tgtcgtaaca cattaagaga ggaaaatttt gtactctaaa tcatttgata aaatacatac 63960

tgatttctgt tttcaaaaac tcttagtggc tgggcgaggt ggctcacatc tataatccca 64020

gcattttggg aggacgaggt gggcggatca cttgaggtca ggagtttgag accagcctgg 64080

ccatcatggt gaaaccctat ctctactgaa aatagaaaaa ttagccgggt gtggtggcgc 64140

atgcctgtag tcccagctac ctgggaggct gaggcaggag aatggcttga acccgggagg 64200

cggaggttgc agtgagccaa gatcatgcca ttgcactcca gcctgggtaa cagagtgaga 64260

ctccatctca aaagaaaact cttagtgagt ttaggaatcc aaggaagacc ctcaaactaa 64320

atagataatc tagctaccag aagccttcag taaaccttaa cactccatgg tgaaacatta 64380

gaaacattcc tactaaaaga caggctaaga atgcctgcaa tcttcacggc tagtccaaga 64440

agtcaaaaag aagaaatgag cgctgattta aaaaaataaa caaacaaaaa actaccgatg 64500

cagaggctgg cagcaaggac tgaaggactg tacagtactt gcctggagca ggcggatggc 64560

cacacccctg cgaagcctgc tcagctggct gggggacgct ccagtgtgtg agtggcagga 64620

tgcagggtac ttcctctgcc agggagttgc actggggaga tcctccccca ctcacacttt 64680

ggcagctggg gctttggaat gtgacttagc ttctgtcaaa gggtcaatcc accctttgat 64740

atatgatgca aaggcgaaca tatgatgcaa aggtgagaga acagcccaaa ttaggacttt 64800

taccacagct gtggaggtgg acagcgacag tggtgggccc tggccagact tttcatgctc 64860

aaaggtggtg gttgttcttc ctacttcttg tccctccagg gcttcctttg cctgtgtgct 64920

gaacctgctt cttttaattt tttttaactt ttttaaattt ttaattgttt taattaaaac 64980

aaattttgaa aactgtctga acctgctttt gaaccctgct atgatttgaa tgtttgtccc 65040

ctgccaaact gattttgaaa cttaatctcc aaagtggcaa tattgagatg gggctttaag 65100

cagtgactgg atcatgagag ctctgacctc atgagtggat taatggatta atgagttgtc 65160

atgggagtgg catcagtggc tttataagag gaagaattaa gacctgagct agcatggtcg 65220

ccccttcacc atttgatatc ttacactgcc taggggctct gcagagagtc cccaccaaca 65280

agaaggctct caccagatac agctcctcaa ccttgtactt ctcagcctct gtaactgtaa 65340

gaaataaatg ccttttcttt atgaattacc cagtttcaga tattctgtta taaacaatag 65400

aaaacgaact aaggcaaact ctcatgattc tactgccatg ccattccaat aaactccctt 65460

tatgcttaag agagccagag ttggccaggc gtggtgactc acgcctgtaa ttccagcact 65520

ttgggaggcc gaggcaggtg gatcacaagg tcaggagatc gagaccatcc tggctaacac 65580

ggtgaaaccc cgtctctact aaaaatacaa aaaaattagc tgggcgtggt agtgggtgcc 65640

tgtagtccca gctactcggg aggctgaagc aggaggagaa tggcgtggac ccaggaggcg 65700

gagcttgcag tgagtcgaga tcgtgccact gcactccagc ctgggtgaca gaatgagact 65760

ccgtctcaaa aaaaaagaga gccagagttt atttctgttg cttgcaacca agaaatctgg 65820

ctggtgcact gaagtttcca taaataatag caatttaaag actctttcca agccaggcaa 65880

tgcctagcct tgtgtagtcc ttgtggtaat acattcattc attcatttgt tcaaccaact 65940

gtgctccaga gactaagaat acaaaaatgg gggccgggtg tggtggctca cacctataat 66000

cctagcactt tgggaggccg aggcaggtag atcacctgag gtcaggagtt cgagaccaac 66060

ctggccaaaa tggtgaaacc cctactctac taaaaataca aaaaattagc tgggggtggt 66120

ggcggacacc tgtaatccca gctactcgtg agactgaggc aggagaatca cttgaacccg 66180

ggaggcagag gttgcagtga gccgagatcg caccactgca ctccagcctg ggcaacaaga 66240

gcgaaactcc acctcgaaaa aaaaaaaaaa aaaaaaagag ggccggggct gggcgcagtg 66300

gctcacgcct gtaatcccag cactctggga ggccaaggca ggagaattac gaggtcagca 66360

gatcgagacc agcctgacca acatggtgaa accccatctc tactaaaaat acaaaaatta 66420

tccgggcgtg gtggcgcaca cctctagtcc cagctacttg ggaggctgag gcaggagaat 66480

cgcttgaacc cgggaggcag aggttgcagt gagccgaaat catgccactg cactccagcc 66540

tgggtgacag agtgagactc cgtctcaaaa aaaaaataaa aaaaaaaaaa gaattcaaaa 66600

attgtagagt tatagtgtgc ttctagttta gttgagagga catctgtcct tcaaggaagg 66660

ctagaatcta taccctgagt ccttactgaa atcaatccag cagtcaaaac atgggaccaa 66720

cgatcacagc agtaagatag gaagagcacc tttgtacatt tagctcatgt tgagataagc 66780

cactgacaga gctgaaggaa gctcacagtt ctgggttcca tcctttggca tttaaaaaga 66840

aaagtgctaa gaaaattcgg ttggtcacgg tggctcacgc ctgtaatccc aacactttga 66900

gaggccaagg caggcagatc acgaggtcag gagttcgaaa ccagcctggc caacatggtg 66960

aaaccccgtc tctactaaaa acagaaaaat tagccgggca tggtggcgca tgcctataat 67020

cccagctact caggaggctg aggcaggaga attgcttgaa cccgggaggg ggaggttgca 67080

gcgagtgaga gcaggccact gcactccagc ctgggagaca gagcaagact ctgtctcaaa 67140

aaaaaaaaag aaaaaaagaa agaaaggaaa aaaagaaaga aaaaaaaaga aaaaagaaaa 67200

ttcaggccag gccaggcctg gtggctcaca cctgtaatcc caacactttg ggaggctgaa 67260

gcgagacggt gccttagccc aggagtttga gaccagcctg agcaacatag cgagaccctg 67320

tctctataaa aaaaaatttt tttttggcca gacgcagtgg ctcacgcctg taatcccagc 67380

actttgggag gccgaggcag gtggatcacg aggtcaggag atggagacca tcctggctaa 67440

cacggtgaaa ccccatctct actaaaaaat acaaaaaatt aaccgggcgt ggtggcgggc 67500

gcctgtagtc ccagctactc gggaggctga ggcaggagaa tggcgtgaac ccgggaggcg 67560

gagcttgcag tgagccgaga ttgcgccact gcactccaga ctgggagaga gtgagactcc 67620

gtctcaaaaa aaaaaaaaaa aaaaaaaaat taattgtcag gtgtgctggc atgcagctgt 67680

agtcctagct actcgggagg ctgaggtaag aagatcgctt gagcccagga gttcaaggct 67740

gcagtaatag tgcctctcac tctaccctgg gtgacaatga gaccctctct caaaaagaaa 67800

gaaaaaaggg aaagaagaaa agaaagaaag aaagagaaga aaggaaggaa gaaagaaaga 67860

aaaagaaaag gaaggaagga agaagaaaaa aaaagaaaga aagaaaagag agagaagttc 67920

aaagaccaaa gggtcaggat cccaaaatag tttttatgtt ttatttattt atttacttat 67980

ttatttttga gacagtatgg ctctgtcgcc caggctggag tgcagtgatg cgattgcggc 68040

tcactgcagc ctccaaactg ggctcaggtg gccctcccac ctcagcctcc cgagtagctg 68100

ggaccacagg cgcgtgccac catgcccagc taatttttta attctttgta gagatgaggt 68160

ctctatatgc tgcccaggct ggtctcgagc tcctgggctt aagccatcca cccgcctggg 68220

cctcccaaag tgctgggatt acagaagtga gccaccgcgc ctaatcgggt ggtttgtttg 68280

tttattgacg gggtctcgct gctgcccagg ctggagtgcc agtggctgtt cacaggtgca 68340

gtcctggagc attgcatcag ctcttgggct ctagcgatcc tccagagtag ctgcagctgg 68400

gattccaggc gcgccaccgc gcggggctca gaatgggttt ttatattgag ggttatgctg 68460

ccacctagag gatatatgta gtaccgaact gtgtgcgcag ggaggctgag gttgcagtga 68520

gccaagatga tgccagggca ctccagcgtg ggtgacagag caagatttca tctcaaaaaa 68580

aaaaaaaaaa aaaaaaaaaa aagaattgaa agtaaggtct tgaagagata tttgtgcctg 68640

tatggtcata gcagtattaa ctttgaccca ctagctaaaa cacaaaagca acatgtgtct 68700

gtcagcaggt gaacggataa acaaaatgtg gtatatatgt acaattgaat attattcagc 68760

ctttaaaaag gaataaaagg ctggatgcgg gggctcacgc ctgtaatcct aacactttgg 68820

gagactgagg tgggtggatc acccgaggtt aggagtttga gaacagcctg gccaacatgg 68880

tgaaacttca tctctactaa aaatactaaa attagccggg catggtggca cttgtctgta 68940

atccaagcta ctggggaggc taaggcagga gaattgcttg aactcaggag ccggaggttg 69000

cagtgagcta agatggcacc actgcactcc agcctgggca acagagtgag actccatctc 69060

aaaacaaaca aacaaaaaat tattatttcc aaagaaacaa gaccctgggt ccatttccca 69120

gcccacacct gatgttgact cacaacacac agcctggttt gctatgagcc tgcttcattt 69180

aattgtcacc ttaacttcac atcaccctca agtcctggaa taactctttg ctgacctttg 69240

tgtgctgagc catctccatg tcgctcaacg tgcagtccct ctcactgcac tgagtcaata 69300

gccagacgtg gtctgactgc agggtcatcc ttggtggctt aggctgactc gggcatagca 69360

gggtgctctg agacctcacc gcatataggc tttgccccca ataaactcta tataatattc 69420

atattatgtg gtctgggtgt gtgtagcttt gcactgtctt ctcgtgacag tgccctcaac 69480

ctctttccca ggatttcctc ctctacctcc tcaagtccca ctgctctgca aagaccaaaa 69540

gctgcagagt cccagctccc tcctttacac cccacgacgc agcctcctct ctcagaaccc 69600

tttaaacaga gtcttttact gcagatccca agaacagcca cacccctctc tcccacccac 69660

tccagacaca cccaggtaat tatagcaccc agggtaacta tgtagatgga gtccctggaa 69720

catgtggata gtgccccctg ggagtatgca aaagcaacat tgctggcacc tgcagagaac 69780

agggtgacat ccaggaatca gagcatgggc ctctgggagg tagggatgtg gccaggcagg 69840

ctgccaaaaa ttggtagagc aaggccacag gatctttctg accttccttc caaacagagg 69900

ctcctgtact ggtgatccct gtgttgattg accactccct tcctgggggt cgtggtctct 69960

gtcccagttg cccggacttc tgtgagtgtc ctactgaggt ccttttcatg agaagcatgc 70020

tgtccttcca cctgctggga gcaagagtga caacttcaat actataatag cagtggcata 70080

cagagaagaa gaaagatgaa gtggcaagaa aaacaggctt ccaagcagga gtttttctat 70140

aaaaacaaaa acgtttacaa gcaaactttt tataaagggc tagatagtaa atattttagg 70200

ctttgagagc cacatagact tgtttgcagg gactcaatgt cgctattgta gtttgaaagc 70260

agccatcagg gttatgtaaa tgagtgagtc tgattttgtt tcagcaaaat tttatttacc 70320

aaaacagaca atgagtgggc tggatttggc ccatgatcct tagtttgcca actcctgctt 70380

tgggctcacc cagatctgat tttgaattct ggctctgcta ctggttagct gcaggagctt 70440

ggaaggctct ctgagcctgt ttcctcatct gtaaaattaa agcaataatt tctaacactc 70500

aagagtgtta cctcacgcct gtaatcccag cactttggag gctgaggcag gcggatcacc 70560

tgaggtcaga agttcaagac cagcgtggcc aacgtggcaa aaccctgtct ctactaaaaa 70620

atacaaaaag tagccgggca tggtggcgcg catctgtaat cccagctact tgggaggctg 70680

aggcagggat actgctagaa cctgggaggt ggagcgtgca gtgagtggag atcacacctc 70740

cacactccag cctggccgac agagcgagac tccatctcaa aaaaaaaaaa aaaaagagtg 70800

ttagaaggtt ttgagataat gaataaaaga tgccttgtgt atactaagta ttcaacaact 70860

gatagctgca ttggtctaat tataacagtt tagaagcgat tgagtcaaca aatgctggat 70920

ttgtcaggga ggacttccta tcaggaggta gatcttgggc tgagtcctga agcaaagata 70980

ggcattggat agaggagttg agagaacacc ctaggactgt tattattatt attcgacacg 71040

gagtctcttg ctctgtcacc caggctggag tgcagtggcg cgatctcggc tcactgcaac 71100

ctctgcctcc caggttcaag cgattctcct gcctcctaag tagctgagac tacaggtgtg 71160

tgccaccaca cccggctaat ttttatattt ttagtagaga cagagtttca ccatgttggc 71220

catgctggtc tcgaactcct gacttcaggt gatccacccg cctcagcctc ccaaagtgct 71280

ggaataacag atgtgagcca ccgcacccag cccagaacca tttttcaatc cttggctctg 71340

ccttttatta gctgcaagat ctcaggcaat ttatttaacc tctccaaaga ctcattttct 71400

cattcacaaa atgaggcaaa taataatatc tactatccca ggttgtcatg agaattaaat 71460

gcaacatgac atttaatgaa atgagaagtc ccttggacat taactggcta aagtatgtgc 71520

tcgacaagga tatcatttta ggtggatact tagcatctca gaactgatgc tcacaatgga 71580

atatcattga aacgcattaa aattcatttt aaatgattgt aggtagtgag gcaattgaaa 71640

gaagaagaca agaggactga ttataatgct tcaggctcac tagtctcctt ttaggaggga 71700

aaaacaattt caagttaaat tttaggctct agatttttac ccctgctgct cattagaatc 71760

acccagattg atgaaatcag agcccatctg aggctgtgtt tttcatctcc agaatgagag 71820

ctgttgtggg gattaagttt ttgaaaaagt acatctaaca ggtgatcgaa aatgatagtg 71880

atattattgc agtgatggtc attattgttg ttattattat actgaaagag gcttcagttt 71940

tctgatccat aaagtgaggg aattgcatga gaccattgct aagattcctt ctagctctgt 72000

ttttttgttt ttgtttttta gacagagtct ctgtcgccca ggctggagtg caatggcatg 72060

atcttggctc actgcaacct ccgcctcccg ggttcaaatg atcctcctgt ctcagcctcc 72120

gaagtagctg ggactacagg cacacaccac catgcccagc taacttttat atttttaata 72180

gaggtggggt ttcaccatat tggtcaggct ggtctcaaac tcctgacctc aggtgatcca 72240

cccgcctcgg cctcccaaca tgctgggatt acaggcatga gccactgtgc ccaacccctt 72300

ctagctttct tgatcactga ttctagggtt ctctgctgaa atatatttga gacatcctgg 72360

ataaaagatc atgcaagagc tcccaatatg gtattaataa ttgattctgg aggcttagct 72420

actcctgatg gattagacat gactcaactg cctctcttat gtgtacaaca caacaacaca 72480

accaagaaag gttattctgg cattccattt attcagttta tttacagccc ttacttccag 72540

cagcacgtta aagatatggc cagggccggg tgcagtggct caagtctgta atcccaggac 72600

tttgggaggc caaggtgggc ggatcacaag gtcaggagtt tgagaatctg gcaattcttc 72660

agacttagaa gcaaccagct cgataacaca gtcttgtgtg ggctctccct ctgtccctcc 72720

ctcgcttccc tcatttctca tccctgcccc tgagactgtg caccttcaca tagccctgcc 72780

atgagacctt catctcaggc tttgctttct ggggtaactg aggctaaaca ctgagtggcc 72840

ctaaaagagg attgggattt ggaagttaga ttattcacca gagaacagac tttgctgatg 72900

atcaggccca ggttgtaatt gttgaaaaaa agagaggatg catagtctta tctcatctcc 72960

tagtcaaagt caacaccatg ataaataaga gtcaaatcct gagatgtgaa ttggggacat 73020

ttgagtggtt aaccctgaga agcttgcacc ttcagacccc tcaatacccc tgctccccag 73080

agaaggctgg acattgacct cagcacaggc aggagccctg caagatgcca tttgtcctac 73140

taaagatgga cccctccact ctgtttctag gtaaataacc aaagtcaagt ctccacacag 73200

cctgagcaag aaagtcagag cctgctacag gagaaaatac cacactggcc aaaggattca 73260

ctagccctgg ccactgtgtg tgggaggaac cagggaatca tgtgtgggag tcaatgttga 73320

agctgttgga ctgggggtgg ggtggaatat aagcctggcc ctggggagtt tttcccgttt 73380

gagggccttt acccacaact caagatccag tgctatagca ggagatccca gagctagtcc 73440

taacagatgg tcaggattga acttggccta gagtaaaatg aggaggatag tgccagaact 73500

ttctcaacat actattgagg aagaggtcag aaggcttaag gaggtagtgt aactggaaag 73560

gggtcctgat ccagacccca ggagagggtt cttggacctt gcataagaaa gagttcgaga 73620

cgagtccacc cagtaaagtg aaagcaattt tattaaagaa gaaacagaaa aatggctact 73680

ccatagagca gcgacatggg ctgcttaact gagtgttctt atgattattt cttgattcta 73740

tgctaaacaa agggtggatt atttgtgagg tttccaggaa aggggcaggg atttcccaga 73800

actgatggat ccccccactt ttagaccata tagagtaact tcctgacgtt gccatggcgt 73860

ttgtaaactg tcatggccct ggagggaatg tcttttagca tgttaatgta ttataatgtg 73920

tataatgagc agtgaggacg gccagaggtc gctttcatca ccatcttggt tttggtgggt 73980

tttggccggc ttctttatca catcctgttt tatgagcagg gtctttatga cctataactt 74040

ctcctgccga cctcctatct cctcctgtga ctaagaatgc agcctagcag gtctcagcct 74100

cattttacca tggagtcgct ctgattccaa tgcctctgac agcaggaatg ttggaattga 74160

attactatgc aagacctgag aagccattgg aggacacagc cttcattagg acactggcat 74220

ctgtgacagg ctgggtggtg gtaattgtct gttggccagt gtggactgtg ggagatgcta 74280

ctactgtaag atatgacaag gtttctcttc aaacaggctg atccgcttct tattctctaa 74340

ttccaagtac caccccccgc ctttcttctc cttttccttc tttctgattt tactacatgc 74400

ccaggcatgc tacggcccca gctcacattc ctttccttat ttaaaaatgg actggggctg 74460

ggcgcggtgg ctcatgcctg taatcccagc actttgggag gccgaggcgg gcggatcatg 74520

aggtcaggag atcgagacca tcctggctaa cacggtgaaa ccccgtctct actaaaaatg 74580

caaaaacatt agccaggcgt ggttgcaggt gcctgcagtc ccagcggctc aggaggctga 74640

ggcaggagaa tggcgtgaac ctgggaggtg gaggttgcaa tgagccgaga ttgtgccact 74700

gcactccagc ctgggtgaca gagcgagact ccgtctcaaa aaaaaaaaaa aaaaaaaaaa 74760

tagctgggca tggtggcgcg tgcctgtaat accagctact ctggaggctg aggcaagaga 74820

atcgcttgaa cccagtaggc ggaagttgca gtgagccgag atcttgacac tgcactccag 74880

cctggtgaca gagtgagact ctgtctcaaa aaaaaaaaaa agaaaaaaaa agacagaaag 74940

aaagagcaca gacagagtca caggtatttg cagtaggaag ctgtcaggtt agagtgcacg 75000

gaaatagaaa gtatatttta cacttacagc acatcttcgt ttgattagcc acatttaaaa 75060

tactgaatag caacgtgtgg ctatttagta ttcactaaaa tcttggacag tgcaagtcta 75120

aagaatcctt gatccgtccg gcatggtggc tcacgccttt aatcccagca ctttgggagg 75180

ccaaggtgga aggatcactt aaggtcagga gttcgagacc agcctggcca acatggtgaa 75240

acctcgtctc tactaataat acaaaaaaaa ttagccgggc atggtggtgc atgcctgtaa 75300

tcccaggtac ttgggaggct gaggcaggag aatagcttga atccaggagg cgctgcagtg 75360

agccgagatc atgccatgcc actactgcac tccagcctgg gcaacagagt gagactgtct 75420

caaaaaaaaa aaaaaaattg ttgggcgtgg tggctcacgc ctgtaatccc agcactttgg 75480

gaggctgagg ggggtggatc acctgggttc tggagttcga gaccagcctg gccaacatgg 75540

tgaaacccca tctctactaa aaatacaaaa attagctggg cgtggtggtg ggcacctgaa 75600

atctcagcta ctcaggaggc tgaggcagga gaatttcttg aacccaggag gcagaggttg 75660

cagtgagcca agatcgcgcc tctgcactcc atcctgggtg gcagagcaag actatgtctc 75720

aaaaaaaaaa aaaaaaatac ttgattgtct ggacattctg cagaacatca tatggagaca 75780

ctatgttgac gacatcatgc tgattgtaag caagaaatgg caagtgttcc agaaacacag 75840

tcaagacaca tacatgccag aaggtgagat ataaactcta ctaagattca gtggcctgcc 75900

acactggtga catttttaaa cctgctagat gtttgtgtag aaaaggattt aaccttgccc 75960

aaagaggggt ctggcctttg tccccagcta ctggacataa tctctttaaa ctcttgaaat 76020

atcattcctg atagaagtat ttttgttttg actaggggcc ttgggccagc cagatagcaa 76080

caatgtgatc tgggttgggg gctttggatc aggtggcatc agtgtgacct cctgagtggc 76140

tagagactag aatcaaccac atgggcagac aacccagctt acatgatgga attccaataa 76200

agactttgga cacaagggct tgggtaagct ttcctggttg gcaatgctct atactgggaa 76260

acccattctg actccatagg gagaggacaa ctggatattc tcatttggta cctccctggg 76320

ctttgcccta tgcatttttc ccttgtctga ttattattat tattatgaga tggaatctcg 76380

ctctgtcacc caggctggag tgcagtggaa tgatctcaac tcactgcaac ctctgcctcc 76440

ccggttcaag cgattttcct gtctcggcct cccgagtagc tgggactaca gatgcatacc 76500

accacacccg gctaattttt ttgtattttt agtagagacg gggtttcacg ttagccagga 76560

tggtctcgat ctcctgacct catgttccgc ctgcctcggc ctctcaaagt gctaggaata 76620

catgtgtgag ccaccgcgcc cagccccctt ggctgattat taaagtgtat ccttgagctg 76680

tagtaaatta taaccgtgaa tataacagct tttagtgagt tttgtgagca cttctagcaa 76740

attatcaaac ctaaggatag ccttggggac ccctgaactt gcagttggtg tcagaaataa 76800

gggtgctcat gtgtgtacca tgccctctaa ttttgtagtt aattaacttt cacaacttta 76860

ttattaccgc ttacactcaa tgtttattca catttatcca cataccactt attctagtgc 76920

cttgcatcaa agactttcta tctcatgtac tttattctgc ttgaagtaaa tcctttagga 76980

tattcttttt tttttttaaa ctttgcacat acatactttt attttttatt tatttttaat 77040

tttgttattt ttgtgggtac gtagtagata tatgtattta tggagtacat gagatgtttt 77100

gatacaggca tgcaatgtga aataagcaca tcatggagaa tggggtatcc atcctctcaa 77160

gcaatttatc cttcaagtta caaacaatcc aattacactc tttaagttat tttaaaatgt 77220

acatttaatt ttgtattgac tagagtcact ctgttgtgct atcaaatata attttttttt 77280

tttttgagac agagtctcac tcagtggccc agactgaaag tgcagtggca caagctcggc 77340

tcacttcaat ctctgcctcc ctggttcaag cgaatctcct gcctcagcct cccacatagc 77400

tgggattaca ggcacacacc accatgccca gctaattttt atattttttt agtagagacg 77460

ggttttcgcc atgttggcca ggctggtctt gaactcctgg cctcaaatga tctgaccacc 77520

tcagcctccc aaagtgctag gattacaggc atgagccacc acacctggcc aaaatagaat 77580

attctttagt gaggtctgct ggtgacaatt tttttctttt ttttgagact gagtctcgct 77640

gttgtcagct tgggctggag tgcaatagca cgatctcagc tcactgcaac ctccacctcc 77700

cggattccag caattctcct gcctcagcct cccaagtagc tgagagatta caggcaccca 77760

ccaccacacg cggctaattt ttgtattttt agtagaaatg ggggttcacc gtgttggcca 77820

ggctggtctc gaactcctga cctcaggtga tccacccacc ttggcctccc aaagtgctgg 77880

gattacaagc atgagccacc acgcacagcc aattttttcc gtttttgtct gaaatcttat 77940

tttgtgtcat ctttgaaata tatttttgat ggatataaaa ttgttggttg atagttatta 78000

tcattattat tattattttg agacagggtc tcactctgtt gcctatgctg gggtgtagta 78060

atgtgatctc ggttcactgc agacttgacc tcctagggct caggtgatct tcccacctca 78120

gcctccctag tagctgggac tacagatgca tgccaccata cccaactaat ttttctattt 78180

tttgtagaga tgaggctttg ccacatttcc caggctggtc tctaactcct gagctctagc 78240

aatccaccca ccttggcctt acaaagtgct gggccatgac tagccagcag ttacttttta 78300

tagcatattg aatatttaat atgaatcttc tggcatccac tgtaactgtt taaaaaatca 78360

gctgtttact tggcactctt tttttttttt ttttttttga gacagagtct tgccctgtcg 78420

cccaggctgg agtgcagtgg cgtgatcttg gctcactgca agctctgcct cccgggttca 78480

cgccattctc ctgcctcagc ctccggagta gctgggacta aaggcgcccg ccaccacgcc 78540

cggctgattt ttttgtattt ttcgtagagt tggggtttca ccgtgttagc caggatggtc 78600

tcgatctcct gacctcgtga tctgtccgcc tcggcctccc aaagtgctgg gattataggc 78660

gtgagccacc gcgcccagcc tctttttttt ttttttttag acggagtctt actctgtcat 78720

ctaggctggt gtacagtggc gtgatctcag ctcagtgcaa cctccacctc ctgcctcagc 78780

ctgccaaata gctgggatta caggtgcgta ccatcacgcc cggctaattt ttgtattttc 78840

agtagagatg gggtttcacc atgttagaca ggctggtctc gaactcctgg cctcaagtga 78900

tctgcctgcc ccagcctccc aaagattaca ggcatgagcc accgcacccg gccaagtagc 78960

actcctttga aggtaatctg cttcccctac ccctagcaat ttttaacaat ttttcttcat 79020

ttttatttcc tgaagttttg ttattaataa tctgtgtgca gatttctttg tatttctttt 79080

gtttgcagtt catagtgatt cttgaattag tgtgttggtt tctgttatca ccacaggaaa 79140

attgtcagcc gttagctttt caaatatttc cttgctaaat tctctcttct cccctttcgg 79200

tacaattgat ttgattaaaa ctaaaaccag ggccgggtgc agtgactcat gcctgtaatc 79260

ccaacacttt gagaggctga ggcaggtgga tcacctaagc tcaggagttc aagaccagcc 79320

tggccaatat ggtgaaaccc cgtctctact aaaaatacaa aaattaccag gcatggtggc 79380

acacatttgt agtcaggagg ctgaggcagg agaattgctt gaatccagga ggtggaggtt 79440

gcagtgagct gagatcccac cactgcagtc tggcctgggc gacagagtga gatgagaatc 79500

tgtctcgaaa aaaaaagtta tgaatgtttg ataaactata tttgttagaa tgtttgttgt 79560

agaatactat tcattgattt ttaaacaatg ttagattaaa ccattcactg gatttgtgat 79620

aattaactta ctgattttac ctcactgatt tgttgtaatt aatacaactg gtataaaaag 79680

actgtgacga ggccgggcat ggtggctccc gcctataatc ccagcacttt gggaggctga 79740

ggcaggcgga tcacctgagg tcaggagttc aagaccagcc tgaccaacat ggtgaaaccc 79800

catctttact aaaaatacaa aattagccgg tcgtggtggt gcatgcctgt aatcccagct 79860

cttcgggagg ctgtggcagg agaatcactt gaacccggga ggtggaggtt gcagtgagcc 79920

gatatcgcgc cattgcactc cagcctgggc aacaagagcg aaactccgtc taaaaaaaaa 79980

aaagaaaaaa aacacataaa acaaaacaac actgtgacgg ttcccaaaaa ttaggagcat 80040

aattaaagga actcctgata aaaattaatt ttatcttaca tgtaaactaa aatgacttta 80100

tgaagttaat tcagaaatac aatgcagggt attagtttgc cacagctgcg tattcagcct 80160

aatgtaatat tcttgttatt tttaaattct tcttttaact ttactcatat gtggatcatc 80220

aaatttcaaa agattaaatg acaatactct tagcagcaag cttccctaag catataaaca 80280

ttttaatggg tgatgattca gaaggtaccc gaagaatatg tactgccaga tatcattcac 80340

ccccatatac ctgcccgaca gacatcccat tttgggaccc tggataaatg tgtgggtgga 80400

gagaaagata ggagaaagtg gtataagcaa atggctttgg agtctgattg acagcgattg 80460

aaatcctgtc tctacctctt aacagcctca tgatcctaca taagttaccc cgatcctcag 80520

ggccacatct gtaaattggg ggttgcgatg gcagccatct cacagggtct cttttcgggg 80580

aagggcagga attatggatt aagtgagcta gtaattgtaa agcacttaat acaaggaggg 80640

cgcataataa gtacttcata aataatgacg gccattatca tgactgaggt gtatgcagct 80700

gtcggggatt acggcgactt cagaatttct ggtgggcagg gctcaaaggc agcaaatcac 80760

actggaagtc gaggtgaggc actgcttctg cacagactgc ttagctggag agaatgagga 80820

aggcttagag gagatttaga ggaacttaga gtcctccgcc tccaactctg tgggatctgc 80880

tcccgtgcca gagacattca ggggatttct cgcactctcc cctcccctac gtccctcccg 80940

ccccatccaa ctaaccacac aacacataca aaatagcccc tgcgaggttc tgcacgctgg 81000

aagggaacag gagaagggcg ctgcgctttc ttgctgatgc cctgtacttg ggcccctggt 81060

agacacagcc acttgtcccc tcagcctgca gagaaatccc acgtagaccg cgcccgggtc 81120

cttggcttca gccaatctcc ctttggtggg ggtgggatgc acgatccaag gttttattgg 81180

ctacagacag cggggtgtgg tccgccaaga acacagattg gctcccgagg gcatctcgga 81240

tccctggtgg ggcgccgctc agcctcccgg tgcaggcccg gccgaggcca ggaggaagcg 81300

gccagaccgc gtccattcgg cgccagctca ctccggacgt ccggagcctc tgccagcgct 81360

gcttccgtcc agtgcgcctg gacgcgctgt ccttaactgg agaaaggctt caccttgaaa 81420

tccaggcttc atccctagtt agcgtgtgac cttgagcagt tgactttatt tttcagtgcc 81480

tagttttcca gataccagga ctgactccaa ggactattac tcatctggag ggtttagcac 81540

agtaccgtcg catagtaaat ttccatgtca gttttggtta cctttcatgc acttgcaaac 81600

atgccatgct ctgaaacgaa ataggcacat cttttttttt ttttttttta aggagtcttc 81660

ctctcgccca ggctggagtg cagtggcgcg atcttggctc actgcaacct ccacctcccg 81720

tgttcgagat tctcctgcct cagcctcctg attagctggg actacaggca tgccacgacg 81780

cccagttaat ttttgtattt ttagtagaga cggggtttcg ccatcttggc caggctggtc 81840

taactcctga cctcaggtga tctgactgcc tcagcctctc aaagtgttgg gattacaggc 81900

ataagccact gcatctggcc agaaatgaaa taagtaaatc ttttaacctg ctctaacaat 81960

atagtgaaaa gaccatatta ttattagagc aggttaaggg atttgcctat ttcgggttct 82020

agttatagtc ttaaacttgg acattcttgt agaaagtaaa aagtttcctc ttcaaagttc 82080

cccttcttgt taaagaatac atcataagtg ttagaagtaa tagtttattt taaagactaa 82140

ctttcttcaa gcctccttgc tttgtgctaa taactctttg ttaagcccta tcctatgtaa 82200

ctgttggaca tgctcacagg cacgttccag ttcacagcct atgccccttc cttatttgga 82260

aatgttattg cttccttaaa cctttcggta agcaacttcc tctccttctt cgttcttcct 82320

tgcacttacc tatttagaaa gttttaggct attagcaaat cggctatcag tttaagagtg 82380

tgaggtcccg ctccagccaa tggatgcagg acatagcagt gaggacgacc caaatgcgta 82440

agggataaat atgtttgctt ttcctttgtt caggtgtgct ctcgacatcg ttccatctgc 82500

gattgagcac cctttctgca gaaagtaaag attgccttgc tggagatctt ttgtctccgt 82560

gctgactttt cttcgtggca ccgattatct atttctaaca attttggtat ttctaacatt 82620

ctgaacaatc ttgggctagt tgtctcttct gggcctgttt ccccatccgt cacatgataa 82680

acttcattgg tttaaaaacc ccagcgaaca tttattgagt tactattacc ttcctgccct 82740

ccccaacccc aaccccaggg agcagttaca acctcagccg ctgagcgcac tcgccgggtg 82800

ttaagaagca ccaaagacag ggaggcttga ttgattttgc tttgggagta gagggtcaga 82860

agattcacag gaaaatggca tttgagcaag gatgattcac tggagctagc ttttaaatac 82920

tggcgaggct tttatgttgc agtcccttac aaagttgagc attcgcaggg actgcactcc 82980

gaaataagcc cgcttcccct tttcattcgc taatgatcca gggagctgct ggttccgcat 83040

gcggcaggtt gtgccttttc ctaatcaggg ttctgcatcg cctcgaaccc gcaggccgtg 83100

gcgggttctc ctgaggaagc agggactggg gtgcagggtg aagctgctcg tgccggccag 83160

cgcctgtgag caaaactcaa acggaggagc aggaggggtc gagctggagc gtggcagggt 83220

tgaccctgcc ttttagaagg gcacaatttg aagggtaccc aggggccgga agccggggac 83280

ctaaggcccg ccccgttcca gctgctggga gggctcccgc cccagggagt tagttttgca 83340

gagactgggt ctgcagcgct ccaccggggg ccggcgacag acgccacaaa acagctgcag 83400

gaacggtggc tcgctccagg cacccagggc ccgggaaaga ggcgcgggta gcacgcgcgg 83460

gtcacgtggg cgatgcgggc gtgcgcccct gcacccgcgg gagggggatg gggaaaaggg 83520

gcggggccgg cgcttgacct cccgtgaagc ctagcgcggg gaaggaccgg aactccgggc 83580

gggcggcttg ttgataatat ggcggctgga gctgcctggg catcccgagg aggcggtggg 83640

gcccactccc ggaagaaggg tcccttttcg cgctagtgca gcggcccctc tggacccgga 83700

agtccgggcc ggttgctgaa tgaggggagc cgggccctcc ccgcgccagt ccccccgcac 83760

cctccgtccc gacccgggcc ccgccatgtc cttcttccgg cggaaaggta gctgaggggg 83820

cgccggcggg gagtcaggcc gggcctcagg ggcggcggtg gggcaggtgg gcctgcgagg 83880

gctttcccca aggcggcagc aaggccttca gcgagcctcg acctcggcgc agatgccccc 83940

tgagtgcctt gctctgctcc gggactcttc tgggagggag aaggtggcct tcttgcgcga 84000

ggtcagagga gtattgtcgc gctggttcag aagcgattgc taaagcccat agaagttcct 84060

gcctgtttgg ttaagaacag ttcttaggtg ggggttagtt tttttgtgtt tctttgagga 84120

ccgtggatca agatcaagga aatctcttta gaaccttatt atggaagtct gaagtttcca 84180

aatgttgagg gttttatgtc taaaagcaac acgtgaaaaa attgttttct tcacccagtg 84240

ctgtcttcca atttcctctt tggggggagg ggtagttact gctgttacta aaataaaatt 84300

acttattgct aaagttcccc aacaggaaga ccactacttt tgatgacttt ggcaagtttg 84360

ctaactactg gaaccctaac ttacaaacga actacttaca tttttgattt ccagttgtat 84420

tacctgccca atgtttacgt agaaacagct taattttgat tctgggtaac gttgttgcac 84480

ttcattaaaa atacatatcc gaagtgagca agtatgggtc tgtggacagc agtgattttt 84540

cctgtcaatt cctgttgctt cagataaaat gtaccagaca gaggccgggc gcggtggctc 84600

acgcctgtaa tcccagcact ttgggaggct tggcgggtgg atcacctgag atcgggagtt 84660

caagaccagc ctgaccaaca tggagaaacc ccgtgtctac taaaaataca aaattagcca 84720

gggtggtggc gcatgcctgt aatgccagct acttgggagg ctgaagcagg agaatcgctt 84780

gaacctggga ggcggaggtt gcggtgagcc gagatagcac cattgcactc cagcctgggc 84840

aaaaagagcg aaactccgtc tcaaaaaaaa agtaccagac agaaatgggt tttgttttct 84900

ttttttgttt tgagacggag tttcgctctt gttgcccagg ctcgagtgca atggcgcgat 84960

ctcagtctcg gctcactgca acctctgtct cccaggttta atcgattctc ctgcctcagc 85020

ctcccaagta gctgggatta cccatgcccc accatgcccg gctaattttt gtatttttag 85080

tagaaacggg gcttcaccat gttaggctgg tcttgaaccc ctgacctcaa gtgggcctcc 85140

cacctcggcc tcccaaagtg ccaggattac aggcatgagc caccgcggcc agccagaaat 85200

gggttttgga aaaagcacta aacaaaatcg aacttggttt catatgacag ctctgctgct 85260

aactgtaaca ggggcagacc agttaaccta cttttctgtc ttctgtcagc tgagaattag 85320

atgattccca aaggcccatt gaactctgaa tgactttaaa tacttcttct taagtgggta 85380

cacggttttg gtaactgatg ccaggtgatg aatgcatgaa agtgcttaat gaatgaaacc 85440

ggtaaaatag taggaggaag ctttattggt aaggcagggg tatacctaat agctctctaa 85500

tttattggta ttgaagtggt taacttttgt ttttttaagg ggggaaaaca ttctaagaat 85560

aatgaggcaa actgcatatt gcacaagaga ctgttgtctc tattcaacaa ataccttttg 85620

agtgtccaga gtctgccagg tgctgtgcta ggccctcacg attgagtagt gaaccagaga 85680

atgtccctgc acccatggag cttattgtct actggggtag acagataata aataagcaaa 85740

caaatcttct ctcttctccc tttcgctcca tgtaagtgtg tgtgtatagg tgtatactta 85800

caagttgagt aaagtgttat gaaagattaa gaggagaaat gcattttggt tagatgttag 85860

aggactcagc aggtgacctt gaaacttaga gctgaaggat cagtaggagg taactagaga 85920

ggccagggaa tcgcatgttc aaaggccagg aggcaagaaa gagcatggtg cccttcaaga 85980

gaggaaagaa ggctactgtg actggagcat agatgtaggc aagtgttggg tgattgagag 86040

ctctacgggc catggttagg ttttattcct aatgccgaga tgccaaacat ggtggttcat 86100

atctgtaatc ccagtatttt aggaggccga ggcaggaata tagcttgaac ccaggagttc 86160

aagaccagcc tgagcaacat gagacctgta caaaacattt aaaaaattgc tgggtatgat 86220

ggtgcacacc tgtggtccca gctactcagg aggctgaggc agaaggatca cttgagccta 86280

ggaggtggag gctacaatga gccatatttg agtcactaca ctccagcctg gatgacaaag 86340

tgagaccatg tgtcaaacaa aatacagaaa gaatattaat ttaaaatttt gaaagaggag 86400

tgatctgaac ttatatctta aaaagatcat tctagggcat ggtggctcat gcctgtaatc 86460

aagggctttg ggaggctgag acaggaggat cacctgaggc cagttcgaga tcaacctgta 86520

cagcatagag agactccatc tctacaaaaa gaaaaaataa atagctgggt gttgtgagtt 86580

attcaggagg ctgaagcaga aagatcactt gagcccagga gtttgaggct gcagtaagct 86640

atgatcccac cactgcaaca cagtgagatc ttgtctcaaa aaaaaaaaaa aatcattcta 86700

ggtgcttttt ggaggctgga tgtggtaaga gtagaagctg gagatggtcc tgttagggat 86760

tcgattcaga ctttaaatac catcaatgca ttgagtccca aatttacatc actacgttgg 86820

atccttgccc ctgaatccag actggtatat ccaactttag gttcagtttg tatctctacc 86880

tgaccaatat agaggtgtcc agtcttttgg cttccctagg ccacattgga agaagaattg 86940

tcttgagcca cacatagagt acactaacgc taacaatagc agatgagcta aaaaaaaatc 87000

gcaaaactta taatgtttta agaaagttta cgaatttgtg ttgggcacat tcagagccat 87060

cctgggccgc gggatggaca agcttaatcc agtagatacc ttcaacttac aatatctaaa 87120

attttatgcc agatttagtc attttaaacc tgctcatcag tttttctcaa gaagtagtat 87180

tttggctttt tttcttttct tttttttgag atggagtttc gctcttatcg ttcaagctgg 87240

agtgcagtgg cggatcttgg ctcactgcaa cctccgcctc ctgggttcaa gtgattctcc 87300

tgcctcagcc tcgcaagtag ctggaattac aggcatgcgc caccatgacc agctaatttt 87360

tggagacagg gtttcaccat gttggtcagg ctggttttgt actcctgacc tcaggtgatc 87420

tgcctgcctc ggcctcccaa aggctgggat tacaggcatg agccaccgct cccggctgca 87480

tttttggatt tttagttgct cagcccaaaa ctttagtaca tctttgaacc tcttctttcc 87540

tcctactcta tatctgatcc atcagcaaat ctgttaggtc tacctcacac atatcgaaat 87600

cctaccacgt ctcaccatct gtgacaatta acaccctggt ctaggcagtc atctctgtta 87660

agattgagtg gttaaggatg tcctctaagg agatgacatt caaatcttag cttaaatgtc 87720

aagagggagc tggttttata aagattgagg aggcagcatt attttgccat aggcttccat 87780

ttggtttcca ttccattctt gatacttatg gtatatattc aaaacaaatg cacagaaaca 87840

gacccaggta tattgggaat ttcggatata gagttcctag ttgggaaaag atagactgat 87900

ctgtaaatga tgctagttat ccatcatctg gcaaaaaata atttcctgcc tcctctcata 87960

tatctcagat caacagactt tttctgttaa gggccaaatc ataaatattt taggctttcc 88020

agaccatatg gtttctgtca cactctcctt tatccttgaa gccatagaca atatgtaaac 88080

aaatgggcat ggctgtgcta cgataaaact ttacttacaa aaactggtag tgggccagtt 88140

taggcatggc cagcactttg ggaggctaag gcagatggat cacttggggt caggagtttg 88200

agaccagcct ggccaacatg gtgaaaccct gtctctacta aaaatacaaa aaatagctgg 88260

gcatggtggt gggtgtctat aattccagct actctggagg ctaagacaca agaatcactt 88320

gaacccagga ggcagaggtt gcagtgagct gagatagcac cactgcactc cagccagggt 88380

gacggagtct taaagcaaaa caaaacaaaa ggtagtgggt tgtatttggc ccatgggctg 88440

tagtttgcca atccctgatg cagaaacaaa ttccaggtaa ataagagcct ggaatgttaa 88500

aaaaacaaaa cttgaagtca tgtagaagaa caggtagggg gaacaatcct gatctcagga 88560

taggaaggga tattgcttaa aataagacac aggaaaatat aatccatgtt gtgtaaattt 88620

gactacgtta aaacttaaaa ctttcgccaa gcgcggtggc tcacgcctgt aataccagta 88680

ctttgggagg ccgaggtgag cagatcacca ggtcaggaga ttgagaccat cctggctaac 88740

acggtgaaac cccgtctcta ctaaaaatac aaaacattag ccgggcgtgg tggcgggcgc 88800

ctgtagtccc agctacttgg gaggctgagg caggagaatg gcctgaaccc gggaggcgaa 88860

gcttgcagtg agctgagatc gcgccactgc actccagcct gggcgacaga gtgagattcc 88920

gtctcaaaaa aacaaaacaa aacaaagcaa aaaacctaaa actttcatac aataaagtat 88980

acctaagata cttctagaag agaagattta catccaggac gtgtatggaa tttctgcaag 89040

taataagtaa aagacaaggg acatgaagag gcagttcaca aaagaggaag ccaaaatgac 89100

caataaacat gaaaggatgt ttaacctcaa aggaaacaag gaaatgaatt aaaaacatca 89160

aatgccattt caaaactagt aagttggcaa aattaaaaat accaaggatg agaatatgaa 89220

gcatggctat atgagtgcat ggaatggtac agtcactttc attaaaaatg cacataattt 89280

gttttttatt tatttttttg agacagtcta tgtcgcccag gctagaatgc agtggcatga 89340

tctcggctca ccacaatctc tgcctcctgg gttcaagcaa ttctcctgcc tcagcctcct 89400

gagtagctgg gattacaggc acatgccaca acgcccggtt aagttttgta tttttagtag 89460

agacagggtt ttgccatgtt ggccaggctg gtctcgaact cctgacctca ggtgagctgc 89520

ttcccaaagt gctgggatta gaggcgtgag ccaatgctcc tggctgaaaa aaatgcacat 89580

aatttgttac ctagcaattc catgtctaga ggcttatcct agagaaattc ttgcttatat 89640

gcataggaag acgtgtacta gaatgttcac tagttgaatg tttaagtgaa aattaggaaa 89700

taaagtaaat gttcattaac aggaaaatga gtaaaggtat atttataaaa caattaagta 89760

gctaaaatga ataaactaga gctgcgtgaa tgaactagaa ctggttcaat agtcatgtca 89820

gattattgaa tgaatacagg tcagatatgt atagagtgtc atttgtgtaa ttaatttttt 89880

tttttttttt gagatggagt ctcactctgt tgcccaggct ggagtgcagt ggcgtgatct 89940

cagctcactg caacctccac ctcctgggtt aaagtgattc tcctgcctca gcctcccgag 90000

tagttgggat tacaggcatg caccaccatg cccagctcat tttcctattt ttagtggcca 90060

cagggtttca ccatgttggc caggctggtc ttgaactcct gacctcaagt gttccaccca 90120

acttggcctc ccaaagtgct aggattacag gcgtgagcca ccgtgctcag ccatttgcgt 90180

gatttttaaa gatgtgcaga ataatgccat taaaaaaaat acacatacat gtatatatat 90240

acacgtttgg ctgggtgtgg tggctcacac ctgtaatccc agcactttgg gaggctgagg 90300

caggaggatc acttgagccc aggtgtacaa gactagcctg ggcgagatag caagacccca 90360

tctcaacaac agaaaggata attaggtatg gtggcatgag aggatcactt gagcccagga 90420

gttcgagtgt tatcaggcca ctgcactcta gcctggacaa caaagcaaga ccgtgtctca 90480

aaaaaataaa aataaaaagt atttgtatgt ggtcatagtc aaaaaacgta catggaagga 90540

aaatgtcttt atttatttat ttattttttt ttttttaaga cagagtcttg ctctgtcacc 90600

caggctgggg tacagtggtg taatctcagc tcaccgcaat ctcggcctcc cgggttcaag 90660

cgattcttct gcctcagcct tctaagtagc tgggactaca ggtacccgcc accacaccct 90720

gctaattctt gtgttttcag tagagacagg gtttcaccat gttggcaagg ctggtctcga 90780

actcctgacc ttaagtgagc cacccgcctt ggcctcccaa agtcctggga ttacaggtgt 90840

gagccactgc gcttggccag gaaatatcta atttagtaag tatttatatc tgggaaagga 90900

agggtcaggt ggtgattcat aggaactcta aagtctatgt ataatactta gggggacaga 90960

aggaaataaa gcaaaatgct gatatttgat tgttgagttg tgtatatgtt agaagtataa 91020

cataggagat ctgattgata gtaggagaat gtttttaggt ggtaaaagtg gaaccgtggt 91080

ggtttgtttt ggcagtagaa tcagttggtc atagtttgta tgtggaaggt aataaacaga 91140

ccatgttaag gatgacttcc ggaattttgg tctgagtagt gggtggatga cagtgtcatt 91200

catgagggaa gatgaagact gaggtaggaa caggtttggg agaagatgac atgttccctt 91260

ttagacaagt ggaattatgg aagatggcag gtaggtggtt agctatatga atttgagata 91320

aaagatttag gatggagata taaatttagg agtaacagcg tatctatggt attgtaagcc 91380

ttaagaatgg gtaggatcag ccaggaaata cagatgtata tgcagaagag aggagtcaag 91440

gaagccaaga caagttaatg tttaaagtga gtgatgtagt ccatgggcag atgctgctga 91500

gagggctgca aacaccagtg accctacaac atttttaaat gtcgtcttcc tgacagcagt 91560

gatcagtacc tgcaacgatc ttatttattt ttttcatgtt agtctccaca cacttgaatg 91620

tagacttttt gaaggcaaaa tcattgcctt ttctgagctg ggagcatgtc tggcacatac 91680

caagcactca acagttgatg tattgacttc atccagatac tctgagggcg agttatttcc 91740

tgctactagc ctttcacctt tcaatgttta agagcacaaa tacagagatg ggcacgtttt 91800

ggcatttctt attttgataa ccttttcctg gtaagatttt ttaatgttga aaaaaaaaaa 91860

caagaaaaga gggttaaaaa tagtcttatg tcagatcctg tgatagaatt cacacttggc 91920

ttaagctgct gggcaccttc ctatcttgga tgtcatatta gcttatctac agcagaattt 91980

ttactgtttt atgtagtaag gaagcaatta tatgattatt ttacagacaa attattcttt 92040

atcttttatt tttttagacg gagtctctct ttgtctccca ggctggagta cagtgtcgcg 92100

atctcggctc actgcaacct ccgcctcctg ggttcaagca attctctgcc tcagcctccc 92160

aagtagctgg gcttacaggt gtccgccacc acacccagct cattgttttg tatttttagt 92220

agagatgggg tttcaccatg ttggccaggc tggtcttgag ctactgacct caggtgatcc 92280

acccgccttg gcatcccaaa gtgctggaat tacaggcgtg agccaccgtg cctggcccag 92340

acaaattatt atactctgag tgttagaggc ttaggatgtt ttcacttgat gctatgggag 92400

gaataagtaa taagatatga tacacaacca aagacctttc ttcactatgc ttctagtagc 92460

tagtactatg gatgacacat ggtaataata ttggttagca tttgtcctca atttactgtg 92520

ctagttactc ttctaagccc cttacaggta tatatttttt ttcatcaata atcctctaag 92580

gtagttttta ttattgacct aattttataa atcaagaaaa ttaagaccca gagaagtaag 92640

taacttgtcc aagatcacat ggcttataag tggtagagcc agaatttgac cccagatgtt 92700

gtgactacat tgtctctcca taagcaggtt caactctttt gactggatgc tgttccaagg 92760

tcacttcctt agagaagcct ttgctgacaa ctaccctcct gtgccctcct ccaaggctgt 92820

ccattgttct agaactttga atactcatct tagaataaag ctggtctaat ttttacagtg 92880

ttatagaatg gatctctgac tgcaaaagtt ggtcataatt atctttttat gttctagtga 92940

aaggcaaaga acaagagaag acctcagatg tgaagtccat taaaggtaag ttctgccctt 93000

ggcagtccac tgcattaaaa agtgatgtgc tttgcatttg tgagttcttt aatcctgtta 93060

tactctctct tttggcatta atcatttctg ccttatttta taattactta tgattttgat 93120

ttatttccct ctttaacctg tataatgctt taacatctag catataataa gtaggctttt 93180

tttttttttt tttttttgga gacggagtct tgctctgtta cccaggctgg agtgcagtgg 93240

cgcgatcttg gctcactgca agctctgtct cccgggttca caccattctc ctgcctcagc 93300

ctccccagca gctgggacta caggtgcacg gcgccacgcc tggctaattt tttgtatttt 93360

ttagtagaga cagagtttca ccatgttagc cagtatggtc tcgatctcct gaccttgtga 93420

tccgcccgcc tcggcctccc aaagtgctgg gattacaagc gtgagccacc gcacccggcc 93480

gtaagtaggc tttttttacc ttaattttat ttttttgaga tggagtcttg ctcttatccc 93540

caggctggag tgcagtggtg ccatctcggc tcactgcagc atccacctcc cgggttcaag 93600

cgattctcct gcctcagcct cccgagtagc tgggattaca ggtggccgcc accatgccca 93660

gctaattttt gtatttttag tagagacagg gtttcaccgt gttggccagg ccagtctcaa 93720

actcctgacc tcaagtgatc cactcgcctt ggcctcccaa agtcctggga ttacaggcgt 93780

gagccaccat gcctggccat aagtaggctt ttactgagcc ttgtgtgtat tggctatcct 93840

agtgattaca gtgaaccagt gcccttctta ttaatcacac atttaattgt tccctaaaag 93900

tgattagttc actttattta tttagtaaga caaaaaatga agaatactct taactgagca 93960

gtctgttaac tgtaggaaag cactgacact tataaggctt agttttctgt catttatcca 94020

gaagtatggt tgattacagt ttttactttt ttatttgaat gaacaacctt aatttaaaat 94080

atattttgtt tattttttgt tgggatcgat acattgtcct tgtttataga ttagagcatg 94140

ctttttaaag atgctgtatt actcactgat tttatttgtc cagtgtacag agattgaagt 94200

gggaaaatta taatggaaat tgtttccata gtcattacat attaatttca tcaatttatt 94260

tccataaaat ctgtagattg ctacttattt agatttttcc ttcaaatgtt tttatgttgt 94320

attgcttgca ctgagtattt attctatatg ctcaatttgc tggagaagaa gactaattat 94380

aacttaggca agttgtaaaa ttagggaaaa aagtaaggta ccttacagcc tagtttactt 94440

atttcttatg taaagccagt tagattccac attagttcaa actgccttct ttgagcaaaa 94500

cttgattggc agtgataaag gcttaaagcc cttctcaagc agagacctgt aaagactaga 94560

tctgactgta gtagaaggaa ggaacttaga tgtttcaggc agtgagaaca ccagtcttcc 94620

actctaaact ttgccactaa cagtatgacc ttgggaagtt gtaactttct tcagattctt 94680

catttgttga atggggggat tggcctagct aatttctaaa tctctactgg gctaaaaaat 94740

tctgtgctta tactctgatt atgaagtaca taatctgtgc ttaacattca ctgacttatc 94800

cttaggataa tacagaagca gtacaagaaa cagcccctca agatgtttgc agtctggtta 94860

gaaagacaaa cttatacaca gaacagtagc aaatagacca aaataataat agctgccatt 94920

tatagaacac ttcttctgtt ctgggcatta gacaaaaact gactataacg gtgaacaaaa 94980

aagacttagg tcctgccctc attgaactta cagattagta ggggagagga acattaatca 95040

agtaattcca cagatggctt agcctagatt ggtagtgatg gaagtaaaga gatgtgaacg 95100

gacttgaaaa aaaattcgga ggcaaaatgg atagaagttt attattgatt aaatatgagg 95160

tgtgagagag agggatattt aagattgata cctaccttct ggcttgccta acagaaccaa 95220

aacaggaaat tatatgttca gttttgttat gttgggtggg aggtgctttt gagtcattca 95280

tttatatatg ttatatatgt tattttatat gcatagtaat tttaaggtct gagttttaaa 95340

ccaaaggtta gagagtgatt ttttagagtc tagcaaacct aagttgaaat cctgcctgtt 95400

gaaatggctg tttactagct cattaaccta gggcaaagta ttcaacttgt tttcattttt 95460

gtcttcatct ctaaaatgag gaaaatatgg tcttacaaga ttgtcctgag agatagatga 95520

aataatatcc aaaaaaaaaa aaggtacata gagaaactcg tatagtgcct ggtatatagt 95580

aggtcctcca ttggtagcta tcattatcta gttttaacat agccttcagt ttgttgaatt 95640

agtcaaactg agtgaagcac tgcaaggaat tcagaggaat ttgagatcaa caaatgattt 95700

ctgaagttta gggaagactt catggcaatg acacttacct tgtataaaag ttgaagaata 95760

agaaagattt gaatgagaga ttctttctct tctccctacc agcccagctt cttatttgag 95820

gatatattgg gcaaaggggc cttcagacaa gtagagggag atttttacag aaagattgag 95880

atgaaggtat agaaggctgt aaagaccaga aaagagaatt gagacagagg aagcaggaag 95940

ccactgtagg tttttgagca agatattgat gctgtaagta tggtgtttat gaaaggttag 96000

tctggaagag atttgcagga tggagacccc ggaagttttt ttgttataat acagaaagac 96060

ttgcactgag ggtgaggtgt taaaaataaa caggtaagta aatgtttaaa catcttgaag 96120

gaaaagtcaa caaatcttgg caagtaaaca gataacagtg aaaaagaatg ggaccaagat 96180

tttgagtttt ggagactggt ggattgaaca gacagggaaa ttgagaggag aatcagatga 96240

tgatgtttta agttgatatt tagacagatt gtgcttgaga tggtaaagtc aatgtgggtg 96300

ggaatgctta gtagcgagta atcagtgata caagaccaaa gcccaggtca aagacaagtc 96360

acagatacag atcagggctt tttcatctgc tccacagagg tgtaccctag gagctgttgc 96420

aaacagtcca tgtggagggt gtgagtaaga tgtttccctt gaatttgcca gaattacttt 96480

tttgttgttg ttgttgtttt ttctgagaca gattctcgct ctgttgccca ggctggaggg 96540

cagtggcgag atcgcgcagc tcactgcaac ctctgcctct cgggttcgag tgattctcct 96600

gcctcagcct cccaagtagc tgggattaca ggcttgtgcc accaagccca gctaatttct 96660

tttgtatttt tagtagagat ggggtttcac catgttggcc agactggtct cgaactcctg 96720

gcctcgtgat ctgcctgcct cagcctccaa aagttctggg attacaggcg tgaaccactg 96780

cacccggtcc cttgttaagt ttattttggt gggaagcaaa ggaggtttca gcttttaaaa 96840

agtttgaaaa ttattgctct ggtaataatt aaagatttga gagtaaatat gctttctagc 96900

agaaagaata aaagaagaac agatagcctc aagaagggga gccaaagaag caggctatat 96960

ctgacacact gggtgttgat aaatgggtat taaaagaatg agagcaatga gcagatagaa 97020

gaggaaatta ggagagtata ataccatgga gaccaagaaa gatagactat caggaaggag 97080

tggtaaaaat aagttactag ttctaagaga gatgttaaga gggaccgggg aaagccttgt 97140

acaaatgagt tagtagcatt ttacattata tacatctaat taagaaacaa tgcgagagtc 97200

tcaccattcc tatagactct tacttgtact tgtctgaaca cgaaaactgg cttttgttta 97260

taaataagct aaaaattatt ttgctccaat ttctcatgaa aataaaaata aaccttcttt 97320

taacattgaa aaaatagttt gaagacagtc actcttcatt ttgtaattcc cacaactatt 97380

attgaatgac tgaaattatc tttattctga agccaaaggg gtgatactga tatttcttca 97440

gactactaaa aatatatttt atgaattttt agtgtgcttt atcttttttt gttttttttt 97500

ttgagatgga gtttcactcc cgttgctcag gctggagggc agtggtgcaa tctcagctca 97560

ctgcaacctt cgcctcccag attcaagcaa ttctcctgcc tcggtctccc aagtagctgg 97620

gattacaggc acctgccccc acacccagct aattttttgt atttttagta gagacagggt 97680

ttcaccatgt tggtcaggct ggtcttgaac tcctgacctc aggtgatcca cccaccttgg 97740

cctcccaaag tactgcgatt gcaggcatga gccaccatgc ctggcctgag gaatattttt 97800

ctaggttccc cccaccccaa gcatttattc tgcaatttta gttttgttcc taaagcaagc 97860

aaggtttaag gatttaaaaa taatccgtat tttagaatgc tttctggctt tgttactttt 97920

tatccacagt agaagttctc agagaatgat ctccctcttt taatttaact ttttggcaca 97980

gtattttgag aattataaat aatattagaa tgttttctgg ctgggtgtgg tggctcatgc 98040

ctgtaatcct ggctacttgg gaggctgagg caggagaatc acttgaacat gggaggcaga 98100

ggttgcagtg agccgaggtc atgccactgc actccagcct gggtgacaga gcaagactct 98160

gtctgggaaa aaaaaaaaaa aaaaaaagag tgttttcttt cctattttcc accacttgat 98220

taagttactt ttcctcttaa gtattttttg ctgagtatgc tgacttaaga gtaatgttac 98280

aaaatttaat ttttaaagtt ctctgaaagc ccctttatga gagttttagg ctatcaaatt 98340

gtgtttaatt cttaacaatt ttttgaaaaa ttatagcttc aatatccgta cattccccac 98400

aaaaaagcac taaaaatcat gccttgctgg aggctgcagg accaagtcat gttgcaatca 98460

atgccatttc tgccaacatg gactcctttt caagtagcag gacagccaca cttaagaagc 98520

agccaagcca catggaggcc gctcattttg gtgacctggg taagtaacta tcatttttta 98580

ttaacttgta ttagaaggat ttgagtacaa tatgtgaaac ttctgtcata ggatacagaa 98640

ctatataatt ggaaagtgct ttggaaaaaa tgtatttaaa ataacagcta caagtataat 98700

gggtagctgt gttgtgttcc tgtaaatata gaatataaag catgcccagt agaaaaacaa 98760

gcatttccag aagaaatata tctgatcact aaatataaat atatgaaaaa gatgtctcac 98820

tttattactg agggaagtgc aaattaaaat aatcagttaa tgttctccta acacattagc 98880

atatttttta aagtttgaca atttgaatgt cagtgaagat gcagggaaat acccctccta 98940

tttagtgata atataatctg gtgaagactc tttggaaagc aatttggaaa tcagtataaa 99000

atatgcatgt catttaggcc actctttcta agacctagcc ctcagatatg ctcattcata 99060

tgtgcaggtg tgtatgtgtg tgtgtgtgtg tgtgtgtgtg tgtatatgta tgtatgtatg 99120

tatgtatgta tgtatgttga aggctattca ttatagtatt gtttgtgata gcaaaaaatt 99180

atggacaaca tataaatatc tgttataggg aaataaccaa attgtggtat acgcatgctc 99240

tggagtataa tatagccatt tgtttctatt tatttatttt cttgagacag ggttttactc 99300

tgttgcccag gctggagtgc agtggtatga tcatggttca ctgcagcctt cacctcctgg 99360

gcacaagcca ttctctcgcc tcagcctcca gagttactag gactgcaggc atgtgtcacc 99420

acacccagat aattttttaa ttttttgtag agacagggtc tcactatgtt gcctaagctg 99480

gtctcaaact cctggcctca agcaattctc ccacacaggc ctcccaaagt gctgggatta 99540

ccaacgtgaa ccaccacacc tggttcagtg tagccattta gaaatctaaa aaagacgtgg 99600

gaaaatgtct aaggcatgtt taaatgtgag aaaagcaagt cacagtatgc atggtaaaat 99660

ccgttatatt aaaataagtt cttccaaaac aaaaacatat gcaggagacc tttattttgt 99720

cagtatttct tacccaaatt tctgcactta gaaaattgca tgtcatgttg tcataagttg 99780

aaaaaaagat ccatgaacca atggacttct aataaaatca gtcctgcttt tgacatctct 99840

ctctactttt gtgtatattc aaaccagagt gtcaatgtgt ttgtggggca cacttagcaa 99900

taatacatag cagacaaaat gcatatagct cagagagtaa aattgtaagt tttgctagat 99960

cactcataaa ttgctgatga gaatttaaaa tggtgcagat gctctggaaa acaggcagtt 100020

tctttctttc tttttttttt tctttttgag acagggtctc actctgttgc gcaggctgga 100080

gtacagtggc gtgattacaa ctcactgcag cctcaccctc ctcaggttca ggtgatcctc 100140

cctcagtctc ctgagtagct gggactatag gcatgcacca ccacgcctgg ctaatttttg 100200

tatttttttt tttttttttt gtagagacgg ggtttcgcca tgtttcccag gctggtctca 100260

aactcctgga atcaagcgat ccacttgcgt aggcctccca aagtgctggg attacgggcg 100320

tgagctactg tgcctggcct aggcagtttg tttgtttgtt tgtttgtttg tttatttatt 100380

tgtagacgga gtctcacagg ctggagtgca gtggcccaat ttttggctca ctgcaacctc 100440

cgcctcccag gttcaagcta ttctcctgcc tcagcctcct gagtagctgg gatgacaggt 100500

gcctgccata atgcctggct gatttttgta tatttagtag atatggggtt tcaccatgtt 100560

ggtcaggctg gttttgaact cctgacctca ggtgatcagc ccgcctcggc ctcccaaagt 100620

gctgggatta caggcatgag ccgtcatccc tggctggtgg tttcttatga cgtgaaacat 100680

gcaattacca tatgacctag cagttgcact ctgtatttat cccagataaa tgaaaactta 100740

ccttccaata aaaacctgtg cacaaatgtt catagcagct taatattgaa aaactggatg 100800

ttcttcagca ggtgaatgaa ctggttcatt cataccatgg aataccattc agcaataaaa 100860

aggaacaaac tgttgataca tttaaccacc tggatgaata tcaagggaat tatgctgtca 100920

gacaaaaacc agtccctaaa gactacatat agtatgattc cgtttggata atattcttga 100980

aatagagaaa ttaagagaaa tgaaaagatt agtgtttgcc agatgttaga gacagggagg 101040

tgagaggggt aagtgggtgt agttataaaa gtgcaacatg agggatcttt gtgatgttga 101100

agttgtatct tggcagtgga tgcagaaatc tcaatgtgat aaaattacaa agaactaaaa 101160

acaagaatga gtatagataa aactggggaa atctgaacaa gttagagtgt tgtatcactg 101220

tcagtatctt agagtgatat tgtactatag ctttgcaaga tgttaccatg ggagaaacta 101280

aagtgtacaa gggatctcta ggtattatta tttttttaga gatggggttt cactatgttc 101340

cccaggccgg tcttgaactc ctgggctcta gtgatccgcc tgccccagcc tcctaaagta 101400

ctggaattac aggcgtgagc gaccatgcct ggccctttca gtattgtatc ttagaacttc 101460

atgtgaatct agcattatct catagaattt aattaaaaga aattgtaaac ctcacagaag 101520

atcagaattt cctcaagttt gtgatgttga caaagatgaa ctagttgaca ctgacagtaa 101580

gactgaggat gaagacacga cgtgcttcaa aaaaatgatt tgaatatcaa tggattaaga 101640

agaactcttt tgacaaattg atgaaaccct cagtcagttt tataagaatg cccatcttta 101700

tgatcatgct atgaaagcca atttttaaaa aaattttttg tctttcctaa caattagctt 101760

gtggttataa tttaaattta gttaaatata agataaatga ttttttatta agtttagttt 101820

catttttcaa ggtacgatct caaagctact ctttaaccta ctatgaatga ataatgctga 101880

gttcataaca tctttgtaga tatatccaca attttccctc aggataagtg cctacaagtg 101940

gaattactgg actgaaaata atgcagtttg ctaagacttt gctatctgtt cctgaatgct 102000

cctccaaaaa ggttttgcca gtttacatcc tcatgaccag cgaatgagag tgttgcctat 102060

tttcctgtgc ccttgttact gcttaataat ttttgaaaaa aatctaattt gacagacaaa 102120

aatgcatttt atgttaattt gcttttctgg gatttttaat gaggttgagt atagttttta 102180

atatttttat tggccccttt ggaactagta tcataagttt tttttcttaa gaatttatgt 102240

agtctgggct gggcgcagtg gctcacgcct gcaatcccag cactttggga ggccgaggtg 102300

ggtggattgc cgaaggtcag gagtttgaga ccatcctgac caacatggtg aaaccgaatc 102360

tctactaaaa gtacaaaaac tagctcagcg tggtggcggg tgcctgtaat cccagctact 102420

taggaggctg agtcaagaga atcgcttgaa cccgggaggt ggaggttggt tgcattgagc 102480

cgagatcgcg ccattgctct ccagcctagg caacaagagt gaaaagtctc aaaaaaaaaa 102540

aaaaaaaaaa aaaaaagaat ttacatggtc tgaattgcca ttaaaagaga tatgagaatt 102600

attgagtaac aaataacttt ttaataattt aggcaagttt tggacgattg tactttgttt 102660

agaaaccaaa agcatagtat ttgtagtttt tttatttact ttagttgcta ggaagtaaac 102720

tttattcaag gtctctggta ccagttgttg ctaaaagtga ttgactaatc tgtcaatctg 102780

aaattatttg ttgctgaact gctaattctt ttgcttctat cttttaggca gatcttgtct 102840

ggactaccag actcaagaga ccaaatcaag cctttctaag acccttgaac aagtcttgca 102900

cgacactatt gtcctccctt acttcattca attcatggaa cttcggcgaa tggagcattt 102960

ggtgaaattt tggttagagg ctgaaagttt tcattcaaca acttggtcgc gaataagagc 103020

acacagtcta aacacagtga agcagagctc actggctgag cctgtctctc catctaaaaa 103080

gcatgaaact acagcgtctt ttttaactga ttctcttgat aagagattgg aggattctgg 103140

ctcagcacag ttgtttatga ctcattcaga aggaattgac ctgaataata gaactaacag 103200

cactcagaat cacttgctgc tttcccagga atgtgacagt gcccattctc tccgtcttga 103260

aatggccaga gcaggaactc accaagtttc catggaaacc caagaatctt cctctacact 103320

tacagtagcc agtagaaata gtcccgcttc tccactaaaa gaattgtcag gaaaactaat 103380

gaaaagtgag tatgtgattt tcttgtgtgt acatatgtgt ctcactttct ttttttaatt 103440

tactaagcag aacttcagat gaggaataaa atgattggaa tatttttttt ctcctctaac 103500

tacttgtaaa tttgggagaa tttggagagt gtagtagagt cagatcagtg tatggaaaag 103560

gagcaggagt gactggacct tctaagaagt gtgttatcag aattagtaaa tgaagggtca 103620

aatgtcctac ttttcccctc cactgatttt gacatcaaac cattatccac atagccttat 103680

ttcctccctc ggtcttaatt ttattaatat tttactgcac tttgcagata aaatttttaa 103740

aaaattttta aaaattgcca ataagtgaca tttattaagt tcagtgctta gtgtatattt 103800

ggattttatt tattagtcac aagacctttg tgcaggtagt aggcatgatt atcttttttt 103860

ttttgagatg gagtcttgct ctgtcgccca ggctggagtg caatggcgcg gtctcggctc 103920

actgcaacct ccgggttcat gccattctcc tgcctcagcc tcccaaatag ctgggactac 103980

aggcgcctgc caccacaccc ggctaatttt tttgtatttt tagtagagac ggggtttcac 104040

catgttcgcc aggatggtct cgatctcctg actttgtgat ccgcctgcct cggcctccca 104100

aagtgctggg attacaggca tgagccaccg cgcccggact gattatctta tttacacatg 104160

agaaaaccag ggcttagaaa ggttaggtaa cttcctctag gttgtacagt aaatgtggac 104220

ctagaagcat tttgacaaga gcacctgttt ttttttcttc tctattagtt tagaaattat 104280

atactcttaa ttatcacctg ggattttgat tagacagcct tcatgttctt tttcatctta 104340

aatgttcttt gtgtcttaaa gggctaagtg atttcttcag atcttttagt tcactcattc 104400

tcagtgaact aaaatgaggt ctaatctgct actgaatcaa gttttcagca tgttatttcc 104460

ttcctccctc cctccctcct tccttccctc aaccaggctc ccgaggagct gggattacag 104520

gcgcccgcca ccactcctgg ctaattttta tattttagta gagacggggt ttcaccatgt 104580

tggtcaggct gatcttgaac tcctgacctc aagtgaccca cctgcctcgg cctcccaaag 104640

tgctgggatt acaggcatga atcaccacac ctgacggcat gttattttca tcgcaaagtt 104700

actgtaagct gggagaagtg gcacacactt gtactcccag ctactcagga agcttaaggt 104760

gagaagattg cttgagccca ggagttttga gaccaacctg ggcaacacag caagacccca 104820

gctcaaacaa agaaaaaaag ttattgaatt ttttatttct atggatcatt ttttgtagtt 104880

tcttattcct ttcacccttc attcccactt ttgatcccat cttttattta tttagtttta 104940

ttaaatgtat atttgtctga taattctgct atctacagtt ttttgtggac ctgactcagc 105000

atttctttgt ttcttcggat tcagactgtt ggtggcttgt gattttagtg atttttggcc 105060

gtgaacatgt ttcttggact tttgtctgtg ggaattctct gtgtactctg tataaattaa 105120

gttacttcag gtgttttgca ttttcttttg ccatgcacct ggggcctggg tcactaccct 105180

tctggtacca cttaaaactg aatttttgtc ttgggtgctc gtactgatcc tgtatgagta 105240

caggtttata cttactgtag aaatatggtg tttgattatg gggtattgtc ccagatggtg 105300

ctggagtatt aatatgctct ctgttaaact taatgtgttg tccctgtaaa actccaaaat 105360

tctgaattcc agaatactac tggccccaaa tgtttaagat aagggcactg cctgtatttg 105420

tttctgcctc ccactatttt ccttagttta acacaaactc acctttttaa aaaacatttt 105480

gagagaattc agtattggga agagtttcta acctgtttct ggaaatggaa gtccaaagtc 105540

tgtttctgta attgtttttt ttttgagatg gagtctcact ctgtcaccca ggctggagtg 105600

caatgacgta ctctcagctc actgcaacct ccacctcccg ggttcaagcg attctcttgc 105660

ctcagccccc tgagtagctg ggattacagg tgcccaccac catgcctggc tgatttttgt 105720

atttttagaa gagatggggt ttcgccatgt tggccaggct ggtcttgaac tcctgacttt 105780

gtgatctgcc cacctcagcc tcccaaagtg ctaggattat gtttctgtaa ttgtaataca 105840

tttattgttt ttagaaactg tctttgcttt agtggtaatt ttcaataaaa atagaaatag 105900

cagtggagtt attaaaagag cattagttac atttttccct ttttcattat cttcaaatat 105960

tatatatagt aagtttgacc tttttaaaat gtatacttgt atcagtttta acacatacat 106020

agattcctgt aactgtcacc actataaggg taaagaacag ttagttcctt cacctttgaa 106080

gtcaagcccc acctctatcc caacacttgg caaccgctga tctttctccg tctcaatagc 106140

tttgcctttt ctcttttttt ttcttatttt tttttttgag acagcgtctt gctctgtcgc 106200

ccgagctgga gtgcagtgag gcaatctcgg ctcactgcaa cctccgcctc ctgggttcaa 106260

gcagttctcc tgccttagcc tccctagtag ctgggattat aggcacgcac caccacaccc 106320

ggctgatttt tttgtatttt tagtagaaat ggggtttcac catgttggcc aggctggtct 106380

caaactcttg acctcaagtg atccacctgc ctcggcctcc caaagtgctg ggattacagg 106440

cgtgagccac tgtgcccaat caggactttt tttttttaaa tttacattca acttgtcatt 106500

tttttcttgt atggattgtg ccttcagagt cacacctaag agccctttgc ctaagcaaag 106560

gtcatgaaga ttttctcata tgtttccttt taaaagtatt gtggttggcc aggtgccatg 106620

gcttatgcct gtaatctcag cactttgaga agctgaggtg ggcagattac gaggtcagga 106680

gatcgagacc atcctggcta atgcggtgaa accccatctc tactaaaaat acaaaaaaaa 106740

aaaaaaatta gccgggcgtg gtggcgggca cctgtagtcc cagctacttg agaggttgag 106800

gcaggagaat agtgtgaacc cgggaggtgg agcttgcagt gagccgagat cgcgccactg 106860

cactccagcc tgggcaacac agtgagactc catctcaaaa aaaaaaaaaa agtattatgg 106920

ttttacactt tacgtttaga tatatatctt ttttgagtta atgtcgtata agtatgaggg 106980

ttacgtcaga ttttttgttt tttgtttatt tttacatatg gatgtctagt tgttctaata 107040

ccatttgttg aaaagacaac ctttactcca ttgaattgcc tttgtacttt tgccatattt 107100

gtctaggcct gtttttggac tcctttttct gtttcatgat gtgtgtgtct attcctttgt 107160

taataccaca tggtcttaat tactgtatag taagtcttaa aattgggtaa tgctggcctt 107220

ataaaacgaa ttgggaagtt tttattttta ctcttatttc cattttctag aagagattgt 107280

gtagaattgg tgtcatttct tctttagata tttggttgaa ttgggaagtg atgccatctg 107340

ggcctagggt tttgtttttt gtgtgtgaga cagagtctca cttctgtcac ccaggttgga 107400

gtgcagtggt gagatcttgg cttactgcaa cctctgcctc ccaggttcaa gttatcctcc 107460

tgcctcagcc tcccaaatag ctgggattac aagcgtgtgc caccatgccc gactaatttt 107520

tgtattttta atgcagacag ggtttcacca tgttagccaa gctggtctcg aacttgtgac 107580

ctcaagtgat tagcccacct tggcctccca aagtgttagg attatagatg tgagccaccg 107640

tgcctggcag gggcctaggg ttttcttttt cagagtattt taaactatga attcagatta 107700

tttaatagat ataggactat ttaagttatc tgtttcttct tgagtgaatt tttactgtag 107760

tttatggcct ttgagtaatt aattgtattg aattgtcaaa tttatgagcg tgtaattatt 107820

tatagcattt cgggtttgta gtggtatccc tcttttattc ctggtgttgg caattgtgtc 107880

ttgtttttct ttgtcagatt gtatagggat ttattagtct tttcaaagaa ctagcttttg 107940

ttttgatttt tctgttgttt tgttttcaat tttattgatt ttctgctctt tattatttct 108000

tttctattat ttctgcttgc tttgggttta ttttactctt ttttttttct ccaagttgct 108060

taaagtagaa acttagattt ctggtttgag acctttcttt tctaagataa gcatttaata 108120

ctgtaaattt ccttctaacc actgctttag ttacaccccc acaaattctg gtattttgaa 108180

ctgagcacaa atgaaatgtt ctaatttccc ttgaatctta ttcttttacc aatgaattat 108240

ttagaaatat gttatttagt ttgcaagcaa ttggagactt ttttcctgtt atttttctac 108300

catttatttc tcatttcatt atattatggt cagagaatat attttgaatg atttcattta 108360

ttaattttta aaaataacat taaaaaattt tttaaaatgt gaatatacca catacagtat 108420

aaagattgta cattctgttt ttggacagtt ttctataaat gtcaagttga tttagttggt 108480

taatgatggt gttcagtttt tctttattct tgctgatact ttgtatgcag ttatatcact 108540

ttattactca gaagagtgtt gaactttcca actacaattt ttttttccaa ttttactttc 108600

agctctatct ggttttgctt catgtatttt gaggctctgt tgttaggtgt gtacacattc 108660

aggatgatat cttctgggtg aattgcctgt tttatcatta tgtaattccc tctttatggt 108720

aattttcctt gttctaagat cagaaatatc tgttgtccaa tttatataga cactgcagct 108780

ttcatttgat tagtgcttgc atggcatatc tttttccatt tttttacttt tgatctacct 108840

ttataattct atttaaaggg ggcttcttgt aggcagcata tagttgggta gtgttattta 108900

tttatttatt tatttattta tttatttatt tattgagaca gagttttgct cttgttgccc 108960

aagctggagt gcagtggtgc aatcctggct taccacaacc tccacctcct gggttgcagt 109020

gattctcctg cctcagcctc ccaagtagct gggattacag gcacgcgcac catgcctggc 109080

tgattttttg tatttttagt agaaacggat tttcaccatg ttagccaggc tcgtcttgaa 109140

ctcctgacct caggtgatcc acctgctttg gcctcccaaa gtgctgggat tacaggcgtg 109200

agccactgca cccggctgag tcatgttatt tttaatcttt tctcacaata cagggttttt 109260

gttggtaaat ttaattattt taatataaat tttagtataa ttatttacat taaatgtaac 109320

tgttgcactg gggtatttat aatgtgtaaa tataattatt ggtattaata taattatatt 109380

actcataata atattaatat ctttggattt agattaccag tttagtatat gtttttctgt 109440

ttctccctct ttgatttccc cttttttgct tttttttttt ttttaattct tatttttttt 109500

tagtatttgt tgatcattct tgggtgtttc ttggagaggg ggatttggca gggtcatagg 109560

acaatagttg agggaaggtc agcagataaa catgtgaaca aggtctctgg ttttcctaga 109620

cagaggaccc tgcggccttc tgcagtgttt gtgtccctgg gtacttgaga ttagggagtg 109680

gtgatgactc ttaacgagca tgctgccttc aagcatctgt ttaacaaagc acatcttgca 109740

ccacccttaa tccatttaac cctgagtggt aatagcacat gtttcagaga gcagggggtt 109800

gggggtaagg ttatagatta acagcatccc aaggcagaag aatttttctt agtacagaac 109860

aaaatggagt ctcccatgtc tacttctttc tacacagaca cagtaacaat ctgatctctc 109920

tttcttttcc ccacatttcc cccttttcta ttcgacaaaa ctgccatcgt catcatggcc 109980

cgttctcaat gagctgttgg gtacacctcc cagacggggt ggcagctggg cagaggggct 110040

cctcacttcc cagatggggc agccgggcag aggcgccccc cacctcccag acggggcagt 110100

ggccgggcgg aggcgccccc cacctccctc ccggatgggg cggctggccg ggcgggggct 110160

gaccccccac ctccctcccg gacggggcgg ctggccgggc gggggctgac cccccacctc 110220

cctcccagat ggggcggctg gccgggcggg ggctgccccc cacctccctc ccggacgggg 110280

cggctgccgg gctgaggggc tcctcacttc gcagaccggg cggctgccgg gcggaggggc 110340

tcctcacttc tcagacgggg cggccgggca gagacgctcc tcacctccca gatggggtgg 110400

cggtcgggca gagacactcc tcagttccca gacggggtcg cggccgggca gaggcgctcc 110460

tcccatccca gacggggcgg cggggcagag gtggtcccca catctcagac gatgggctgc 110520

cgggcagaga cactcctcac ttcctagacg ggatggcagc cgggaagagg tgctcctcac 110580

ttcccagacg gggcggccgg tcagaggggc tcctcacatc ccagacgatg ggcggctagg 110640

cagagacgct cctcacttcc cggacggggt ggcggccggg cagaggctgc aatctcggca 110700

ctttgggagg ccaaggcagg cggctgggaa gtggaggttg tagggagctg agatcacgcc 110760

actgcactcc agcctgggca acattgagca ttgagtgagc gagactccgt ctgcaatcct 110820

ggcacctcgg gaggccgagg caggcagatc actcgcggtc aggagctgga gaccagcccg 110880

gccaacacag cgaaaccccg tctccaccaa aaaatgcaaa aaccagtcag gtgtggcggc 110940

gtgcgcctgc aatcccaggc actctgcagg ctgaggcagg agaatcaggc agggaggttg 111000

cagtgagccg agatggcggc agtacagtcc agcctcggct ttcacaactt tggtggcatc 111060

agagggagac cggggagagg gagagggaga cgagggagag cccctttttt gctttctttt 111120

ggattatttg aatttttcct taaatttatt tatcttactt atttatttat ttttttgagt 111180

gattctcctg ccacagctcc caagtagctg ggactgcagg catgtgccac tacacccagc 111240

taattttttt gtatttttag tagagacagg gtttcaccat attggccagg ctggtcttga 111300

actcttgacc tcaagtgatc cacctgcctc ggcctcccaa agtgctggga ttacaggcgt 111360

gagccaccat gccctgcctt tttctagaat ttatatattg agttcttgat tgtatctttt 111420

tatgtaggct ttttagtggc ttctctagga attacaatat acatactttt cacagtgtac 111480

tcacatttaa tattttgtaa cttcaagtgg aatgtagaaa acttaaccac cataaaaata 111540

gaactaggga tgaggttaaa aaagagagag aaaagaaatg taataaagat ttaataacac 111600

cgtttttttt tttttttctc tttttttttt gagacagagt ctctctttct gttaccaggc 111660

tggagtgcag tggcgtgatc ttggctcact gcaacctccg cctcctgggt tcaagtgttt 111720

ctcctgcctc agcctactga gtagctggga ttacaggtgc gcgccaccat gcccagctaa 111780

tttttgtatt tttagtagag acggtttcac tgtgttggcc aggatggtct cgatttcttg 111840

accttgtgat tcgctctcct cagcctccca aagtgctggg attacaggcg tgagccaccg 111900

cgcccggcta agtctttaaa tatttttttg acattgcact ttttctcttt tccttctagg 111960

attttagtaa cccaaatgtt agttttgtta ttgtttggca ggttcctgag gctttcctta 112020

cttctttaaa tttttttttc ctgttgttca gcttcgaaaa tttctattca tctgtcttca 112080

aattcactgg ttctttcccg ttatttccat tctgttattg agtctttgta gtgaatttta 112140

aattttgttt attatgtttt ttagttctaa aattttcttt ttttgtgtat gtcttatact 112200

ttgctcctga aactcttatt tgtttcagga gtgatcttat ttcttagagc atggttttag 112260

tagctactta aaatttgttt tatcatccca gcatatgtgt cctcttgatt gtcttttctc 112320

ttgtgagata atgggatttt ctggttcttt atatgacaat taattttgga ttgtatcttg 112380

gacagtttga cttacgttac atgattctga atcttgttta aatcctgtgg aaaatattga 112440

agtttttgct ttaacaagca gttgacctag ttaggttcag tccacaaatt ctaagcagca 112500

ttctgtcggc tctggttcca tcatcagttc agttttgtat cttatctgct tatgtgcctt 112560

tctgtgtcca gtctgggacc tggccaatgg tcaggtccca aagcctttgt acacttttag 112620

aagcagggcc atgcacaccc agctcacgag tggccccggg agtgcacata caactcgacg 112680

ttttcatggg ctccttcttt tctgtgatgt ccctgacacg ttctgccttc taagaacctc 112740

cctttatccc tttcctgttg tctggctaga aagtcagggc tttagattcc ctatacttca 112800

gcacacttcc tgtagctatg tcaacctctg tggccacgac ttcttcttct tgggactgca 112860

gtttctcttg tcagaaagta ggattcttgg agctgctgtc attgctgctg tggctgctct 112920

gatgctgcct gggagtcgaa ggagagaaag gaacaaaaca aaacaaccca ggggatttcc 112980

tccactctct ttgatccgtg agagccccct ttcctgttcc tcagaccaga aatagagggc 113040

ctgtcttgga acttcttctt tgtgcatctg gtgtgcagtt tcagcttttg agtccaggcc 113100

aggaggtgct ggacaaactt gtcaggagta cggaggtact gcaagttctg attacttttc 113160

tcagtccacc tgcttccaag tccttggatg catttgtcca ttgttttgag ttgcattcca 113220

tgggagagac agaagagtgt gcttatttca tcttgacata cttattagga tttcatatca 113280

aatcaacgga tgatattctc tatattaatt tgctgttttc cctttagcaa gcacattagg 113340

aaaataacac tttaacaccc gcctttggtg gtttctgtca taattattaa tacttgactt 113400

tttttttttt tttgagacgg agtctcactc tgtcctttga ggcattgtcc ccataaactt 113460

ttggtaaagc atcaataatt ttatctttca tccacacaag cttcaccata aatttgatgt 113520

ttattcttcc attttagcag aattcatgtt gctccaatag gggctgtctt caaactgatg 113580

ttttctcctt cttagtgcct cagagtagat cctgttcaga tacgttataa caggttaata 113640

tgagtttatt ttggtgtaaa agtactttga aattcatgca tagttttttc atcatatgca 113700

ttttccatag ctttgaacac ccccatgtaa ctctcctctt ccacaaacca aacaatgaaa 113760

aagcaccttt gtgatggaag tttattttgc aataggaact cacagtgatc taagccctgc 113820

tattcatgaa tataattcat tactggagtc caagttgctt tttggttttt gaagttctct 113880

tcttcccttg caggtataga acaagatgca gtgaatactt ttaccaaata tatatctcca 113940

gatgctgcta aaccaatacc aattacagaa gcaatgagaa atgacatcat aggtaagcag 114000

tgcttgaaac tatggcaaaa aaaaaatgac aaaaaatgca cagaactgac aattttcgtt 114060

attgactaag ataatttttt cttaacatgg aatttagcag ttcccttcct aatttgtttt 114120

ctgagtattt tttatatcgg attatagctc actttaaaag tttctcggct gcattcggtg 114180

cgagggtctt tgcctgggcc agatgggctg cagtgtagcg ggtgctcagg cctgcccgct 114240

gctgagcagc cgggccggcg ggcggctacg ctaaccggca cagaccaccg gatggactgg 114300

ccggcagccc cgcaccagtg cacgaagtgg gcgggacaga aacttctggg gttggaagtc 114360

cagtgaggct aaaagccggt accaaagtct ctaggcatca gggctgcagc ccaagagtct 114420

cacgaccagt gggcaactgg atggccagac aggtgtctca gtggtggcct ctccgtctca 114480

gggcttcatc ccacttctca gtgggcctga cgtccctggg caccctggat gtctacctgc 114540

attagccaga gccatcacat ggcctgtgac ttgccttttt ttgccagttg attgtgccac 114600

acacagtgtc atttctgtgt catttggcac agctggaggt gcaaggagga gggcagcctc 114660

atgtccagtc ccagtttcac gtaactttat tcttctgaat aaagacaatt tgctaacctt 114720

aaaaaaaaaa aaaaaaaaaa agtttttctt atatgttgga cccaaattct taggctttaa 114780

cctgaataac aatgacagca agatcaataa atagtacaca tttattaaac actcactgtg 114840

tcccagacaa tattccaagc actttttatg gatagactca ttttaacttc taaagaactt 114900

tgtgggataa atacagttat tttatagatg aagaaactga agcacagaga agttaagtgc 114960

tttgtccagg gtaacagctc agatatggca gagtcaggat ttgaaactag accctcacat 115020

accttaactg ctgtgctgtg gcagtgtttt tcatactgta ggttgggacc agccttctct 115080

tatgccctca ccccctgcca aaaaaaaaaa aaaaaaaaaa aaatatatat atatatatat 115140

atatatatat atatatatat aatatatata tatataaaat atatatatat ataaaatata 115200

tgtattagta tatatgcata tatagtatat attatatatt agtatatata ctaatatata 115260

atatacatat tagtgtgtgt atatatatat atactagaat aaaaaaatca aagtatctca 115320

gagtagtaag gacaaacatt tcagaaaaat gttttcatta tatatacatg tatgtatgtg 115380

tatgctgatt caacaaatat atttcttata ggttatagca aaatagtttg aaagctttta 115440

ctgtgtttta tcaggaagac cttaggtgaa cgtatattca cagataaaag aggttattta 115500

ttcattcaat aaatattaca ttctcataag tcctaatatt atgtattttt attcttcaaa 115560

aaagttagta tttgtgattt atgaaataag acatgttctt gcacttttag cagatctgtc 115620

ccgatgttgg gcttctttaa tccttagtgt gggtgctttg cactcactca ctgctgggga 115680

cagcaagacc cctgttagtc tcagctgtgt ttcttaaatt ggcccactgt accttccagt 115740

tagctattct ggggtccatg tcatgttggc tccattttcc ttttctttct cccacacaga 115800

tacctataac ggctataaca taggcctggt ggctgttggt ggcttatccc tatctgcttg 115860

tatttaaggg gtactgtttc actgagtttt gctgacagat gttgtcatga gatttgaggt 115920

tttctgtgtt gttgctctat ttttatgtgg gaatttgcta ctatcatcat ccctagacca 115980

gcttttccta gtaatacaac agggatgttc tgactgatta gagtttgcct gtttgaagaa 116040

ttggttggct agtgattttt ttttgagggg agtctgtacc agttaatagc ctgactggcg 116100

tgtggataaa aaggaagcag tttcaagtca aataaaacac ttaaaatgaa accacactgc 116160

aactctcttt cttttactta agcttaatca aattaatgat gatgtaatcc catgaaggaa 116220

aagtcttctg aaggatcaag ttgataacat tttgtgatca aagaatttga gaaaacctct 116280

atcccagtgt ctatcattat atattttagg atgttaatta cctgtgtggc tttaggcaag 116340

tcatttttcc tccttgagcc ccattcttaa tcctgtccaa attatttgtc tcctcttgca 116400

gttggactat tttaatatag ctgtccttca agtgagtttt gttcaaagga gccttcactt 116460

tagctcttac tgtgtaccca ctttgcatag tcttgtttta aatgtaatcc ttggattttt 116520

ggtgttgcta actaattact gtttttatgt gaggatttag agtgatccag aatctatact 116580

tgcactacct ccttcatctt ccacaaatgt ttgaagtggt agaattttta aaaactttga 116640

aggtacagct gacagaattt gctgatggtt tggaagtgag tggtatgaga gggaaaaaaa 116700

ggaataaagc atgactgcat tttttgtttg tttgtttgtt tgtttttgag acggagtctc 116760

actctcgcca ggctggagtg cagtggcgtg atcttggctc acggcaacct ccgcctcctg 116820

ggttcaagcg attcccctgc ctcagcctcc caagtagctg ggactacagg cgctcgccac 116880

cacgcctggc taattttttt ttttgtattt tagtagaaac ggggtttcac cgtgttggcc 116940

aggatggtct ccatctcctg acctcatgat ctactcacct tggcctccca aagtgctgag 117000

gttacaggca tatatataag catataaagt gtgttatagc atacaaacag gtatatatat 117060

aaacatgcag tccacacagc tgataggaat gaggcagtag tgaaggagaa gttgatgtag 117120

gagaggggac agttgttaca ggaaagaagt ctggaggcag aagggatgaa ttccagtgct 117180

cacatagaag attgcttaga tgggagcaag gacaatttat ctagagtcac aggaaagaat 117240

gcagtacacg ggtagagatg caggtgagtt gaaagatgtg agagatgatg gaaataattt 117300

tctgattgct tctatattct caaggaagca ggaagcaaag tcctcagcaa agagaataga 117360

agaggtgtta aatatttgag aaaggagatg tactgtagaa aaaaaaaaaa ctcagtttct 117420

ccttctgaac tctcacaaaa cagaaccctt ccatgactct agttgtgtgg ggttttttcc 117480

ctgtcagcta ccaattctgc agatgattgt tcagtgaaca ccaactgggt gtcctctaag 117540

tcagttcagt tctcacactg tttacctgga gatagcatca gatcccacag attgaggact 117600

ctgtcccaca agactgcctc cacttcagat gccagtctca agtacaagtt gtggcctgtg 117660

cttctgactg accttctata aattggagtt cccacagtcc cctccttggg ttcaataaat 117720

ttgctagagc agctctcaga actcagggaa atgctttaca tatatttacc catttattat 117780

aaaggatatt acaaaggata cagattgaac aggcagatgg aagagatgca tgggcaaggt 117840

atgggagagg ggcacagagc ttccatgcac tctccaggtc atgccaccct ccaagaacct 117900

ctacagattt agctattcag aagcccccct ccccattctg tccttttggg ttttttgtgg 117960

agacttcatt atataggcat gattgatcat tggctattgg tgatcagctc aaccttcagc 118020

cccctcatcc cgggaggttg gtgggtaggg ctgaaagtcc caaacgtgta attctgcctt 118080

ggtctttctg gtgattagcc ctcatcctaa agctctttag aggccacagc cacaagtcat 118140

ctcattagcc ttcaaaagaa tccagagatt ccatgaattt taggcgctgt atgctaagaa 118200

actggctaaa ggccagttgc aatgtctcag gcctgtaatc ccagcacttt gggaggctga 118260

ggcaggagga tcgtttcagg ccatgagatc aaaaccagcc tggtcaacat agtgagaccc 118320

ccttacaaaa aatttaaaaa ttggccaggc gtaatagctc ttgtctgtag tctcagctac 118380

tcagaaggct gaggatcact gagccctgga gttgaaggca gcagtgagcc atgatcgtgc 118440

cactgactcc ggcttgggtg acaaagtgag accttgtctc agaagaaaaa ggaaaaaaaa 118500

aaaactgggc aaagactaaa taacatattt cacagtatca cagatttgta ttgtctagga 118560

aagtgaatgt aaacagacca ggacactagt atgatccctt ggtttcatga aggtcccact 118620

aaagtcatga acacaaagtg agactaggca tcatgttata tggtttttcc agccatgttt 118680

aacagctagc taaatagcta attgtttcgc tgcagtttat tttagcagtt ccttatttta 118740

gcacatttca tgttttaaaa tttctaccaa taacatttta ataaactttt ttacagataa 118800

cttcacaaat ccataatttt ttaagttaca atcccagaaa tagaattgct cattgaaagg 118860

gtatgttcat ttttaaagtt atgctagaaa ctgccaaatt gccttcagaa aaaggtgttt 118920

gtatccccac taacactagt gttagttttc ttgtgccctt gctcaagtat acatattatt 118980

aaaaacaatg ttgggccagt ttactagata aaaggtgtag tgcctcctta ttctaatcta 119040

tttgattact agtgagtatg tatgtctttt cacgttggtc attttatgtt tgttcctttg 119100

tggattgtca tgtcctttgc tcatttttct tttggaacat ttcttagtag tttataagag 119160

ctcttggtat tttaatgata gtaacctttt aactgtcatg catgctgcaa atcttttttc 119220

tgtttgtttg cctttgtatt ttgtttttgg agggtttcta tgtataggaa ttaaatttta 119280

tgttgttaaa tcttttgatt tctgcttttg catatgtact tcaaaagact ttctatttta 119340

agatcaagtg ttacctgtat tttcttttag ttctatttaa aacctcttaa tttatatgcc 119400

tgtgctgtta actcccaagt tgattcacaa gtgtgtatac atagtttgaa tttagtggca 119460

atttaattat ttacaacttc ttttgcagca aggatttgtg gagaagatgg acaggtggat 119520

cccaactgtt tcgttttggc acagtccata gtctttagtg caatggagca agagtaagtt 119580

agttcatatt ttcacattgt gcatcctagg gaatttgggt tcattgttag gaatgggctt 119640

cactcagcta aaaacaaagt atttttgaga atttaaatat tttggatatt tacaagatca 119700

tataaagcat actctatctt ggttaacagt ttcttttaaa tataaattat gtgaactctt 119760

aaaattttca ttttcatttt caatgttaat atttcctaag ttaaaataat ttgtttttag 119820

ttctgaaata atttggggag tgattgagtc tgtagtgatt atgactatta gaattggttt 119880

atttatttaa ataatgcatg tcttcagatg gctctcctaa tttgttagtt aggctttaag 119940

ctaaatggat gctatataac taaatccaca tagatttgtt gaaatggctc cagaggtttt 120000

ttagatttat tactgctatg tgcccttaaa aaaaatctat tcattctttc acttaacatt 120060

tatcagaaga gtgctctgtg taagacgtgg ttaggcatag tgccagtctt gaaggaagtt 120120

acagcctaat aaaagacata gggcatgttg tttggttact gtaatatgaa gtggcatgtg 120180

ttaaatgtca ggggagaact acaaagtcat aaaaaggtgg gagagattac atacaggtaa 120240

aggaatcagg aatgacacca tggggagtaa ggtagtgttg acctaggcct ttaagataca 120300

atagggacag tatggaaaga gtatattttt cccacttaaa ctctttcctt ggtcgttccc 120360

tcaaattttc ccttttgtcc atgtgcaggc actttagtga gtttctgcga agtcaccatt 120420

tctgtaaata ccagattgaa gtgctgacca gtggaactgt ttacctggct gacattctct 120480

tctgtgagtc agccctcttt tatttctctg aggtaaagtc tgcatttctt ttcacactct 120540

attcgagcat tccagcctct aactatcaat gctggggccc tgtctatagg aaataacaca 120600

gaagagccaa gtcatttcca aaaagatgta tcattgtttc aagttgtttc tgatggcaag 120660

agtaatttaa taatatatta gagagaacat gaaaattcaa tgtattaaat aactctaatt 120720

ttgagaaacc taattaaact actgcatgta agagagtgca tgtttttaat tatttggagc 120780

tattttaaaa ccacagaatt tgaaacttgc ttccagtgca taaattgcag accagacttc 120840

agaagagaaa aaaagtagta aattttttct tatgctcatc atttttactt tagtcacttg 120900

ataggattgc ccagtgaaga agcatttgca acagacaatg agtatattaa tctttttgag 120960

gcatacagtt tagtataatg ctctttgtta ggcttcaaca agtgaaatta ttttgttgga 121020

aagcaaatga ctattaagta gaaagaggat tcccagtctc acaaagcagt aatttagaca 121080

ctcgattctg cctctttaca agaatacagg tactcagttg atttgttttc tcactccctt 121140

tctttgctat aagtttaaat caacaatttg tttaggttaa tatgtcctca tggaatggtg 121200

gaaatgatca gatataaaat atttggtttg gttagtttac tctttatatg tttgctggca 121260

aggaaccaca aatccagttt agtataattt ttactctagt tcactaaaag tttgcatcca 121320

gctgtgtagg tagtgtttgt ttcttgttaa cttttttttc gtctaaaaga atactttaaa 121380

acttttcaat ctcaaatgac tgtaacttgc tgacaggtgt taacagaaga agtagatctt 121440

tttgtttttt gcttatgacc tgtattttaa tatttgagct tatagattag agattgtgag 121500

agaaatctgt ttatagtctt attttccctt gtgtattttt tcttcctagt acatggaaaa 121560

agaggatgca gtgaatatct tacaattctg gttggcagca gataacttcc agtctcagct 121620

tgctgccaaa aagggccaat atgatggaca ggaggcacag aatgatgcca tgattttata 121680

tgacaagtga gttatattga tagatggatt cagcagatac ttattgaaca tttgatatgt 121740

tttgtggaaa taaagatgaa taaactcagt ctctgttgtc aaggagctca caggaggcag 121800

cataaaagct gcttttatat ggtgtttgta aagctttggg ggttcttaga acaaaagttt 121860

ctgctgggaa aggggaggtg tatgtggggt aaacaggatg gcaatggtgg tgttcaagga 121920

gtgtttccca gaagagagat tttgtttgga tcccaaagaa agaagggaat tttgctaccc 121980

agagaaggca gaaaacaaca ttctaggcaa aggcattggc ccagaagcca tggaaacgta 122040

ggggaaagtg gcactttcaa gaaacttgag tttagataat caaaggagtg gggaataaat 122100

atgaggatgc tggtactaat tggaatagat tgtaagggac cttgaatgcc tatttatggg 122160

tatattatac tttctgtata aatctgctca ggcacgttgt taattagttt tttattagtt 122220

ttcactgaaa atgagaggat ggaaacatca tacagtaaac aaaattgaaa atatctggtc 122280

aggcagatga tgagcttgtg gccagctctg taacgtatgg tattcttttc atttaacttt 122340

tcttactctg taaaaaaagt aattcgtggt cgggcacggt ggctcactcc tgtaatcaca 122400

acactttgag aggcagaggc aggtgaatcg cttgagccca ggaatttgag accagcctgg 122460

gcaacatggc aaaacccgcc tttactaaaa atacaaaaat tagctgagcg tgatggcgtg 122520

cgcctgttgt cctagctact taggggcctg aggcagaagg atcacctgag ccttgggagg 122580

tcgaggctgc agtgagctgt gatccactgt actccaccct gggcagggca gtagagtgag 122640

accctgtctc caaaaaaaaa aaaaacaaca aaggtaattt gttatttgta tccttaagca 122700

aatgctaaag gggtaacttg gggatagaga aaagtccaca gatgttaggg tttgaagaca 122760

ctaatagtat ctaggccagt ggttcctgaa cattagtctg tgggctcttg ctgggctgtc 122820

tgcataggaa tcacctgaga gcttattaaa aataggtttt caggctggtt gcggtggctc 122880

acgcctataa tcccagcact ttgggaggct gaggcaggcg gattacttga ggtcaggcgt 122940

tcaagaccag cctggccaac atggtaaaac cccgtctcta ctaaaaatac aagaattagc 123000

caggcatgat ggcacacacc tgtaatccca gctactcagg aggctgagga aggagaattg 123060

ctcgagcccg ggaggtggag gttgcagtga gcggagatca tgccactgca ctccaggctg 123120

gctgacagag ggagactctg tctcagaaaa aaaaaaaaaa ataggttttc agtctgggta 123180

ccggtggctc acacctgtaa tcccagcact ttgggaggcc aaggcaggca gatcacttga 123240

ggtcaggagt ttgagaactg cctggccaac atagtgaaac cttgtctcta ctagaaacta 123300

caaaaaatta actgggcatt ttgacgggtg cctataatcc cagctactag ggaggctgag 123360

gcaggagaat tgcttgaacc cgggaggcag aggactgcat ctcaaaaaaa aaaaaaaaaa 123420

aaaggtttcc agtccccctg tctcagaaat tctgattctg caggtttgag gtgtgaccag 123480

gaatctttat ttttagaaga cataccagat aattctgata aatagccagt ttagggatgt 123540

agtctaattt tcctattttg caagtaagga aaataaggcc cagagaggta atgattttct 123600

caaagtcaca gaacaagtta gtggcagaat ttggactgga atgcagttct taatgttctg 123660

tccagtgttt attctggtac agtatgtttg tagaaggtat tacgtaagaa acattgttat 123720

atagatgttg agataggaag agtttacatt tagaaatttg gtctaaaatg cctgaacatt 123780

caagtcgtgg aggagtattg accaacttac tcaatacaac ataggagatt cacattttgt 123840

tacaaaaatg ctgatttaaa aggagagttt tctttttttt cttctttttt attttttgag 123900

atggagtctt gctctgtcac ccaggctaga gtgcagtgac acgatctcag ctcactgcaa 123960

cctccacctc ctgggttcaa gcggttctcc tgcctcagcc tcctgagtag ctgggattac 124020

aggtgggggc caccacgccc agctaatttt tgtattttta gtagagacag ggtttcacca 124080

tgttggccag gccggtcttg aactcctgac ctcaagtgat ccacccacca ctgcctccca 124140

aagtgctggg attataggcg tgagccactg tgcccagcct gcttgttttt gtatcatata 124200

tatgcatcat cataatcatg cattatcaac ctttgtattt ctgtcaggac atagaaacca 124260

ttagagtgct tggaagagag cctttttttt tttctcgcat ttaatgcttt ttttggtatt 124320

catttcataa tcagcttacc aaaacattac ctgcattata ccccatcaag gtagaaatct 124380

ttgtgttatc aatattggtt actccctttc cacaccgagt catcagtaag tcctgttcta 124440

tccaaatagg tcatatgcat ctagctcacc cctcagtgct gttttgtttt gaatttgtac 124500

atgtttactc ctgatgcctt gtagttatga tgatgtgttc ttattttatt ctgtgcatac 124560

aagttctcag ctcgcttttt agggaaaatg accatgtctt cctttcctat aaattccttt 124620

ctatctatca agtcctcaac agagaatagg tacccataaa tatgtgattg ttagtttctt 124680

tgcctcagtt gtagtctgat ccttacagct tttaaacaac agtagagttc accgtcaaga 124740

actaaggatg gttggcaggc agatagaaag gtagcaagtt gacccaacta tctctgggga 124800

agtgggaaca aagaaaggtt acatcagcac tgtcatcaca tagctctata gttctaggcc 124860

tgcaggctca atcaagtagc cttgtataag attctctgga ggaggtgctg aaagttgctt 124920

atacttgcta tggaatttga ttttacttcg gatatctttt taccataggt acttctccct 124980

ccaagccaca catcctcttg gatttgatga tgttgtacga ttagaaattg aatccaatat 125040

ctgcagggaa ggtgggccac tccccaactg tttcacaact ccattacgtc aggcctggac 125100

aaccatggag aaggtaaccc agaacttcaa acgtatcaaa ctacaagaag ttttattggt 125160

agaactcata aaatataagg tgggaaaacc aagcagaata gcacagtgga aattgaagca 125220

gtccagcaaa gtgattaaga gcagaggcct tgagtctggc ctggtatgta cagtcacgtg 125280

ccacataaca ttttagtcaa cagtggactg cgtgtacgat ggtcctgtac gattataatg 125340

gatcaaagct ggtagtgcaa taataacaaa agttagaaaa aataaatttt aataagtaaa 125400

aaagaaaaaa gaaaaactaa aaagataaaa gaataaccaa gaacaaaaca aaaaaaatta 125460

taatggagct gaaaaatctc tgttgcctca tatttactgt actatacttt taatcattat 125520

tttagagtgc tccttctact tactaagaaa acagttaact gtaaaacagc ttcagacagg 125580

tccttcagga ggtttccaga aggaggcatt gttatcaaag gagatgacgg ctccatgcgt 125640

gttactgccc ctgaagacct tccagtggga caagatgtgg aggtgaaaga aagtgttatt 125700

gatgatcctg accctgtgta ggcttaggct aatgtgggtg tttgtcttag tttttaacaa 125760

acaaatttaa aaagaaaaaa aaaattaaaa atagaaaaaa gcttataaaa taaggatata 125820

atgaaaatat ttttgtacag ctgtatatgt ttgtgtttta agctgttatg acaacagagt 125880

caaaaagcta aaaaaagtaa aacagttaaa aagttacagt aagctaattt attattaaag 125940

aaaaaaattt taaataaatt tagtgtagcc taagtgtaca gtgtaagtct acagtagtgt 126000

acaataatgt gctaggcctt cacattcact taccactcac tcgctgactc acccagagca 126060

acttccagtc ttgcaagctc cattcatggt aagtgcccta tacagatgta ccatttttta 126120

tcttttatac tgtattttta ctgtgccttt tctgtatttg tgtttaaata cacaaattct 126180

taccattgca atagtggcct acgatattca ttatagtaac atgtgataca ggtttgtagc 126240

ccaaaagcaa taggttgtac catatagcca aggggtgtag taggccatac catctaggtt 126300

tgtataagta cactctgtga tgttagcaca atggcaagca gcctaacgga aattctgttt 126360

attgattgat tgattgattg attgattgag acagagtttc actccattgt ccaggctgga 126420

gtgcagttgc acagtcttgg cacactgcaa cttctgcctc ccaggttcaa ccaattatcc 126480

tgcctcatcc tcccaagtag ctgggattac aggcaggcac caccatacct ggctaatttt 126540

tgtattttag tagagacagg gtttcaccat tttggccagg ctgttctcga actcctgacc 126600

ttaagtgatc tgcctgcttt ggcctccgaa agtgctggga ttacaggcat gagctaccat 126660

gcctgggcag taactgaaat tctctaatgc cattttcctt atctgtaaag tgacgataat 126720

atgcacgttt acctcaaagt tactttgatg attaaagtaa ggtaatgtat ataaaataca 126780

tattaacata gtacctgaca catggtaagc atcaaaaaat gttaactact tttattacta 126840

ttattattac gtatttttaa ataattagag agcagtatca aaaattagct gggcgtagtg 126900

gcatgcacct atagttccag ctactcagga ggctgaagct ggaggattgc atgagcctgg 126960

gaattaaagg ctgcagtgag ccgtgttcat gcccctgcac tccagccttg gtgacagagc 127020

aagaccctgt cttgaacaat taaagaaggc attatgccgc aacgttagct tagaaatgat 127080

ccacatatat caccagtaac tgtcaacagg attggaaccc tagttttggg tattatgatc 127140

acaaggtatt attaatagct tattaataat aaagcgttgg ctaggcacgg cgactcacat 127200

ctgtaatccc agcactttgg gaggccgagg tgggtggatc acctgaggtc aggagtttga 127260

gaccagcctg accaacatgg agaaacccca tctctactaa aaatacaaaa ttagccgggc 127320

gtggtggtgc atgcctgtaa tcccagctac ttaggaggct gaggcaggaa aatctcttga 127380

acccgggagg cagaggttgc agtgagctga gatcgcacca ttgcactcca gcctgggcaa 127440

caagagcaaa actccgtctc aaaaatataa ttataataaa taaataaaag taaagtattg 127500

atgtttgtga atgatttatt cttctaatga actagaggag atttttccag gaatttcaga 127560

gccagtgagg ttatgttgct tgtatgtgtc atgtgtatcc aggtgaaaaa acttaattaa 127620

acgctattat ataataccat acataaaaac tgaattttag gaatactgaa gaatgacata 127680

tagaagtcaa atcattaaat agctagtagt aaacagaata gagtgtcagc tgttacccaa 127740

tgatgataat attttcacga ttaaaattaa accttttctg attttaaagg aaaagttcag 127800

atctgtatca tataaagaat gtaaattttc agggtaataa aattaaaatg cagagagaaa 127860

aatgcaaaaa tagttcttac tagatgtgtg tatgtaagga acttagacta attttaagaa 127920

cactgtcaag accctggtag ttaggtagga aaaaagacat gaatgattca ttcaacaaaa 127980

actttgagta tttctgtgct agatggtagt gttacagtgg taaacaaaat aaatgtgttt 128040

ctgctatcct ggagcttagt ctacaaaaaa ggtacatatt ggccgggcac ggtggctcac 128100

gcctgtaatc ctagcacttt ggaagatcga ggcgggtgga tcacctgagg tcaggagttc 128160

aagaccagct tggccaacat ggcgaaaccc cgtctctact aaaaatacaa aaattaactg 128220

ggtgtggtgg cggacacctg taatcccagc tactcgggag gctgaggcag gagaatcact 128280

tgaacctggg agacagaggt tccagtgagt cgagatcatg ccactgcatt ccagcccggg 128340

ggacaaaagc gaaaatacgt ctcaaaaaaa caaaaacaaa caacaaaggc acgtattaaa 128400

tacgaacata aatatttaca aattatactg aataagttct catgtttatt atttgcttgt 128460

ccagttacaa acttttcctt cgtagaatta gaaatataaa taataaacat gagaactcat 128520

tcagtataat taataattat taaatgtaaa taaaaacatc tatgtacaat taggcattta 128580

tttaagaatt atttgaaaaa aaaacaatgt ggaaacagat attttgatat attgctagtg 128640

attgaaattg ataatgttct tttgaagagt aaagtgacca tatatattaa agttaaaatt 128700

taactcagca atcacacgcc tggtgagtta tcttaaggaa atcagtttga aagtaaaatc 128760

aatatatgca caaagacttt aacatttatc ataaaccaga aaaatcgagt ttcaaattat 128820

atcctatgga ctattttctg ctaaaaagta ttaatatcaa ctttatgtaa tactttcgtg 128880

acaaatattt tgggggagaa aacccaacaa aattacatgc attgtaattt tttttttttt 128940

ttttttttta gacagtcttg ctccagcgtc caggctggag tgcagtggtg caatctcggc 129000

tcactgcaac ctccatctcc caggttcaag caattctcct gcctcaggcc tcccgagtag 129060

ctgggattac aggcgctcac caccatgcct agctaatttt tatagttttt agtagagatg 129120

gggtttcatc atgttggcca ggctggtctt gaactcctgg tctcaagtga tccgtctgcc 129180

tcggcctcct agagtgctga gattacaggt gtaagccact gcacccagcc ttatgcatta 129240

taattttaat ttgtaaactg tacaaaggga taatacttgt agtacaacaa gaagtaaaaa 129300

catttgttat aggtagttaa catttgtaac cagtagaatt ataggtaaaa tttatttatt 129360

taaaacagtt ttagttggat ttgatttcaa ctttaaaata atgcttttca tctctatcag 129420

gtctttttgc ctggcttttt gtccagcaat ctttattata aatatttgaa tgatctcatc 129480

cattcggttc gaggagatga atttctgggc gggaacgtgt cgctgactgc tcctggctct 129540

gttggccctc ctgatgagtc tcacccaggg agttctgaca gctctgcgtc tcaggtattg 129600

actgattgcg tctgccatta gggagaaaag catacacatc ctttccttca catcccagta 129660

acagatccta ttatttgtaa attttaagtt gtggaaaaaa aagataaaag ccaggcacag 129720

tggcctgtgc ctgtaatccc agcactttgg gaggctgcgg tgggcggatc acacgaggtc 129780

aggaattcga gaccagcctg gccgacatgg tgaaacccca tctctactaa aaatacaaaa 129840

attagccggg catggtggca ggcacctgta atcctagcta cttgggaggc tgaggcagga 129900

gaatcgcttg aacccaggag gcagaggttg caatgaacca aaatcacgcc actgcactcc 129960

agcctgggtg acaaagtgag actgtgtctc aaaaaaaaaa aaaaaagaga gaaataaaat 130020

tagcctactt actatcttct aatcaaagca tttgtggtaa cttaaaatat actgtattgt 130080

aaagtatcat gctgtttcat ttaggccatt attctatttg aatctgtggc tgtttctctt 130140

aataaatcaa gtaatatgga atatattcat agcctctgaa gagctcttta tgtaagtatt 130200

tatttaggat actttttgta aaataagtga atgaattctt aggtctcctt tttttttctt 130260

ttcttgagac agggtctcct cgctgcaacc tggaaattct gggctcaaat aatccaccca 130320

ccacagcctc ctgaatagct gggactagag gcatgcacca ccacgcctgg ctaatttgaa 130380

attttttttt ggccaggcat gatggttcac gcctgtaatc ccagcacttt gggagaccga 130440

ggcaggcaga tcacgaggtc gggagatgga gaccagcctg gccaacgtgg tgaaaccccg 130500

tctctactaa aaatacaaaa attagctggt tatggtggct catgcctgta atcccagcta 130560

cttgggaggc tgaggcagga gaatggcttc aaccagggag tcggaggttg cagtgagccg 130620

agatcacgcc actgcactcc tgcatggtga cagagtgaga ctccatctca aaaaaaattt 130680

tttttttaaa tgatggagtc ttgctgtgtt gctcaggctg gtcttgaacc cctgacctca 130740

aatgccgcct gcttcagcct aagtttcttt tttttttgta aagagacagg gtcttgctat 130800

gttggccagg gtagtctcaa actcctggct tcaagcagtc ctcccacctt ggcctctcaa 130860

agtgctggga ttacaggcgt gaaccactac ctataatgtt gtgtttcact caaggccttt 130920

tgatttcgtt ttgcattacc gtgccacatt gtgcatttcc ttgacctttt ttgggttttt 130980

tggagtgctt tcatatgtta aaccatacct gattctcctc aaaatcacac aaagtagaat 131040

atcctaagac aagaaatcta aggaggcata aagaagttaa ctggttttat taaactcaca 131100

cagtaaatga tagagccaga aatattcccc ttctagtgtt cttcaccatc agcttaatgt 131160

agcataataa ttttctaatt actgttgaca aataaataac cctttgaatt ttcaatactg 131220

ggccttggat aaattttcct aatttgtaag agagtattat cgtattgcca tttacaaagc 131280

tctcctgagt atctttttct tctgttaagt ttacctagga gataaactgc tgagtatggt 131340

tgccattttg gttttttgat ataggttaga atgtcttggt tttttttttt tttttttttg 131400

gtttttgttg ttgtcattgt ttgagacagc atcttgctct gtcgcccagg ctggagtgca 131460

atggcacgat cgtggctcac tgcaacctcc acctcccggg ttcaagcaat tctcctgcct 131520

cagcttcctg agtagctggg attacaggca tgtgcaacca cacctggcta atttttgtgt 131580

ttttagtaga gaaggggttt caccatgttg gtcaggctgg tattgaactg ctgacctcat 131640

gatccacctg cctcggcctc ccaaagtgct gggattgcag gcatgagcca ctgcacctgg 131700

ctgaatgtct tgtttttgat taggcactta agaaaggcct aggtactaac cataaaatat 131760

atttttatac cttttgttga tactatatat atagaaaact gcacttatca taaccttaga 131820

caccttgaag aatgttcaca agcagaacta acccatgtga cccagcatcc agatcaaaaa 131880

cagcattatc agcccctcta gaagccctct tgggcccctt ccattcactg tccttcttgt 131940

caccagggta gctactatcc tgacttttga tggcatagat tagcattacc tgttcttgtc 132000

attttataaa taaaaccata ctgtgtattc ttttcttgta cagctttatt gtgctaattc 132060

acatttacat catacaattc agtggttttt atatggtcac agagttaggt aaccattacc 132120

acatcgattt tagaacattt ttttcactcc agatagaaac cccctttact taaactccaa 132180

atcccccact ccaccagccc taggcagcca ctagtctact ttttatctct atagagacaa 132240

tagatttgct tattctggac atttcataaa catggaaccg tatattatgt ggtcttttgt 132300

tgccaactgt ctttcactta gcatcatgtg ttcaaaagag catcatgtta tccatgtttg 132360

gcatgtatca gaattttatt cctcattatg gccaaatatc ccattgcaag gatttatgac 132420

attttatttg aattgtaccc tcctttctgc catttatcaa taatgctact gtgaccattt 132480

gtgtacaagt ttttgtgtgg atacaggttt tctttttgtt tttaaatttg aggtggagtc 132540

ttgctctgtc gcccaggctg gagtgcagtg gcacaatctc ggctcactgc aacctctgtc 132600

tcctgggttc aagcagttct cctgcctcag cctcccgagt atctgggact ataggcacgc 132660

accaccacgc ccagctaatt ttttagtaga gatggggttt caccatgttg gccagtctgg 132720

tctcgaactc ttgacctcaa gtgatccacc catctcggcc tcccaaagtg ctgggattac 132780

aggggtgagc cactatgccc ggctgtggtt ttcatttctt ttgttgtata tacataggag 132840

tagaattgct gagtcaagag gtaactctta aacttattga aaaactgcca gattgttttc 132900

cgaaaaggct gcaccatttt gcaatcccac cagcagtgta tgagttttac agcttctcca 132960

catttcattg gaacttatta tctgtttggc tgtttttaaa aatgatagtc attccaataa 133020

gttctacttc agtgtggttt ttgcacttct ctgatgagta atgatgttga gcatcttttc 133080

atttgcttat tggcctttgt tctagctttg gaaaaatgtt tattcaaatc ctttggccat 133140

ttttattttt atttttattt atttattttt ttttgagacc aagtctcact ctgtcagcca 133200

ggctggagta caatggtgtg gtctcagctc actgcaacct ccgcctcctg tgttcaagtg 133260

attctcctgc ctcagcctcc cgagtagctg ggattacatt tcaggcacct gccagcatgc 133320

cgggctgatt tttgtatttt tactagtgac agggtttcac catgttagcc aggctggtca 133380

caaactcctg acctcaggtg atctgcctgc ctaggcttcc caaagtgctg ggattacagg 133440

cgtgagccat tgggcccagc ctagattttc ttttttcttt ttttttttga gaaggagtct 133500

tgctcttgtt gcccaggctg gagtgcaatg gcacaatctt ggctcactgc aacctctgcc 133560

tcctgggttc aagcgatttt cctgcctcag cctccccagt agctgggatt acaggtgcct 133620

accaccacac ccagctaact tttgtatttt ttttagagac agggtttcac catgttggcc 133680

aggctggtct caactcctga cctcaggtga tccacctgcc ttggcctccc gaagtgctgg 133740

gattaccggc atgagctacc aggcccagcc aattttctca ttatattgcc caggctggtc 133800

tcaaactcct gggttcaagt gatcctcctg ccttggcctc ccaaagtgtg gggagtacag 133860

gcgtgagcca ccttgctcag cccctttgcc catttttaaa ttagattgcc tttttatatt 133920

gagtttcagg agtcctttat atattctaga taaatgtccc ttatcaaatt atattatttc 133980

caggtatttt cttcattctg tgagttgtct ttcctctacc ttttaaaaaa ggtgggtttt 134040

tgtttgtttg tttgtttgtt tttttaagat aaggtctcat tctgctgccc aggctggagt 134100

gcagtggcac aatcacagct cactgccacc tcaacttcct gggccgaagt gatcctctta 134160

cttcagcctc ctgaatagct agggccatag atacacacta tcacacccag cttttttttt 134220

ctgtttgtag agacagatct tactgtgttg cccaagttgg tctcaaactc taggctcaaa 134280

gtgattctcc cacctctgcc tcccagagtg ctgggattac aggtgtgagc cacacgcaac 134340

ctgtcttttc actattaata gtgtcttcct gcttcagcct cccgagtagc tgggattaca 134400

ggcacccacc accatgcctg gctaattttt ttgcattttt agtagagaca gtgtttcacc 134460

atgttcaccc ggctggtctt gaactcctga cctcaggtga ttcacctgcc atggcctccc 134520

aaagtgctgg gattacaggc gtgagccact gcacccggcc aaaatattgc cttcttaaca 134580

gtattgtctt ctaatttgtg aacatggatg tatcttcatg tatttatgtg ttctttcatt 134640

tcagcagaat tttgtagttt tcagagtaga agcctttcac ctccttgggt catttattcc 134700

tatgttttaa gttcttttcg attccattat aaatagaatt gttttcttaa tttcattttc 134760

agattgtttg atgagagagc atagaaatac aagtgatttt tacatgttga tcttgcaact 134820

tcaactttga taaatctgat tgttagctct aatagttttc ttgtggattc tttaggattt 134880

tcaatatata agatcatgtc atttatggat agagatagtt ttttttctgg ctagaactta 134940

cagagcaatg atgagtagaa gtggcagaag caaaaatctt tgtcttgttt cctatctgac 135000

agggaaagct ttcagtttca tcatttaata tgatgttagg tgtgggtttt caataaatgc 135060

cttttttcag attcaggaat ttccctatca ttcctgattt tttaaggctt tttttttttt 135120

ttaaatcatg aaagggtgtt gaatattgtc atgttctttc tgtatcagta taaatgatcc 135180

tatggatttt gggttttatt ctgttgatgt gaaatattaa ttgattttca gatgttaaac 135240

caaccttgca tacctgagat gaatctcact tggtcatggt gtataatctt ttcaatatgc 135300

tgctggattc catttactgg tattttgttg aagattttgt atctgaacgc ttaagataac 135360

atttacactc tatcagaaat gaattgacca taaatgtgag agtgtatttg tgggttcttg 135420

attctcttcc attccaaaga tagacataca tccgtctgta tgtctgtctt tatgccagta 135480

ccatactctc ttgattacta ttgctttgta ataagttttg aaatcagaaa gtataaatga 135540

gattttggta tctgagtaac agtcctcata gaattagttg ggaaatattc cctctttatt 135600

ctggtccctc tttctttttt gtttaactgt gtatcttgga gattgttcct tctcaacaca 135660

tgagagccgc tttccctacc ctcccacccc tgctatagag aggtctataa gtgtctgttc 135720

aattatttta tttacttaac ctattactta gtcggggaca ttaagcttgt ttatgtcttt 135780

tattttaaac aatgctgcag tgaataatct tgtatataag tcattttcca tcaatataag 135840

tctctctgta actgaatttt tagaagtgga atttctaggt caacctatgg ctctgtattt 135900

cacaaaaata ccaattctgg tttttcttgt ggaggtgggg agtaggaggt agaatgctgg 135960

aggagaactt gctgtactca gctggctagt cattttagaa aggtttcctt agcttctttt 136020

tgtcatatgg cctcaccaag aatcaaaaac attcctattt accctgtaaa catggggctt 136080

tactacccaa gatacatatt tctggatgta tgacagcttt tcatattgaa gaaataatgc 136140

tgtgagtaca gcacatttgt tggaacttag gtcgttaaga atgtcttata aattcataca 136200

ttatacattt tattttattt tattttttag tttttgatac agagtcttcc tctgtcgccc 136260

aggccagcgt gcagtggtac aatcttggct cactgcgacc tccatctcct gggctcaagt 136320

gattctcatg tctcagcctc cagagtagct atggttacag gcatgcacca ccatgcccgg 136380

ctaatttttt tatttttagt agaaactggg tttcaccata ttgaccatgc tggcctcgaa 136440

ctcttggcct caagtgatcg gcctgcctca gcctcccaaa gtgctgggat ccttgtattg 136500

ggtaaaagat gaatattgag ggctgcatgg tggctcatac ctgtaatccc agcactttct 136560

gagactgagg tgggaggagt cctggagccc aggagggtga ggctgcagtg agttgtgatc 136620

gcgccattgc acttcaacct aggaattata ggcttcagtc actgtgcccg gcatgtacat 136680

tttaatattg tgctttcctc ttttagctat agtatgaggt tacatttcag agtcattgtt 136740

gttaagcatc ttaatagtga tgaggttgag tgaaagttac ttctatttca aacactgaag 136800

aaaattttgt acaaatctgt cacattccaa gcccaggact gattgtttca tatacttcta 136860

attttacaat ttctattgta gtccagtgtg aaaaaagcca gtattaaaat actgaaaaat 136920

tttgatgaag cgataattgt ggatgcggca agtctggatc cagaatcttt atatcaacgg 136980

acatatgccg ggtaagctta gctcatgcct agaattttta caagtgtaaa taactttgca 137040

tcttttaaat tttttaatta aattttacat ttttttctaa tctattatta tatgcccaga 137100

actttcactt agagtgtgca gtataatgtg gtggttaagt ataaaggctc tggagtgact 137160

tcctgggttt taatcttggc tctgccattt attggcagcc gctaacctct tggtatctca 137220

gtttcttcat ctgtaaaatg agaataataa agtgaaaaga tgccaacatc atttactctg 137280

ggctgcataa ctgatacttg gaaaaagtat tcctttgagt ttaagaatta agttggttat 137340

tcattttagc ttgtaataaa aagatagtga ttcataggat atgccactta ctgaaattta 137400

ccacagatcc aatcataaaa tcactttctc ttccctaaag atagcttgat taacatgtaa 137460

aggtgtgtaa aggcttgatt acactaccct gatccgtacc ccagttccca gcagcaccat 137520

gaaaaaggga tttcaacata tttaattact ttcagtagaa agtaacagtg gtaggccagg 137580

cgcagtggct cacacctgta atcccagcac tttgggaggc cgaggtgggc ggatcacgag 137640

gtcaggagat tgagaccatc ctggctaaca cgatgaaacc ccgtctctac taaaaataca 137700

aaaaattagc cgggcatggt ggcaggcacc tgtagtccca gctacttggg aggctgagac 137760

aggagaatgg cgtgagcccg ggaggcggag cttgcagtga gcttagattg tgccactgca 137820

ctccagcctg cgcagtggag cgagactctt gtctcaaaaa aaaagaaagt aacagtggta 137880

ttgggagact gaggagccta gaaagtactt gaaggaagta aaaggtttgt ttgaccacat 137940

tgtatttgga aagccagctt tttcagctgt gtcagctttg tgtagtgatt tttagttctt 138000

cttttagaaa ataacggaca aggccgggca cggtggctca cgcctgtaat cccaccactt 138060

tgggaggccg agacgggcgg attacctgat ctcaggagtt cgagaccagc ctgggcaaca 138120

tggtgaaacc ccgtctctac taaaatacaa aaagttagcc gggcgtggtg gcgtgtgcct 138180

gtagtcccag ctactccgga ggctgaggca ggagaattgc ttgaacccgg gaggcggagg 138240

ttgcagtgag ccaagatcac accattgcac tgcagcctgc gcgacagagt aagactctgt 138300

ctcaaaaaat aataataaaa taaaaaagaa tggacagtaa acctaaatga gttcattccc 138360

aaagatgatg ttattcttaa gggatggttc atttatttaa gaccttacat aaagtctatc 138420

aattgcgtga tttttcactt ctgtaattgt gtgtatgtat aatgtaaata tatatgtttt 138480

tgttttgttt tggttttttg agacggagtc tcgctctgtt gctcaggctg gaatgcagtg 138540

gtgcaatctc agctctctgc aacctctgtc tcccaggttc aagcgtttct tctgcctcat 138600

cctcccaagt agctgggact acaggcacgt gccaccacgc ccggctaatt ttttgtattt 138660

ttagtagaga tggggtttca ccgtgttagc caggatggtc tcaatctcct gacctcgtga 138720

tccacccgcc ttggcttccc aaagtgttgc tattacaggc atgagccacc acacccagca 138780

tgtatttttt aaatgtataa aatgaagcag aaaagagaaa tgataatttt tcttcatctt 138840

gaaagattat cttcaccagg cgcagtggct cacacttgta atcccagcac tttgggaggc 138900

ctcggcaggc ggctcacttg agttcgaaac cagcctggcc gacatggtga aactccgtct 138960

ctactaaaaa taaataaata aagatggttt taatatatgt tttagtttta tgattttagc 139020

atctttctga aatttttctc aaggcaagta aatttgtatc agttggtata ttggtaccca 139080

tctatgaaat aacttattag gaagatatct ctaaaataag atcactttgc ctaaaataaa 139140

ctgatatatt gatgttcaca gaatttttct tttaaccgac ttgataaatg cattattctt 139200

gacgtcaagt gatccacctt cctcagcctc ccaaagtgct gggattacac acatgagcca 139260

ccgcacctgg cattattctt ataaaaggtt aaatttctag ttaagtttaa tgtcctcttt 139320

gttcatgtac cattgcttat tttcttccct tcctactcac agtaatcatt cttatggtat 139380

gcacttttgt ttgcttattt ttatgtaatt gatattacgc tccattctgt acgttgtact 139440

ttcattcaca gtgagttttg gacattccta tgttcatcta tacagactta cttcatttta 139500

actacactgt agtattccgt atgtaatatt tactataact catcactgta gcagagcatc 139560

tcatagtgta tgtattactg ttttgccatt ttggtatcaa tgagtattta agtcatttgc 139620

agtttttccc tcttataccc agtattacag aggatctctt tttatatgct tctttgtacc 139680

aagaggcaga ttaaaaaatt tttttttgaa aaaatttttg aaaaaaaatg aaatgaagtc 139740

tcactatgtt gcccaggctg gtctcaaact cctaggctca agcaatcctt ccatcttggc 139800

ctcccaaagt gctggggtta caggcatgag ccaccatgcc tggcctacat tttaaatttt 139860

gatagctctt acaatttact ttgtaaagta tctgcatcat tttatgttct caccagtctt 139920

taataagaat acttcatact tttggctgga cacagtggct cacgcctgta atcccagcac 139980

tttgggaggc cgaggcgggc agatcaagag atcgagacca ccctggccaa tatggtgaaa 140040

ccctgtctct actaaaaata caaaaattag ctgggcgtgg tggcgcaccc gtagtcccag 140100

ctactcgaga ggctgagaca ggagaatcac ttgaacccgg gaggtggagg ttgcagtgaa 140160

cttagatcac accactgcac tccagcctag caacagagtg agactctgtc tcaaaaaaaa 140220

aaaagaatac ttcagactta attttttttc cagtcttaag tgtttgctaa tgagattgag 140280

tttcttttgg tatgtctctt gattgttcag gttttttctt ttatgaattg actgttcatc 140340

tctttttcac attatttctg ttgggtgatt ttattagtga cttgttaaaa ttctgtatat 140400

tttttcagca tgacacttca ttattcaaaa aaaaaaaaag attctctatg tttctcgata 140460

ctaatcattg gttggtaata ccttaaaaat aagaccctta ctgtattttt tgcttttttt 140520

tttttttttt tttttttttt tttgagatag agtcttgctc tgttgcccag gctggagtgc 140580

aatggtatga tctcggctct cagctcactg caactgcaac ctctacctcc ctgtttcaag 140640

caattctcct gccttagcct cccaagtagc tgggattaca ggcatccacc accacaccca 140700

gctaattttt gtatttttag tagagacagg gtttcaccat gttggccagg ctggtctcaa 140760

actactggcc tcaagtgatc cgcctgcctc ggcatcccaa agtactggga ttacaggcat 140820

gagccacagt gcctagccac tttttgcttt ttaactttgt tttatagtac tatagtttta 140880

gtataaacag atgtatgtat acacacaact atggctttat aatatgtttc agtcattgtt 140940

agagcaaggc ctaccttttg ggtgcttctt ttacaaaatt gtcttggcta ttcttgtgcc 141000

ttttttctta tttgtgaatt ttagaattgt gaattacctg ttgactcacc atgttttgta 141060

aactgaggat tttgaatgga attgcactca attaaagatt atcttgcttt ctgtgcagca 141120

atgttttatt tcaaataatc cctactttaa attacttagg atagctataa attgtgtttc 141180

tggctttcta gatttagatg aaacgcttta aattgattgt tttctcctaa atttaaaact 141240

gattgttaga agttaaagtc ttctgttcat tcttatttag gaagatgaca tttggaagag 141300

tcagtgactt ggggcaattc atccgagaat ctgagcctga acctgatgta aggaaatcaa 141360

aaggtttgtg gtgtttttat acttcatatt aagcctttac tcacattagt gattgactgt 141420

aagtcaaaga ccacttaagg tttaaactgt ttattttgta aagtaaccac tgtatctttc 141480

accttgtgtt tatagtcaga agtaagtaca agggcttcct gtagtcacat ctttatgcaa 141540

tctcctctga atcaaaagtt agtgaacttg ctttgccact ccagaaggca catgaatatg 141600

aaaaagcatt gtctattttc ttatttaatg gcaaaatacc cgacctaagt tggacttaat 141660

gtttgagacc gtttatttta ttaaattata ttttttctct tttctttttt ttttttgaga 141720

cagttcttgc tctgtcaccc agaccggagt gcagtggtct gaccgcacct cactgcaacc 141780

tctgcttcct aggttcaagc gattttcctg cctcatcctc ctgagtagct gggactacaa 141840

gtgcgcacca ccacacctgg ctaatttttg tatttttagc agagatgagg tttcaccacg 141900

ttggctaggc tggtctcata ctcctgacct caagcaatcc atccgccttg gcttcccaaa 141960

gtgctgggat tacaagtgtg agccaccatg cctggcctta ttaaattatt tttattaaat 142020

ttcctcaaga ttgatgaaag taatgaaata taaaagtaat gaaatatatg tggaaaatag 142080

actggattaa gaaaatgtgg cacatataca ccatggatac tatgcagcca taaaaaagga 142140

tgagttcatg tcctttgtag ggacatggat gaagctggaa accatcattc tgagcaaact 142200

gtctcaagga tagaaaacca aacaccgcat gctctcactc ataggtggga attgaacaat 142260

gagaacactt ggacacaggg tggggaacat cacacgctgg ggcctgtcgt ggggtggggg 142320

gctgggggag gaatagcatt aggagatata cctaatataa atgacgagtt aatgggtgca 142380

gcacaccaac atggtacatg tatacatatg taacaaagct gcacgttgtg cacatgtacc 142440

ctagaactta aagtataata aatttaaaaa aaataaatat atgtggaaaa tattaatagg 142500

tcaaaattca aattgttcat ttaatcagaa gagtagttta gtcaaatcca agggttagac 142560

aacagaaatc ttttttgtca agtgcattct ttgtgactga tttcattttc ttcctggttt 142620

acacaggaag atttcagaaa caaatgtgga tccgtgacag atggtatcta gaagttttta 142680

gtttggttga attgacagta ttttattgag taaaagatac taatttttgt aagaagaaaa 142740

attcaatttt gataagtatg tttaagatta agagctattg gccaggcgct gtggctcatg 142800

cctgtaatcc tagcactttg ggaagctgga gcaggtgggt cacgaggtca agagattgag 142860

accatcctgg ccaacatggt gaaaccctgt ctctactaaa ttagccaggc gtggtggcac 142920

atgcctgtgc acccgcctcc gggtttaagc gatcctactg cctcaggctc ctgagtagct 142980

gggattacag gcgccatggc taatttttgc atttttagta gagacagggt ttcactacat 143040

tggccaggct ggtctggtct caaactcctg acctcaggtg atctgcccgc cttagcctcc 143100

caaagtgctg ggattacagg catgattcac catgtctggc catttatctt attttctttt 143160

tttttttttt ttttgtttga gacggagtct tgctgtgtcg cccagagctg gagtgcaatg 143220

gtgcgatctc agctcactgc aacctctgcc tcctgggttc aagcaattct cctgcctcag 143280

tcttccaagt agctgggatt acaggcgcgt gccaccacat ctagctaatt tttgtatttt 143340

tagtagagac agggtttcac catgttggcc aggctggtct cggaactcct gacctcgtaa 143400

tctgcccacc tcggcctccc aaagtgctga gattacaagt gtgagccact gtgcccagcc 143460

atcttatttt ctttcttttt ttttgtcggg tgggaggggg acagagtcta gctctgtcgc 143520

caggcttggc tcactgcaac ctctgccccc caggttctag caattattct gcctcagcct 143580

cccaagtagc tgggattata ggcacctgcc accacgcctg gctaattttt tgttattttt 143640

agtagagatg gggttttgct atgttgacca tgctggcctc aagtgatccg cccaccttgg 143700

cctcccaaag tactgggctt acaggcgtga gcttgtattg ggtaaaagaa caatattggg 143760

ggctgcatgg tggttcatac ctgtaatctg agcactttgt gagactgaga tggaaggagt 143820

gttggagccc aggagggtga ggctgcggct gcagtgaatt gtgatcacgc cattgcactt 143880

ccacctaggt aatggagcaa gaccatgtct ctaaaaaaca aaacacaatt tttttaagga 143940

atactgggaa gaggtcagtg gtggttttag aacagaggaa gtgccagatg acctttgtga 144000

ggcattggcc aggaagaact ctacagtgtc tttaggtagc ttctgtccat aaggataatg 144060

gggtctcctc cccagtatta atagaaaatc tctgagctgt ttttttttgt ttgtttgttt 144120

tgtttttttt tcctgagatg gagtctctct ctgtcggcca ggctggagtg ctgtggcgcg 144180

atcttggctc actgcaagct ctgcctccca ggttcacacc attctcctgc ctcagcctcc 144240

caagtagctg ggactacagg tgtccaccac cacgcccagc taattttttg ttatttttag 144300

tagagatggg gtttcaccat gtcagccagg atggtctcga tctcctgacc tcgtgatccg 144360

ctcgcctctg ccttgcaaag tgctggagtt acaggcgtga gccaccgtgc ctggcctggt 144420

ttttttgttg ttgttattta tttatttatt tatttatttt ttgagacaga ctctcgctct 144480

gtcgcccggg ctggagtgta gtggcacgat gtcggctcac tgcaagctct gcctgccagg 144540

ttcaagccat tctcctgcct cagcctcctg agtagcaggg accacaggcg ctcgccacca 144600

cgcccggcta attttttgta tttttagaag agacggggtt tcaccgcatt agccaggatg 144660

gtctcgatct cctgatgtcg tgatccgccc acctcggcct cccaaagtgc tgggattaca 144720

ggtgtgagcc accgtgcctg gcctgatttt tttttttttt taatctggtc tcatacctct 144780

gacagctcat gaagaagtgc tcctgcttca tatgtatatg tgttagcata gtgttaacat 144840

agcataggtg ttcggtgttt gcagtttctg tttgttttat atgaattaag gtgtattatg 144900

agcagttgaa gatatatagg aaattttttc ccaaaccact atctctgctc gttctattca 144960

ttcagtctgt ttatgttatt ccttcattca ttcattttat agaacagtgg agtgcctact 145020

gtatgcatct attgttctgg gtcctgggga agaaaacaaa gttcctgctt tcatggaact 145080

tacattatat tggcggagac agtaacagac aaacaaatgt agcctgtgta catgtgttac 145140

atgaaaagca gggtaggggg ctgggagaga gtagtaggga gtgctatttt cgaggtggtt 145200

gtcaggaaag gcctcactga ggaggtggca ttttgagtag acctgagcgc agcgggggcg 145260

taagcccagg cagcatgtgg aggaagagtg ttcttggtga aaggaacaag gatagaggcc 145320

cgaagctaga gagctcagca tgatcaagga acagcaagcc ccgtgtggct ggaatggagt 145380

gagcaaagga atgagcagta gaaggtgagt gagttgggag gtcaccagag accatggcaa 145440

ggacttgaaa gtgtcaggga cacattggaa gttggagcag ggaaatgatg ggatttatgt 145500

tttgtttttg ttttatgttt agtgttttta agggattgct ctatcagcta tttggaaaat 145560

ttagtgtagg gcttcaagaa gagaagcaga gaaacaacat tcttgccata gtcatagtct 145620

aagtaaggga tgatggtggt gtggattagg ctggtagtgg aagaccagtc cagttcgggt 145680

tgtatttgaa ggtagaggca aaaagattat atttctacca gcaagcccat ctatgaagtt 145740

acttgtatta ttaatttaat tgagacatgc ccacataaac taataaatag gaatttctgc 145800

agtttggtta aacacccctg tatatcctgg ttcttctttt agttgtccag atgtctcttt 145860

aagtcaagta ttttttggtg gtgtaggagc ctagagattg aatttattca cccaaaaggc 145920

atttgagtga ttactatgtg ccaggcacta tgctgaatgc caaggatgta aataagaggg 145980

cgtagtctca gtctgtttta ctccagcttg gttccttttt aatgaccctg acttgttaag 146040

catatcagtt atcctacaga atgtttaatc ttctgtactt tcctggttgt gttatttagc 146100

ttatttctct ttccttgaca tttcttgtaa actggaagtt acacctatag tcttgatgat 146160

tcgtgttaca cattttagat tagaacacat catgtgttgt atatggtgtt tttgaaagcc 146220

tctctgtata ttggtctgta cattaaaatg ttgcctgaat ggatacacat aaaatttaac 146280

agtgattaca ttagagatga gaagaaagag gtgcctttta cttttcaata taccttttcc 146340

tctgcttttt gaactttctt gccctatgca tacgttattg cttaatcatc cacctcatct 146400

cttcccctgt ggctttctgt tgcatttgga atgaaatcta gcctctttgc tgttacctgt 146460

ggatgtccct tgctggcctc tatcacctta ctttgaacca ctcctttcat ggactgagct 146520

ctcattggac tatcttttat tcttttgctg aagtttcttc actttgagtg cctctgcagt 146580

tgctatttca tggctgtggc aagccctgcc atggctttca tgcaaggatg gttcctcctt 146640

ctcatctcaa tattatctct tcagagaggg accttcccaa ctccgatgat ctaaaatcct 146700

ttgtatatac cactcactac cacttctttc ttttcttttc cttttatctt tttttttttt 146760

tttttttttt gagatagggt cttgctctgt tgcccaggct ggaatcacga ctcactgcag 146820

cctcatcttc ttgggctcaa atgatcctct cacctcagcc tctcgagtag ctggaactgc 146880

aggcacacac caccatactt ggcttattat tttacttttt gtagagacag ggtttcacca 146940

aggctggtct caagctcctg ccgcaagcaa tccacatctc tcagcctccc aaagtattgg 147000

gattatagga gtgagccact actcctggcc tattttctta ttcactgtct aaaattatct 147060

tgttcattta tttacatact tgtttatagc ttatttctca gctggacatg gtgcctcaca 147120

cctgtaatct caatactttg ggaggctggg ttggagaatt ggttgagccc aggacttcaa 147180

gaccagcctg ggcaacaaag tgagaccctg tctataaaaa attgtttaaa aattagctgg 147240

gcatggtggc acatgcctgt ggtcccagct acttgggagg cagaggtggg agaatcgctt 147300

gggcccagga ggttgaggcg acggtgagcc atgattgtgc cactgcactc tagcctagtg 147360

acagagtgag accatgtgtc taaaaagtaa ataaaaatag tttctctttc atgactagaa 147420

tattacctct atgtgggcag ggagtttgtc tatactattt ggcactatat ttcctgattc 147480

tgaaattatg cctagcacat ggtaagtact ccttaaatat ttattgactg aattatttaa 147540

tacttaagaa tttcatttgg gattatctga gtggtaagat tacggattat atttatgtaa 147600

gaaaaaatca ttttttaaac ttggttgccc tttgccacac tgacatagac actaagtttt 147660

cttagccaga ttacttccga ggatactcac agaggccatt ctcttctcaa tccccaaata 147720

attgatattt cttagcactt tcaagctaat gcaattctta gatgatgtat ctgtgtatat 147780

catatcctca ttctacaaat gtagaaattg aagtctgggc acagtggctc tcacctgtaa 147840

tctcagcagt ttgggaggcc aaggcgagcg gatcactgag gacaagagtt aagaccagcc 147900

tggccaacat ggtaaagcct tgcctctatt aaaaatacaa caattagggc cgggcgtggt 147960

ggctcacgcc tataatccca gcacgttggg aggccaaggc aggcagatca cgaggtcagg 148020

agttcgagac catcctggct aacacagtga aaccccatct ctactaaaaa tacaaaaaat 148080

tagccaggca tggtggcacg cgcttgtagt cccagctatc gggaggctga ggcaggtgaa 148140

tcccttgaac ccgggaggcg gaggttgcaa tgagctgaga ttgcaccgct gaactccagc 148200

ctggtcaaca gagggagact ctgtctcaaa aaaaaaaaaa aaaaacaatt agccaggcgt 148260

ggtggcgggt acgagtacct gtaatcccag ctactaggga ggctgaggga ggagaatcac 148320

ttaaacccag gaggtggagt ttgcagcggg ctgataatgc accactacat tccagcctgg 148380

gcaacagagt gagactctgt cttaaaaaaa aaaaaaagaa agaaagaaat tgaggaatgt 148440

ggagattgtg gtctgtgatt tgttaggaat cacacagcag gttagtagca actacagggc 148500

tttggttcag aataccacct tgacaatggt ttgtttacag ttcggctccc cttcctctgc 148560

ctttctctcc ttccttattg agggcagctg gaaagaattt tcatcattta ctagcctata 148620

gctttaattt gagttttgaa accttgataa tagagcacag aggaaaagac tgagttttct 148680

ttttttgaga cagtcttgct ctatggccca ggctggagtg cagtgacacc atctcagctg 148740

gttgcaacct ctgcctccca ggttcaagca attctgcctc agcctctcga gtagctgaga 148800

ttacaggcac gtgtcaccac gcccagctaa ttttctgttt ttgtttcgtt ttgttttttt 148860

ctgagatgga gtcttgctct gtcacccagg ctggagtgca gtggtgcgat gttggctcac 148920

tcaaacctct gtctcctggg ttcaagcaat tcttctgcct cagcctcccc agtagctggg 148980

actacaggta cgtgccacca tccctagttc atttttgtat gtttagtaga gatggggttt 149040

cactatgttg accaggctgg tctcgaactc ctgatctcag gtgatctact cgtctcagtt 149100

tcccaaagtg ctgggattat tggcacacgc ctatttttgt atttttagta gagacggggt 149160

ttcaccatgt tggttagact ggtctcaaac ttctgacctc aagtgatttg cccgccccag 149220

cctcccaaag tgctgggatt acaggcgtga gccaccgtgc ccagccaaga ttgagttttg 149280

aaaagagcct tctgagatta tgagaagggc aagcaagata acttaagaag ttacattaaa 149340

atcatctaag agacagtgta acaagaagga attgtaaaat gatgttatga gcacgtgccc 149400

aatgtagtgg caatcccttg tgcttcgata cattggtggg agacaaaact gtacttaaat 149460

tgataaatcc cttacatgtc attttaagga gcttagactg actcccatca tgtagacatc 149520

agagatttct tttttttttt tttttttttt tttttttttt tttgtgacag agttttgctc 149580

ttgttgccga ggctggagtg caatggcgtg atctcggctc accacaacct ccacctccca 149640

ggttcaagca attctcctgc ctcagcctcc cgagtagctg ggattacagc catgcaccac 149700

cacgcctggc taattttgta tttttagtag agacggggtt tctccatgtt gtggctggtc 149760

tcgaactcct gacctcaggt gatcctcccg cctcagccac ccaaagttct gaaattacag 149820

gcgtgagcca ccgcgcccag cccagagatt tctaaacaga gttctaacca gatgcttttc 149880

cctgtcagta gaatgagaat gaattggagg tgggagagac tggcatgagg gacaccagtc 149940

agccagtgga attagctggt aatgttgata ggagaagaaa aagattcaaa gttaggtagt 150000

ggtagcaaga attagaggga aggtcggatt tatgatatgt ccaaggttga attctaaggt 150060

gaaatttggt ggcagatttc atgtgtaaat tgggaaggta gattgagttt ttttaacatg 150120

ggttttctaa catgtcaata gagtgactct gcaggggggc ctgacgagag aacagtgcat 150180

ggggtgattc aacagccagt tgagccttca tgcagagcat ttaacactgt gactctgtag 150240

actctggttg gcagtaaaat ttcattaaac caatatttaa acccttaggt aataataaaa 150300

attgagggaa aaggatccag gttttgtatt ttttatgaat tcagttattg aattaaacag 150360

gaccttgcct caagaaataa tctaccaaca attaacttgt tttaaagcaa agttaggaag 150420

tgagcatgtt caaattatta aataaaaaag taagctgtgt atttcattca tagaaataga 150480

ggctggccta cttcggatga ttctcagcat gtgattacag atgtgggctt atacatccta 150540

gggagttaag gcgtactctg gcttggatag agtagagctc tttgaaactc ttctctcacc 150600

cagctagttt atatagacta gagaactaga atgtagcagc atactctgtc ttagaagccc 150660

ttttatatag gagctggtct ggaaggtttg aaaacataac aaatgtgttg gtgtctccca 150720

atgtattgct agattcttac ccaagagcat tatcctggtt agggtttggt ttggttttgt 150780

tttgtttttt aatgtttgcc acaaactaac actagatgtt agttctttca tcaagtgagg 150840

agagtagaag aaaagtccag aactctgaaa caccttttca aaagtttttc aagccatgat 150900

gtttgcaagt taaatgctct gttatgtaag caatataatc agtttttatt aatgtaacat 150960

tccttagtgt tttggggtat cacacaaaaa agaatatcca tatctggaag caacagcttt 151020

taaataagag cattgtggtg gtggtggtga tagtggtttt tttttttttt tttgagttgg 151080

agtctcgctc tgttgcccag gttggagtgc agtggcacga tctcagctcg cttcaacctc 151140

tgctcccagg ttcaagcaat tcttctgcct cagcctcctg agtagctggg attataggca 151200

cctgctacca tgcctggctg atttttatta ttttagtaga gacaggtttc accatgttgg 151260

ccaggctggt cttgaactct taacctcagg tgaatcaccc acctcggcct cccaaagtgc 151320

tggaattaca ggcatgaacc accatggcca gccaaataag agcattttta atgtaaaatt 151380

atgcatgaaa tgtacattca attttgtctt tgtttactag gatccatgtt ctcacaagct 151440

atgaagaaat gggtgcaagg aaatactgat gaggtaaatc ctacctttag gataaaaaga 151500

tttctgttta taagtgccac cctcatgtaa gtgaggttta aaattttcct tttctttagg 151560

tcccatgttt aagcagcatg gcacatttat gttctcttac ccagaatgta ccaagaaagg 151620

gtggtccctt cttaacatct aacaattgcc tggtagtagc agtgaaggta tcttcagtca 151680

gaggctagga ccactgaagg atatacatgc attcaagttt ccatcagcca gcaggcatca 151740

gtaatcagtg tgtagatcaa aagctcaaat gtttccttcc ccactggcag ttttacttca 151800

agtagtggag gcttgctttt ttaatagtta attaagtaca ttgagagatg ggaggtgaaa 151860

aaaggaaaat gttttatttt gaccatctaa tatgaaagta gttcggtgtt aggtatccag 151920

tagttgacac tggaagacag ggaatgacat gttaatattc atagccagag ggtggcccag 151980

gttttttcgt acatgggaat gaaattctta tccaaataag tagaaattat gtgcgtaagc 152040

catttgttaa gagcactgag tatgtgcatc tcgatccatc taatgaataa ccattatcac 152100

cagtttaaat tattttcttt aggcccagga agagctagct tggaagattg ctaaaatgat 152160

agtcagtgac attatgcagc aggctcagta tgatcaaccg ttagagaaat ctacaaaggt 152220

aaggatgact tcgttttgtg taaactaaaa agtattattt tccaggtgta aaaataaaaa 152280

agaacataag gggtttcttt gcctttgaag gattaactgc tgtggggatt accttcttat 152340

cataagcaac tagaaaattg acaaactaaa tgaaacaact gtttgcatat attggacaat 152400

gggcaataca gggaaaccat ggaaaccaaa cagagcccag tagtcttgct gaacgaaaga 152460

gttaaatatc aaagttcagg ccaggtgcag tggctcacgc ctgtaatccc agcactttgg 152520

gaggccaagg cgggtgaatc acttgaggtc aggagttcaa gaccagcctg gccaacatgg 152580

tgaaaccctg tcttagccgg gtgtggtggc aggcacctgt aatcccaact atttgggagg 152640

ctgaggcagg agaatcgctt gaaccaggga ggcggaggtt gcagtgagcc gagatcacac 152700

cactgcactc cagcctgggc gacgagcgaa accccatttc aaaaaaaaaa tcaaagttca 152760

gagagctcaa tttgagtaga agttgtagga taaggtagca gaaaagagga agctgcccag 152820

aaagaaagcc gtagagatat ttagagagat tcccatggat ccttggccta ggagtgatct 152880

gtatatgtgt ggggtgaaaa cgcatgtgtc caggtagaga accccccaga aattagtagg 152940

ctgaatgatt gctggaacat agggctaaga aaagttcatg gccagaagga tctggccaga 153000

gtagagagac ttagtaatac acaaggcatt gggtagtgtc ttcacagagg ttatgcctta 153060

ctactgaaga taaattagtc ctagagtaca agcacctgaa ccaagtttca aagcaaattt 153120

ttaaagggtc aaattaccta acaactgcat gccaaaacaa aggcctaacc ctctttacag 153180

taacacaaca aaattcagca cttcacagtg taaagttaga atgtctgacg tccaggctgg 153240

gcgcagtggc tcatgcctgt aatcccagca ctttgggagg ccgaggcagg tagatgacct 153300

gaggtcagga gttcaagacc agcctggcta acatggtgca accccgtctc tattaaaaat 153360

acaaaaactt agccaggcat ggtggccggc acctgtgatc ccggctactt gggaggctga 153420

ggcaggagaa ttgcctgaac ccaggaggtg aaggttgcag tgagccgaga tcgcaccact 153480

gcactctggt ctgggcaaaa agagcaaaac tcaggctcaa aaaaaaaaaa gaatgtctga 153540

cgtcaatcac aaattaccaa gcatgacatg aagttgacct ataaccagga gaaaactcaa 153600

tctatagaaa cagacccaga tgtgagaaag atgatgaatt tagcagacaa agaccatcaa 153660

gtggctattt taaatattaa aaatatgttc aagtggccag gtgcagtggc tcatgcctgt 153720

aatcccagca ctttgggagg ccaaggtggg taggagttca agaccagctt ggccaatatg 153780

gtgaaacccc ttctctacta aaaatacaaa aaaattagct gggcatggtg gcaggtgcct 153840

atagtcccag ctatatggga ggctgaggca caagaatcac ttgaacccgg gaggtggagg 153900

ttgaggttgc agtaagccga gattgtgcca cttgtactcc agcctggaca acagagtgag 153960

actctgtctc aaaaaaaaaa aaaaaaaagt taaagaaaac aagagtataa tgagaaaaat 154020

gcaaaatagt tttaaaagaa ccaaatggaa tttcttaaaa taaaaaatac cagaaatggg 154080

ggccgggcgt ggtagctcac gtctataatc ccagcacttt gtgggggctg aggcaggcag 154140

atcacctgag atcggtagtt caaggccagc ctgaccaaca tggagaaacc tcatctctac 154200

taaaaataca aaattagctg ggcgtggtgg cgcattgcct gtaatcccag ctacttggga 154260

ggctgaggca ggagaattgc ttgaacccgg gaggcagagg ttgcggtgag ctgagattgc 154320

accagtgcac tccagcttgg gccacaagag tgaaactccg tctcaaaaaa aaaacaaaaa 154380

aaaacagtag actcgaagaa ctagctgagt ttttctttac tttaggcagt aagtgtgacc 154440

ttttgcaggt gactacttta gttcctcatg tcctcattag tagatcagag aaattcgaca 154500

ccaaaacccc aaaagaaaaa ccccttctaa tcctcattcc atgattttat gaatgcatga 154560

agtcctaggc ctgcgaagga atactcattc tctttatcct gtgttgatac ctctctgctt 154620

caacctccaa ctcgacattt gcctatagga tgtacttgga cattcagcat aaactacctc 154680

acaccattac tgaattgctt catgtgcaca tgtcccatgc cacaataccg gggaccttgt 154740

cttccgtgat atttgtccgc agtgctgtga ctacaggagg gagtcagtga atgtctgcat 154800

gtgtgtcttt accatccctc ttgaatatgc tctagggtta attcctagaa gtagaattac 154860

tctattgaaa attggcaata tttttcattc taatatctat tgccaacatg ggaaagcaag 154920

tctggatgcc agtccttgtt atatgcccct tgggtaagtt acgtaacctc tttaagcttc 154980

tgttcactca tattttaaca aggaaaatta caatatttta cctcacaaaa ttgtagtcag 155040

cttctggctg tcttaaactc tggtatatag taaacactaa gtgttggtgt ccatccttaa 155100

tttgtaataa taggtcactt gttagagaaa tgcaccttac cattttcttt tcttttcttt 155160

tttcagttat gactcaaaac ttgagataaa ggaaatctgc ttgtgaaaaa taagagaact 155220

tttttccctt ggttggattc ttcaacacag ccaatgaaaa cagcactata tttctgatct 155280

gtcactgttg tttccaggag agaatgggag acaatcctag acttccacca taatgcagtt 155340

acctgtaggc ataattgatg cacatgatgt tcacacagtg agagtcttaa agatacaaaa 155400

tggtattgtt tacattacta gaaaattatt agttttccaa tggcaataac ccatttatga 155460

gagtgtttta gcctactgga atagacaggg accacatcct ctgggaagca gataagcata 155520

gaactgatac ttgatgcaca ctcgtagtgg taactcatcc ctaatcagca ttgtaaagca 155580

ggtgccagag gtggtttgct ttgtccttcc aaagcaggtg agtcagcccc accgagagcc 155640

aggcagcttt gagtggcagc gtggtgctag cagcttcagc ggaacagggt gagagttaat 155700

tatgcagtct tcttgacagc ggcattaatt tggaaggaaa ctgacaagtc atgggtcaag 155760

tttcagtgac ttcctccttc ctctgatggc agtatatagt tttcacattt taattcctcc 155820

tcctgagatg cactatactt aaaaccattc tctcccctgc taacagaagg gtgtgaatct 155880

ggtttacttt gagcattagg atttgcccct ttggaattct gcactccagt tacttaactt 155940

tcccttcaga atacatgtgg aaagaaagaa agaaatagcg atgactccac ttttgcccct 156000

gtggcacctt gaacaaagca gttcttccca aattatactt tttttttttt taaataaggt 156060

gagcaggatg actggggaga gagaaacatt tgactttgac tgcctccccc attctttgct 156120

gtgagctgga aagtgtgcag ttggtcgtct ttcttctcct ttctttagga tagtaagaga 156180

ctcactcact gcacttctgc tcagttggct tctgcatcgg gatcacacag ccatcagcag 156240

gactgcccag ttggtgagca cactccattg accacgtggc gccagcgctt cctcaatgca 156300

catgattgag aggaaagaaa gttctcttag atgttactgc ttttgctcag actttgcaaa 156360

aaaaaaaata tatatatata tgtataaata tataattatt aatcactttt gtccttgaga 156420

aagtcttgaa tgaacagaga atttattcca ttgcaatatt tgattgtata gaggcacact 156480

gtttcatcga cagaagaagc aaaaaggctt tgtgtaagtt tttggtacta tgtaccacct 156540

ctgttattct tttaaagctg aagtattcat gtacttaaac catattatat ttaattgtgt 156600

ttgattttaa aatatatata tatgaattct atttaaaatt gtgtcaactt tctgctttca 156660

gggcatttat ggctcttctg ttgaaatata ttgatctttc caaatatttt catttgcttt 156720

ctaaaaaccc agaacatgag ccactactgg actttgcctt gtgtttgaag tgtatggcat 156780

aaacccaagg tttttattag tcatctatgc tgtgattaat tcattttgtt cttttaacaa 156840

aatatttcca tccacttcac attgcttcaa tctttaacag aaaagcaata taaaggttat 156900

agaataaaat gtggttttgg gcaactcttg ctgcctctgc atgttttgga ataacaattt 156960

ctacaagact ctaggctgtt taaactagtg ctttcagtta agataaattc taatcatttc 157020

tttgtatata cattttgtgc ttctgagcta gagatgccaa gtagttgtaa actgcttata 157080

aagagaatag cagcaaattt gagactcggc tacttttttc tgccccacct gctttgagac 157140

acagaagcgg agtgtggccc gaaattatta gccagattta atatttgatc taaagtaggt 157200

ccttgtactc attttaaagt tggaatttga ttcctccaac attgagcacc caccatgttc 157260

caggctctgt gcattgtgcc cacaaaataa gattccctgg tggagttttt atgggttcaa 157320

ataatcagtt gaacaccctt catctttatc atgttgttga cattgacaca aattgtttaa 157380

aaagaaaaga tattagagag aaagtggtac ctttgtaact tgatgtgtct tcatcattcg 157440

gtaagatttg atgaaagtaa aaagcaaatg tcagccaaat ccagtgaaca gcaataaaac 157500

agggagtaac tttttataac tttttctact tggatttcaa cattcagtag agcttttcga 157560

aatgtaagta gtttacagta ctggaggttt gactagttca gtaggaattt ggaggggaag 157620

gtcattctga attgtaacaa agtacaaact tctttgctgt tttatttaag tactgagagc 157680

taagcacctg atgaagtgac tgacctctct ccagtgacag tgtttgggta cctgcctgac 157740

ttcaggagtg gggtttatgt ttctacacag tgaccttttc tctcgccctc tcctccctct 157800

tgcccacaca ccagttgatt ggacctgggt tgaactcctg atccagacag gcccaagaca 157860

gttcttaatg ttaagaattt tggggccggg cacggtggct catgcctgta attgcaacac 157920

tttgggaggc cgagacaggc ggatcacttg aggtcagggg ttcgaggcca gcctggccaa 157980

catggtgaaa ccctgtcttt actaaaaata caaaaattag ctgggcatgg tggcgcacgc 158040

ctgtaatccc agctacgtgg gtggctgaga caggggaatc gcttgaacct ggaggcggag 158100

gttgtgcaat gagccgagac cgtgtcactg cattccagcc tgggtgacag agggagactc 158160

tgtctccaaa aataaaaata agaaaaagaa ttttgggcta ggtgcagtgg ctcacgcctg 158220

taattacagc attttggaag gcccaagatg ggcagatcac ttgaggacag gagttcgaga 158280

ccagcctgga caacatggtg aaactccatc tctactaaaa agacaaaagt tagccagatg 158340

tggtgatggg cacctataat cctagctcct cgggaggctg gggcaggaga atcacttgaa 158400

cccaggaagc agagattgca gtgagccaag atcacatctc tgcactccag cctgggcaac 158460

agagcaagac tctgtctcaa aaaaaaaaga atttggccag gcgcagtggt tcacgcctgt 158520

aatcccagca ctttgggagg ccaaggcagg cagatcacga ggtcaggaga tcgagattgt 158580

cctggctaac atggtgaaac cctgtctcta ctaaaaatac aaaacattag ccgggtgtgg 158640

tggtgggcac ctgtagtccc agctactagg gaggctgagg cagaggaagg atgtgaaccc 158700

aggaggcgga gcttgcagta agccaagatc gtgccactgc actacagtct gggcgacaga 158760

gtgagactcc gtctcaaaaa aaaaaagaat tttggccggg tgcggtggca catgcctgta 158820

gtcccagcac tttgggagac caaagtgggc ggattacctg aggtcaggag ttcaagacca 158880

gtccggccaa tatggcgaaa ccctgtctct tactaaaaaa aatacaaaaa ttagccaggt 158940

gtggtggcgg gcacctgggg aggctgaggc agggagaaat gcttgaaccg gggaggcaga 159000

ggttgcagta agccaagatc gtgccactgc actccagagc aagactcttt ctcaaaaaaa 159060

aaaaaaaaag aattttgcat ggggaaggag agatactgtt caccatctgg aatggtgctt 159120

ggatgtggca cttacaaaat caggagccag cactgcatgg acaaacagaa gcatgtgggc 159180

ctgagatagc aggtaccttg ataaccctga agacatcctt ggtttctgca tctattcctg 159240

catccttgca ttggactaca ttaatctgtc agttatcctt ataatgattt ttgatttttt 159300

ttttttgaga tggagtttcg ctcttgttgc ccaggctgga gtgcaatggc acgatctcgg 159360

ctcaccacaa cctccacctc ccaggttcaa gtgattctgc tgcctcagcc tcctgagtaa 159420

ctgggattac aggcatgcgc caccacacct ggctaatttt gtatttttag tagagacggg 159480

gtttctccat gttggtcagg ctggtctcga actcccaacc tcaggtgatc accctgtctc 159540

ggcctcccaa agtgctggga ttacaggcgt aagccatggt acccggtctg ttttttgatt 159600

ttttgaaacc agtctgaagt gagttttttt aattacgtga aaggagtttg gctaaaatac 159660

tgccatactg ccctaatgcc taatgattat gtattctcag catgtctgca aagtactgct 159720

gatttctgga gaataatttt tctttagtaa acttcactta agtcgtcatg tgtattctct 159780

caaaatggta tcctaaccta atggagctaa aagacacccc ttgtttttat aacaagcagt 159840

tactgaggcc caggaagggg agaagtccct ggcttgtgag atgatcacca ttagaactca 159900

ggcctgggcc agtgcctttt catgcttctc agatccttcc aaagaataat gaagattata 159960

accgctttta gcaattgtaa taaacccaga aatagaaagc tttttggtta gagtactggt 160020

agaagtttgg cgggagagat aatttttaca aaatttgtaa atacctgcca attctatata 160080

ctaggcaagg tctctggcct tgtaaaaccc ctcaaggtta caactttggt ggcccacact 160140

aatagttacc cactgaggcc ctctccgggt gaacattgag cactagagga agcccctctg 160200

cttgggcagg actgggcgtg gtgcagagta ggagcggtga tactgtggat tctgggcagg 160260

tggagatggc cagtgatgtc caataaagga cactggaggg agcagtgtga gtaaaggccc 160320

tgagggcatt catgttcagg gagggttgct gcccactggc ttgcttggca cacaggagag 160380

tgggtattcc tgccttagta actttatgta aacaagtatt tcctcagtct gttcctctca 160440

aactgcctgc tctggcacat tcagaatgtc acagaactca cctggatgca ttcagcccct 160500

tgcctaaagg tgacagtgca tctccttccc caccccaccc ctcataccac tgaagcacct 160560

gtcagactgg cccagtctgt gggcaaggag cctagagagg gcttagtttc agcttgaaag 160620

gagctgggat ttaccaagaa gcaaatgaga gacgaggatt gcaacaactg tgccatttcc 160680

ccagcttcag ctgactcctg tatattgact gtgccttcag actcatccgt aagtgacccc 160740

aggctggcct ctcccacatc acagtaagaa ttccacacac catacaactt ggaaagaggc 160800

tccagctgaa ggaagcccca cacttctttc aagtttttct tagtcttctc ttcttggcaa 160860

agagtacctt ttgtttcttc taattatgta actattggtt tagtaaatat tcacccattc 160920

agtcaccctg taagtggcag gcactgttta cagggacaca ggaaggaata aaaacttgca 160980

ggcaccttgg agcttgcatt ctattgaaga ggtaatggaa gttgggatag cagctaaact 161040

atgctggtat tggccaggcg cagtggctca cacctgtaat cccagcactt tggaggccaa 161100

ggtgggcaga tcatgaagtc aggagatcga gaccatcctg gctaacatgg tgaaaccccg 161160

tctctactaa aagtaaaaaa aaaaattagc caggtgtggt ggcgggcgcc tgtagtccca 161220

gctacttggg aggctgaggc aggagaatgg tgtgaaccca ggaggcgaag attgcagtga 161280

gccgagatgg caccactgca ctccagcctg ggtgacagag cgagactctg tctcagaaaa 161340

aaaaaatatg ctggtagttt tgattcaaga tggcctttgg agcccatgat ttaggtctcg 161400

tacccaccaa ggtctactgg aaaacatcag gctctcctgc tatagaccca tagggagagc 161460

tgcagccgag agggggagct gaagagaagt gccccttctg tgtcctgtca gcctcatcct 161520

tccgcaagga ccagttgctg tgccactcca ttcacttgct gcaagactgg aggtttttcc 161580

tcaggtgttg agcacctggt ttacaagatg tcagcatctt gatgcctgag accatcaagg 161640

caagtctctg aacagggctt accttagagt aaggcttaga agaggccgta aagtcagtct 161700

cagctccgtg gctctgcaga gctttgggac atgtgaattc ttaaaaacaa gactattgta 161760

cagttactat atgcatgcag tataaaatta taaccttgga aaatcctagc tagctgttga 161820

gctaattcca taaagtaatc agctcctgag ttctgcagtg gtaataataa tcagcataat 161880

gagtaaacac tgtgtgtgcc aggcagcgtc tcatttgatc cttgtgataa tcttgtaagt 161940

actgattttc tcccttcttt aaacaaagtt tttttttttt ttttagagag ggtctcacta 162000

tgttgcccag gctagtcttg aattc 162025

<210> SEQ ID NO 36

<211> LENGTH: 162025

<212> TYPE: DNA

<213> ORGANISM: Homo Sapien

<220> FEATURE:

<221> NAME/KEY: mutation

<222> LOCATION: 156,277

<223> OTHER INFORMATION: Nucleotide Base Change: T to C

<400> SEQUENCE: 36

gaattcctat ttcaaaagaa acaaatgggc caagtatggt ggctcatacc tgtaatccca 60

gcactttggg aggccgaggt gagtgggtca cttgaggtca ggagttccag gccagtctgg 120

ccaacatggt gaaacactgt ctctactaaa aatacaaaaa ttagccgggc gtggtggcgg 180

gcacctgtaa tcccagctac tcaggaggct gaggcaggag aattgcttga acctgggaga 240

tggaggttgc agtgagccga gatcgcgcca ctgctctcca gcctgggtgg cagagtgaga 300

ctctgtctca aaaagaaaca aagaaataaa tgaaacaatt ttgttcacat atatttcaca 360

aatttgaaat gttaaaggta ttatggtcac tgatatcctg tttcattctt tatataatca 420

ttaagtttga aatgtatact tgcactacta acacagtagt taatcttagt cctacaagtt 480

actgctttta cacaatatat tttcgtaata tgtatgcact ggtgtttatg tacgtgttta 540

tgtttatatc tgttaaaatt agcagtttcc atctttttct attttgtacc atcacatcag 600

ttcagaagga ttgacagagc aaaatgattt gatgaagtat aaaagtcaca tggtgagtgg 660

cataaataca actctgaaca attaggaggc tcactattga ctggaactaa actgcaagcc 720

agaaagacac atatcctata tgtcaagaga tgtaccaccc aggcagttaa agaagggaag 780

tacacataga aagcacaatg gtgaataatt aaaaaattgg aatttatcag acactggatt 840

catttgctcc taaagtcaga gtcctctatt gtttttttgt ttttgtgggt ttctttttaa 900

atttttttat tttttgtaga gtcggagtct cactgtgtta cccgggctgg tctagaactc 960

ctggcctcaa acaaacctcc tgcctcagct tcccaaagca ttgggattac agacatgagc 1020

cactgagccc agcccagacg ctttagcatt tatgaagctt ctgaaatagt tgtagaaacc 1080

gcataagctt tccatgtcac tttcaaagtt tgatggtctc tttagtaaac caaccaagtt 1140

attcctcaag ggcaaaataa catttctcag tgcaaaactg atgcacttca ttaccaaaag 1200

gaaaagacca caactataga ggcgtcattg aaagctgcac tcttcagagg ccaaaaaaaa 1260

aggtacaaac acatactaat ggaacattct ttagaagagc cccaaagtta atgataaaca 1320

ttttcatcaa agagaaaaga gaacaaggtg ttagcaaatt cctctatcaa ataacactaa 1380

acatcaagga acatcaatgg catgccatgt ggaagaggaa gtgctagctc atgtacaaac 1440

cagtagataa tttcaacttg ctgccgaatg aaacctcttt gcaaggtatg aatcagcact 1500

tctcatgttt gttttgcttt gttttgtttt gtttttagag acaggccctt gctctgtcac 1560

acaggctgga gtgcagtggc acgatcagag ctcactgcaa cctgaaactc ctgggctcaa 1620

gggatcctcc tgccttagcc tcccaagtag ctgggactac aggcccacca tgcccagcta 1680

attttttaaa ttttctatag agatgggatc tcactagcac ctttcatgtt tgatgttcat 1740

atacaacgac caaggtacaa tgtggaaaag ggtctcaggg atctaaagtg aaggaggacc 1800

agaaagaaaa ggggttgcta catagagtag aagaagttgc acttcatgcc agtctacaac 1860

actgctgttt tcctcagagc agagttgatg atctaaatca ggggtcccca acccccagtt 1920

catagcctgt taggaaccgg gccacacagc aggaggtgag caataggcaa gcgagcatta 1980

ccacctgggc ttcacctccc gtcagatcag tgatgtcatt agattctcat aggaccatga 2040

accctattgt gaactgagca tgcaagggat gtaggttttc cgctctttat gagactctaa 2100

tgccggaaga tctgtcactg tcttccatca ccctgagatg ggaacatcta gttgcaggaa 2160

aacaacctca gggctcccat tgattctata ttacagtgag ttgtatcatt atttcattct 2220

atattacaat gtaataataa tagaaataaa ggcacaatag gccaggcgtg gtggctcaca 2280

cctgtaatcc cagcacttcg ggaggccaag gcaggcggat cacgaggtca ggagatcgag 2340

accatcctgg ctaaaacggt gaaaccccgt ctactaaaaa ttcaaaaaaa aattagccgg 2400

gtgtggtggt gggcacctgt agtcccagct actcgagagg ctgaggcagg agaatggtgt 2460

gaacctggga ggcagagctt gaggtaagcc gagatcacgc cactgcactc cagcctgggc 2520

gacagagcga tactctgtct caaaaaaaaa aaaaaaaaaa aaagaaataa agtgaacaat 2580

aaatgtaatg tggctgaatc attccaaaac aatcccccca ccccagttca cggaaaaatt 2640

ctcccacaaa accagtccct ggtgccaaaa aggttgggga ccgctaatct aaataatcta 2700

atcttcattc aatgctaaaa aatgaataaa ctttttttta aatacacggt ctcactttgt 2760

tgcccaggct ggagtacggt ggcatgatca cagctcactg tagcctcaat cacccaggcc 2820

ccagcgatcc tcccacctaa acttcctgag tagctgggac tacaggcacg caccaccatg 2880

cccagctaat ttttaaattt tttatagaga tgggggtctc accatgttgc ccagactggt 2940

ctcaaaccct gggctcaagt gatcctccct caaactcctg gactcaagtg atcctccttc 3000

cttggcctcc caaagtgctg ggattacaag catgagccac tgtacccagc tggataaaca 3060

ttttaagtcg cactacagtc atggacaatc aggcttttca acatgcagta tggacagtga 3120

gtcccagggt ctgcttttcc atactgaaat acatgtgata ctaaggagaa aggtgctcgc 3180

aaggatattt aaaatgaaga atatttaaaa tgaggaaaaa actgtttctt catgactttg 3240

ataaggctga taaagaccat ttctgtgatc tcaggtgatt cactcaagta gtatatttca 3300

gtaatcatta tctggaacag cctgaatctt aaccaaaata ccatgatttt ttaatgctgt 3360

tatgatacct tgatgatatg accaaactgc aatgtaggca gctaaatctc cacgagtttg 3420

acttccccga gagttgacag ttttcttcac aaattaaaga aatatatttt ttgatacatg 3480

attggcatat ttaaaaacta cactgaaatg ctgcaaaatg atataaagaa acattttcca 3540

gaatcaaatg caatcaaaga gtggattagg aatctactca ccattatcaa ctaaatagaa 3600

acacttggac tgggtgtggt ggctcacatc tgtaatctca gcactttggg aggccaaggc 3660

aggtggattg cttgaggcca ggagctcaag accagcctga gcaacatagc aaaactctgt 3720

ctctacaaaa aaaaaaaaaa attaaccagg catggtggca gatgcttgta atcccagcta 3780

ctctggaagc tgaagtagga ggactgcttg agcccaggag atcaagactg cagtgagccg 3840

tggtcatgct gcgccacagc ctgagtgaca gagagagacc ctgtctcaaa aacaaaaaca 3900

aacaaaaaac acttaacctt cctgtttttt gctgttgttg ttgttgtttg tttgttttga 3960

gatggagtct cactctgttg cccaggctgg agtgcagtgg cgtgatcttg gctcactgca 4020

agctctgcct cccgggttca cgccattctc ctgcctcagc ctcccgagta gctgggacta 4080

taggcgcccg ccaccacgcc cggctacttt tttgcatttt tagtagagat ggggtttcac 4140

cgtgttagcc aggatggtct tgatctcctg acctcgtgat ccacctgcct cggcctccca 4200

aagtgctggg attacaggca tgagccaccg cacccggcca acctttctgt tttttagttt 4260

gatatgcttg ttaactcagc agctgaaaga atgctgaaag tggccttcag taaaaaaatt 4320

tcactagaat ctctacatcc atatttaatc tgaatgcata tccagattga tcagttagag 4380

caaaaacact catcatcatt cctgatgacc tctaattctg gtttcggctt tctatttcaa 4440

tggaaacaga ataaggaaag aaatggaagg gctctggaaa tttgtcctgg gctatagata 4500

ctatcaaaga tcaccaacaa taagatctct cctataaata taaaacaagt ataattaatt 4560

ttttaattat ttttttctct tcagaggatt ttatttcaag ataaaacata acttctaccc 4620

atactattga ttccaaaggt tagaaaaagt gtttttcctc atcttatcct tcaaagaggt 4680

cacagcaatg caaacatcta taaaatgcct ctgcataatt gtcagaagct atagtccaga 4740

aatcattgaa aatgcttttc cattttaagc ttaggtgagg tgtcttagga aacctctatg 4800

acaacttact ctatttattg ggaggtaaac tcccagactc tcccagggtc tcctgtattg 4860

atctcatttt ttaggcttcc taatcccttg aagcacaatc gaaaaagccc tggatctctt 4920

ttctgcacat atcatcgcgg aattcattcg gcttccagca agctgacact ccatgataca 4980

agcggcctcg cccttctccg gacgccagtc cttgctgcgg ttagctagga tgaggggttt 5040

gctgggcttc agtgcaggct tctgcgggtt cccaagccgc accaggtggc ctcacaggct 5100

ggatgtcacc attgcacact gagctcctgg caggctgtac caatttttta attatttaat 5160

atttattttt aaaattatgg tgaatatttt ggtattctgc tctaaaatag gcccataaat 5220

gcacagcaga tatctcttgg aacccacagc tttccactgg aagaactaag tatttttctt 5280

ttaaagatgc tactaagtct ctgaaaagtc cagatcctct acctctttcc atcccaaact 5340

aagacttgga atttatgaga gatctagcta acagaaatcc cagacacatc attggttctt 5400

cccagagtgc agtcctccta aagaggctca gccctaagca ggcccctgca ccaggagggt 5460

gggtctgaga cccacatagc acttcccaag gtgcatgctc cagagaggca ctgaaacagc 5520

tgagcacaag cctgcaagcc tggagaactc tcacagtcag aacggagggg gcccagtggg 5580

actaacataa agagaaaagg gaacacagag aaatggatgg caccaacaac cagcaaagcc 5640

ttcatggcca atgaaagcat cagtgacggg gccagaaccc tcatccccaa agactcttca 5700

ctgcctttag tgaaaaacaa tggctagaga gtgaagttat gatcatgtat agagaggtaa 5760

agttacattt ttatattctg actctgctaa tgtgaaattc cctatctgct agactaaaag 5820

tttcagacac cctgttcaaa tatcccatta gttgctagag acttaaaatg aacagaacgc 5880

acattgtcag gatgactatt accaaaaaat caaaagacag caagtattgg tgaggatgta 5940

gagaaactgg aacttttgtg cactgtttat gagaatgtaa aatggagcag ctgctgtgga 6000

aaagagtatg caggttcctc aaagagtaaa accaagatgt ggaaacaact aaatgcccat 6060

cagtggatga aggggtagac aatatgtggt atatacatac catggagtac tattcagcct 6120

ctaaaaaaaa aaaaggaaat tctataacat gcaacagcat ggatgaatct tgaggacatt 6180

ttgctaatga aataaggcag tcatagaaag acaaatactg cacgactcca cttatatgag 6240

ataccaaaaa tagacaaatt catagaatca aagagtacaa tggaggttac ctggagctgc 6300

agggcgggaa acgaggagtt actaatcaac gaacataacg ttgcagttaa gtaagatgaa 6360

taagctctca agatcagctg tacaacactg tacctagagt caacaataat gtattgtaca 6420

cttaaaaatt tgttaagggt agattaacaa atgtagtaga tccacaaatg tggttaagtg 6480

ttcttaccac agtaaaataa aaaaagaata tcaagcccag gagttcgaga ctagcctggg 6540

taacatggtg aaaccctgtc tctacagaaa atacaaaaat tagccagctg tggaggtgca 6600

ctcctaggga ggctgaggtg ggaggcttgc ttgagcccag gaggtcaagg ctgcagtgag 6660

ccatgattgc accactgtac tccagcccag atgacagagc aagacaccac cccccccaaa 6720

aaaagaaaaa gaatatcaaa cattttaaaa gatcagatac gcaagaacaa caacaaaaaa 6780

gagatgaaca gagcatcgac cctcatctag tgggattctt ggtctaactg aaaaacagac 6840

attgagagac aaacaatgac agtgatgtga tcacagcaat tacacaggta tcccctgggg 6900

actgcagaag aaaggaggaa tgcctaactt tcagaaaata gagaaagcgt caaacagttg 6960

gtgaaagcct tccaaaacta gagagaactg cacacaccaa atcacagaaa gaagaaaagc 7020

cgtgggagat tctgggaccc accggctatt tttgatggct gaacaccctg ctgcaggaga 7080

gacaggagct ggaaagcatg gtgggatgaa acctcaaaca gctttgcctg cattgcttaa 7140

gatgactggg cttgattaac tctagtcaat ggggacaatt caatcaaaga agaaagatgc 7200

tcaaattcac attttagaat gattttttat ggcagtatgg ggaatagatt aaaagagagt 7260

gaagctggag gcaagaaact tgttaagagg caactgaaac agtctagatg ataaataata 7320

aactgacaga gtgactagaa aaatcagaac aggctgaatc aacagatacc tagatgaaaa 7380

taacaggact tgatcaccag ttgtatcttg gagaggaagg agttgtttcc ttgctttccc 7440

tacgactggg aatacggaag gtttgccgtg tgtattggtt atatactggt gtgtagccaa 7500

tcactgacaa ccatttagca gcttaaaaca caaaggctta tctcccagtt tctgtgggcc 7560

aggaatctaa gataggctta gctggctggt tctggctcag agtttctcaa gaggttgcaa 7620

tcaagatgtc agctggggtt gcatcatctg aaggctcaac tggggccgga gggtccactt 7680

ccaaggagtt cactcacctg cctgacaagg cagtgctggt tgttggcagg agatctcaat 7740

tcattgccaa gtgagcctct ctatagcatt gctggaacat cctccccatc tggcagttgg 7800

cttctctcag catgagtgat ctgagagaga gagcaaggag gaagccacag tgttcttcct 7860

actcctactc ctaacactat ggacctactc ctaacactct cacttctgcc ttattccatt 7920

agttagaaag ggaactaagc tccacctctt gaaataagaa gtgtcaaaga atttgtggat 7980

atatttaaaa atcatcacac tgtggaagtg gatagggggt tcaattaatg ctgaacttga 8040

aatgcctgag acattcaaat gtccaacagg caatgaacat acccatagat ggtcatgact 8100

ttagcaagaa tagaggaaga tcacagaatt aaggaggaat tgaaaggtaa aagaagtgga 8160

gtcagattcc ccctgaaaag tgagccatga aaggaacttt aactattgag ttagaggtca 8220

gagtaggaaa tttcggtgga attctttttt aaagaaagga accatataag catgttttga 8280

ggtagaggga gaataaatca gtagacaggg agaggtaaaa aacataaatg ataggggata 8340

gttgacaaag gtcttggcag aatcccttac ccattgactt ggggccaaga gagggacact 8400

tctttgtttg agggataagg aaaataagaa agaatgggtg ctatttagtg tggtcctgtc 8460

tctagggcaa acgcataggt aacaaactgt gtgtgttagg aatatagatg tgacctcaca 8520

ttgagattct cacctcaaat ccattttgtt gttacctgta ccttcctacc ttctcttttt 8580

gctacatgca gactgctgtt ttgtcttcct ggcctgttcc aggtttcagc attctggcat 8640

atctgctacc ctgttcccaa acctctctag agtccatgct ccttccttgg atagtgtttg 8700

attgggccac gtatctaaga agtgatgcct tcagttaggc ctgagaacct cctctatgga 8760

aatctccatc agtgaccctg acagacttgg tatcttggag atgtcactgc tcccagcctg 8820

tggtctagga gaatctcagc ctgggcctct agtagtatgg ataaggcgtt aaggtatctt 8880

tgaaccagag tctgtcatat tcctcaatgt gggacagata aaacagtggt agtgctggtg 8940

tttctgagct agaactctgg tttttggtct agattctttg atgtatgacc tttcagaggt 9000

attaaaattt gttctaatac aatgttcaat acaaatgtag ttccttttct gttaggacct 9060

caacaaaaca tgaccaactg tagatgaaca ttaaactatg acaattcatg gaaatgaata 9120

cagtaatacc tgcggttccc ccattttagc agtcactatg gtgacatttg gcacaaatgg 9180

ctatttaagg gtgcttttgt taaaacctac catcttacta ggcacatgat attgaaacta 9240

atgaaataat ggagaaactt cttaaaaact tttaatgaat aaagtgatga agtgataata 9300

ttttagctgc tatttataaa gtgactatta caggtcaaac attcttctag ggtttttttg 9360

ttgaagttgt cacatttaat ccttaataac ccactatgag tcaggtattc ttctctcccc 9420

tttggacagt tggggaaatg ggggtcagag aggttaggta atttgctcag ggccacacaa 9480

cctgcatgta gaaaatctga gatttgtaca ggaacgtatc aaactctgaa gtccatgctt 9540

ctattttccc atgctgcctt tctaataaaa ggtaactaat gctactggat gctgccccca 9600

aagtgagtca ctttcacccc accctacttg attttctcca taaaactaat cacatcctga 9660

caacttattt attgctgatc tcccccacta gattataaac tcaataaaag caagatcctt 9720

gtctgctgaa tatcagtacc taaaacgctg tctagcacag agcaagtaat taatatttgt 9780

tgaatgaaca aataaaggaa aaaaattcaa aggaagaaaa agccctaaaa cagatgttta 9840

cctaaacata cattttaaaa gaaagcatat aacaaattca ggacagaatt taaatttgat 9900

tttttaaaga aataaccaag tgctagctgg gcacagtggc tcacacctgt aatcctagca 9960

ctctgggagg ccgaggcagg cagatcactt gaggtcaaga gttcaagacc agcctggcca 10020

acatggtgaa acctgtctct actaaaaata cagaaattat ccaggcatgg tggcaggtcc 10080

ctgtaacccc agctactcag gaggctgagt caggagaatt gcttgaaccc aggaggcaga 10140

ggttgcagtg ggccaagatt gcaccactgc actccagcct gagtaacaaa gcaagactct 10200

gtctgaagga gaaggaaaga aagaaggaaa gaaggaaaga aggaaagaag gaaagaagga 10260

aagaaagaaa gaaagaaaga aagaaagaaa gaaagaaaga aagaaagaaa gaaagaaaga 10320

aagaaagaaa aagaaagaaa gaaagaaaga accaagtgct tatttgggac ctactatgct 10380

atgtttttcc atgcacgcta ttttcagtaa agcagttagc aaacttgcaa gatcataaca 10440

acaaatatat gcttctataa ctctaaaatt gtgctttaag aagttcctct ttaccagctc 10500

atgtatgcat tagttttcta agagttacta gtaacttttt ccctggagaa tatccacagc 10560

cagtttattt aaccaaagga ggatgcttac taacatgaag ttatcaaatg tgagcctaag 10620

ttgggccagt tcatgttaat atactccaga acaaaaacca tcctactgtc ctctgacaat 10680

tttacctgaa aattcatttt ccacattacc aaggagccag ggtaggagaa tatagaaaga 10740

ccacccaaga atccttactt ctttcagcaa aatcaattca aagtaggtaa ctaaacacat 10800

gccctaacaa tgaatagcag attgtgctca gaagaatgat ctacaacatc ttactgtgaa 10860

ggaactactg aaatattcca ataagacttc tctccaaaat gattttattg aatttgcatt 10920

ttaaaaaata ttttaagcct aaattttaaa aggtttgata ttggtacatg aatagacaaa 10980

cagacatgga ctagaccaag aattaggttc aaacatatac aggaatttaa tatacgataa 11040

atctagtatt ccaaaggaac caacaaatgg tgttcagaca gcaggatagg catcaggaaa 11100

aacacagttg ggcaccctac cttactccta acaccaggag taactgaagg agcaccaaat 11160

atttatttat tttaattata gttttaagtt ctagggtacg tgtgcacaac atgcaggttt 11220

attacatagg tatacatgtg ccatgttggt gaggagcacc aaatatttaa aagaaaaaaa 11280

ttggccaggg gcggtggctc acacctgtaa tcccagcact ttgggaggcc aaggtgggca 11340

gatcacctga ggtcgggagt tcgagaccag cctgagcaac atggagaaac cccatctcta 11400

ctaaaaatac aaaattagcc aggcatggtg gcacatgcct gtaatcccag ctacttggga 11460

ggctgaggca ggagaatagc tttaatctgg gaggcacagg ttgcggtgag ctgagatatt 11520

gcactccagc ctgggcaaca agagcaaaac ttcaactcaa aaaaattaat aaataaataa 11580

aaataaagaa agaaaagaaa aaaatgaaaa tagtataatt agcagaagaa aacaccgtag 11640

aatcctcgga ctcttaggat ggggaatgcc tataatataa aaaccctgaa gttataaaag 11700

agaaaatcac ctacatacaa accaaatctt tctacatgcc taaaacatag cacaaacaca 11760

gctaaataat catagctgaa tgaactggga aaacaaaact tgactcatat ccagacagag 11820

ttaattttcc tacacataaa gagtacctat ataaacccaa caaaaaaacc accactaacc 11880

caaaataaaa atgtgacagg taatgaacag gtagttcaca gagaatacaa atggctcttc 11940

ggcacataag atgctcagac tgacttttac ttatttattt tttgagagac agggtctcac 12000

gatgttgccc aggttaggct caaactcctg ggctcaaatg atagtaccag gactacaggt 12060

gtgccccacc gcacctggct cctcaaccac ctgtattaac aggaaatgca aaataaaact 12120

ttcaaatcta ttttacctat tagaatggca aaaatttgaa aaacttcaaa catcatcatg 12180

ttggtgagaa tgtgaggaga ctggcactct cattttttgc tgatagcata tatatactga 12240

tggcttctat ggaaagcaat ctggcagcgt ctatcaaatg tacaagtgca tatatccttt 12300

gacaaagcaa ttccactcta ggaatgtgtt ctatatggtt gtgcttcctg gggctgggaa 12360

ctgggagcta agggacaggg gcagaagata atcttctttt ccctccttcc ccgttaaaca 12420

tgttgaattt tatatactgt aatatattat ttttcacaaa agataatttt taagcgatat 12480

gtctgggaat tttttttttt cttttctgag acagggtctc actctgtcat ccaggctgga 12540

atgccatggt atgatctcag ctgactgcag cctcgacctc ctgggttcaa gcaatcctcc 12600

cacctcagcc tcctgagtag ctgggactac aggcacgtgc catcatgcta atttttgtat 12660

atacagggtc tcactatgtt gcccaggcta atgtcaaact cctaggctca agcaatccac 12720

ccacctcagg ctccaaagtg ctgggattac aggcgtgagc caccgcgcct ggccctggga 12780

attcttacaa aagaaaaaat atctactctc cccttctatt aaagtcaaaa cagagaagga 12840

aattcaacct ataatgaaag tagagaaggg cctcaaccct gagcaacaaa cacaaaggct 12900

atttctgaga caggaatttg ctgaacaaaa tcgagggaag atgacaagaa tcaagactca 12960

cttctcggct gggcgcagtg gctcacacct gtaatcccag cactttggga ggccgaggcg 13020

gacagatcac gaggtcagga gattgagacc atactggcta acacagtgaa acccagtctc 13080

tactaaaaat acaaaaaatt agccgggcgt ggtggcaggt gcctgtagtc ccagctactt 13140

gggaagctga ggcaggagaa tggcgtgaac ccaggaagcg gagcttgcag tgagccgaga 13200

tcacgccact gcactccagc ctgggtgaca gagcaagact ctgtctcaaa aaaaaaaaaa 13260

aagactcatt tctctagatc ttgagccgta ttcaaattta tctcagctta gtgagaggtt 13320

aaagcaagga atatccttcc ctgtgggccc tgctccttac tgaaggaagg taacggatga 13380

gtcaaggaca ccaatggaga aaagcactaa caccattatc tgatgaacat tacgtgaaga 13440

agggtaagaa gtgaagtgga attgctgaag aagtcagtga aagcggacat tcatttgggg 13500

aaatggaata taggaaatcc ataaaagtga ttaaaaagat gttagaggct gaggcggggg 13560

gaccacaggg tcaggagatc gagaccatcc tggctaacac ggtgaaaccc catctctact 13620

aaaaatacaa aaaattagcc aggcgtggtg gcaggcacct gtagtcccaa ctactcggga 13680

gactgaggca ggagaatggc atgaacctgg gagacggagc ttgcagtgag ccgagatcac 13740

gccactgcac tccagcctgg gtgacagagt gagactccat ctcaaaaaaa aaagttagat 13800

acgagagata aagatccaac agacacacaa ctgctaattc tgaacagaac aaaacaaatg 13860

gcacaggaaa agaaaattta agatataaca ccggaaaact ttcctgaaat tgagtaactg 13920

aatctatagc ttgaaagggt ttagcatatg ccaagaaaaa tcagtagagt ccaaccagca 13980

caagacacat ctagcaaggc tggtgattct accaacacag agaaagaagt gggtgaccca 14040

taatgcggaa aaaggcagac catctgcagt cttctccaga acactggagt ctgaagacaa 14100

aagaatgctg cctactgagc cagaagggag agaaagtgac ccaacacatc tttaccaagt 14160

tagaatgtca cgcattattt aaaggctgca aaagccatga aagacatgaa agaacacaag 14220

catttacaac atgaaagaac acaagcattc tcatactcaa gaatccttaa gaaaaatgta 14280

gtcctaatcc agcccactga aagttaaatg tacttaatgt gctcattaat gggaacttca 14340

tagcttcaaa tcagtctggt cccatctacc aacatctctc gcccggcttt cctgcaatag 14400

tcagcacctt tccctcctcc cagtcttgtc ccctggagtc tgctctcagc atagcagagt 14460

gaccacatca acacccaagt cagagccctc cagtgcgcac tggtctacaa agcccttccc 14520

accccccacc ccacgtgccc tccggatcct tgtgacgtgt ctcctgcata ccctagcagc 14580

cctggcctcc tcactgcccc tcctgtacat caggaaggcg actccttgag tcttggctct 14640

ggccgcctcc tccacctgca gtgagttaac tcccttacct actctaggtc attgctcaaa 14700

tgtcagcatc tcaatggggc cctccctgac taccctattt aaattctaca tactcccctt 14760

gaccccatgg acctcactca ccctattcca cttttattct tacaatttag cacttgttct 14820

cttctaacgt attctaagac ttactcattt attacattgt ttgccacccc ctctagtaca 14880

taaactccag aggggcaggg atttctgtct atttattcat ttctttatcc ctaggacata 14940

gaacagggca tagttcagag tattcaatgt tatcaatgaa tgaactagca gtagtaccag 15000

ttccagttag gcacagaatt aaatctaaat agaattaaat ctcatggtct gggttaacta 15060

tggatagaaa attagatata attttaagaa gcctagaaag aaaaaattaa taatgtaaaa 15120

ataatattaa tttgataata ataacaaaaa ctctgccagg cactgtggct caaatctgca 15180

atcccagcta ctcaggaggc tgaggtggaa ggatcacttg agaccagagt tcaagactca 15240

gcctaggcaa cacggcaaga aactgtctct aaaaaaatta aaacttaaat ttttaaaaaa 15300

gaattctcaa agcgtcacaa aaactggaga ttaaggtaca ggaagtgtga agtaatatta 15360

ctatgctaat ggtttttttt ttttttagaa aggtataacc aaaagatttc tttctcaagt 15420

cgataaactg agaaagataa gcatatcttc caattaacag agggggagga aaagccagat 15480

acaacaaaat aagatataaa ttagtttcca gttgaaaaca agagtaggag ttattttgca 15540

tcacctcacc tgtgacctcc cccagcccaa aaaacactac tgataaacag ggtagaaaag 15600

catcatctca gataaagcag gaaaaactgc cacagtctca aaccacaaac tataagcaca 15660

cacctggcca accctgccaa gtctgggctc agtaggagga acgtgctgag agctaggatg 15720

taccaactta gacattctgt gggatacaga tgtccctgga agggtcacac catctcaaag 15780

gcacctgtaa tgcccactga ttacagccac catatgtgag agagaaactc agggcactta 15840

gagagtataa caagaacctt atgtcatctg agatgaggaa tcctcagccc tgcaaattaa 15900

ccaactcttt agaacaactg gcaaaacata aatatccaca acttttgttt cagtaattcc 15960

actcttagat atcaatccaa agtacatgag acagcagata cacacacaaa atggtattta 16020

ctgcagcatt gtttataata gcaaaaaaca agaaataatc catatgtctc aataggatac 16080

tgggtacatg agggtatgta cccatcattc aaccatcaaa aagagtgata tggatgtcca 16140

cagatggaca taaaaagctg tgtgttacgt gaaaacaaac tcaagcagca gcaggatggg 16200

cttatgatag tcagtatgag ctaatttctg gaaaaaaaaa tctagtgtgt gcacagaaaa 16260

catctgaaag aacagaaaca aaactatcag cagaatattg agatgtttta ctaagttgta 16320

tatctatact gcttgtaatt tttaccccaa gcaagaatta ctttttggaa aaagaaaatt 16380

caggaaataa agcatttctt taaacttcat gtttaaacaa atggtgatgg aataaaagag 16440

ttcttattca tcataaacac acacagcaca catgcacgca tgtgcgtgag cacacccttt 16500

acttgataaa taccatgttg aatattttag tctttccttt taggttctat cccttcactc 16560

aaaatgcggt tataaataaa tgtacttttc atgtgccttc tgcctaaacc cactttaata 16620

taactttaca gtcccattat cattatagtc tcaaagctag actcagcctg aaactaccct 16680

ttcatttgga acccttatta aaatgccaca tacagctcct tcaaataaaa acaaacccta 16740

ggacctgaca ctaggcttcc tttgttgcta ctcataatgg ccaagttctg tgcttataat 16800

acatcttctt tcattttatt gctacatatc caagggtttt atatgttttt cttattatat 16860

cttaattcaa aacaccatca cgctcttttc cagatgaaaa taaggaaaag aaattgagca 16920

actgactgac ttaaaggtca taaaactata tagtagcaga gtcagcaaaa gaagaaacac 16980

acatctccca agtagaggct gaaaaccagt accattcacc tccagggtga gctatataca 17040

gattacaaag tcaccttctc taaatgttca aactgaatcc catacccata ctttaccact 17100

acctcgtaag aacagcctca gatcttgtta tagccttttt tttagcatgc tgaagccaat 17160

aaaatgcttc ccattcagca agagaaacaa gttctgaaac actgaataat ctgcccaggg 17220

cctatgaaca tttccactgt gagaaatgtt ctccactgtg tggagaagat ccttactctt 17280

ctccacacag gcagaacatt agaaaaattc ttggattcta tgatgcacag cttaggagtc 17340

tgtttagcac aatttaagtc caaatagtta ttaaatcctc ctctgttcca gaaacagtgc 17400

taaatactgt gaatataaaa attgaaaaga tactctcctg gctcccaaga aagtcagcca 17460

gatagaggag acacaggcac acaaatcact gtcacatgaa gctctacctc cctaacttca 17520

aacgagggcc taagtcacca agaatacagt agcagttgtg actacgagta actactataa 17580

ttcaatactt tatcttccct tagaaaactc ttctcccttg gaaatttatt tgcatttcta 17640

aataccattc cttactaaaa ggaagcaggg ctccttgggg aaatagctga ttctaggtgt 17700

ggactatgaa atgaaaatgg tgagtctggg acatcccatg ttgcccagaa atcaaggaac 17760

tgcccaaaga ttaacagagt catgttaaat ggacctaaga gtgaaccaga aggagctcac 17820

tttgccccgc gtggaacaat ttcaagaaaa acatgacagt aatgaattat aaaacatgaa 17880

ttaaaataca tattggtact aaaaagagaa caaaaggatg tggctttgga taaagctctt 17940

cttcatggaa gaataccagc taataaatgt aaaggaaatg agagaattag aaaaattatc 18000

attttgtaaa ccttaatata ttcacctaga catgctaaaa ccactgagta aaaggctgct 18060

tgggaagagg atgctcacat gatctcagag tttcacacca cagataattt attagataca 18120

ggaaggaaga tgtgatcaag cttcctgtga cccccagcca ggccccacaa cactatgtgc 18180

ctccttgtga tgtgggagct acacagcatc gcccacacag cttctcgcca aaactgtttg 18240

aagctaatca caagggaaga actggacagc ttctgaccat gagacgctcc accagacaac 18300

ttgcttggcc tctccaaaga aacttgcttg gcctctccaa agaaaactca gtttcattta 18360

aaaacaaaac taattattta aaaacaaacg aaaagcaagt tgtggacttg agctccaggg 18420

acagagcaga catacttttc cctgttcttc ccagtaagtg gtaataaaaa ccctcaacac 18480

tagatataaa acaaatataa gaaggttctg gaaggggaag aggaggcaga ctatccaggt 18540

gccttgaggc ccacagaaca acccagtgat gggttcactg ggtcttcttt ttgcttcatt 18600

atctcagact tggagctgaa gcagcaggca acttcaaaac accaaggggc acagattgaa 18660

aagccccaag aaaagcctgc cctctctagc caaaggacca ggaaggagac agtctaatga 18720

gatggaacac atttagacag taactgccca tttaccagca ataactgagc agggagccta 18780

gacttccagt cttgtgagga cgtaccaagg tacccaacac ccccaccaag gctgagtaag 18840

gactgcgact tttatccctg catggcagta gtaaggagcc catccctcac ccgccagcag 18900

tgtcagggga acctggactt ccactcccac ccaggagtga tgaggccctc cctgctgggg 18960

tcatgtcaga ggaggcctag tggagattca gtgacttaac cttttcccag agataatgag 19020

gccacctttc ctccctcttc ccccatggtg acagtgaaag cactgtggca agcagtaggc 19080

actcctaccc ctcctagcca gggaggtatc agggaggcca agtagggaac cagaataccc 19140

acaaccaccc agcagcaaca ggggtccccc accccattgg gtgtcaatgg aagcagagcg 19200

gaaagcctgg atatttaccc ccatctagaa gtaacaagct gatgtccccc ttcttctact 19260

acaatggtgt tcaaaacagg tttaaataag gtctagagtc tgataacgta atacccaaat 19320

cgttgaagtt ttcattgagg atcatttata ccaagagtca ggaagatccc aaactgaaag 19380

agagaaaaga caattgacag acactagcac taagagagca cagatattag aactacctga 19440

aaggatgtta aagcacatat cataagcctc aacaggctgg gcgcggtggc tcacgcctgt 19500

aaccccagca ctttgggagg ccgaggcagg tggatcacaa gatcaggaga tcgagaccat 19560

cctggctaac acggtgaaac cccgtctcta ctaaaaatac aaaaaaaaat agcaaggcat 19620

ggtggtgggc acctgtagtc ccagctactc gggagcctga ggcaggagaa tggcatgaac 19680

ctgggaagag gagcagtgag ccgagatcgc accaccgcac tccagcctgg gcaacagagc 19740

aagacttcgt cccaaaaaaa aaaaaaaaaa aaaaaaaagc ctcaacaaac aactacaaac 19800

gtgcttgaaa caaatgaaaa aaaaatcttg gcaaagaaat aaaagatata tattttggcc 19860

aggtgcagtg gctcacagcc tgtaatccct gcactttggg aggctgaggc aggcggatca 19920

cctgaggtca ggagtttgag accagcctga ccaacatgga gaaaccccgt ctctactaaa 19980

aatacaaaat tagccagtca tggtggcaca tgcctgtaat cctagctact caggaggccg 20040

aggcaggaga atcgcttgaa ctcaggaggt ggaggttgcg gtgagccgag atcccgccat 20100

tgcacattgc actccagcct gggcaacaag agcaaaactc catctcaaaa aaatagatac 20160

atattttaat ggaaatttta gaattgaaaa atacagtaac caaattgaat ggaaagacaa 20220

catagaatgg agggggcaga caaaataatc agtgaacttc aacagaaaat aatagaaatt 20280

acccaatatg aagaacagaa agaaaataga ctggccaaaa aataaagaag aaaaaagagg 20340

agcagcagga ggaatgatgg aaaaagagaa aggaaggaag gaagggaagg agggagggaa 20400

ggagtgaggg agaaagtctc aaagacctct gagactaaaa taaaagatct aacacttgtc 20460

atcagggtcc aggaaagaga caaagatggc acagctggaa acgtattcaa aaaataatag 20520

ctgaaaactt cccaaatttg gcaagagaca taaacctata gattcgaaat gctgaacccc 20580

aaataaaaag cccaataaaa tccacaccaa aatacatcat agtcaaactt ctgaaaagac 20640

gaaaagagaa aacgtcttga aagcagtgag tgaaacaaca cttcatgtat aagggaaaaa 20700

caattcaagt aacagatttc ttacagaaat taaggaagcc agaaggaaat gacacaatgg 20760

ttttcaagtg ctgaaagaaa agaagtgtca acacaaaatt ctagattcag taaaaatatc 20820

cttcaagaat caatgggaaa tcaagacagt ctcagataaa gcaaaataag agaatatgtt 20880

gccagcagat ctcccctaaa ggaatggcaa aaggaagatc atgcaacaga ccaaaaaatg 20940

atgaaagaag gaatccagaa acatcaagaa gaaagaaata acatagtaag caaaaataca 21000

tgtaattaca ataaaatttc tatctcctct taagacttct aaattatatt gatggttgaa 21060

gcaaaaatta taaccctgtc tgaagtgctt ctactaaatg tatgcagaga attataaatg 21120

gggaaagtat aggtttctat acctcattga agtggtaaaa tgacaacact gtgaaaagtt 21180

acatacacac acacacgtaa gtatatataa atatatgtgt gtatatgtgt gtgtatatat 21240

atatatacat ataatgtaat acagcaacca ctaacaacac tatacaaaga gataataacc 21300

aaaaacaatt tagataaatt gaaatggaat tctaaaaaat attcaaatac tctacaggaa 21360

gacaagacaa aaagagaaaa aaagaggagg acaaactaaa ttttttaaaa acataaataa 21420

aatggtagac ttaagcccta acttatcaat aattacataa atgtaaatga tctaattata 21480

tcaattaaaa gacagagata gcagagttaa tttaaaaaca tagctataag aaacctgctt 21540

tgggctgagt gcagtgactc acacttgtaa tcccagcact tcgggaggcc aaggcgggtg 21600

gatcacctga ggtcaggagt tccagaccag cctggacaac atggtaatac cccatctcta 21660

ctaaaaatac aaaaaaatta gccaggcatg gtggcacacg cctgtagtcc caactactca 21720

ggaggctgcg acacaagaac tgcttgaacc cgggcagcag aggtagcagt gggccaagat 21780

tgcgccactc cagcctgaac gacagagtga gactccacct cagttgaaaa acaaaaaaga 21840

aacctgcttt aaatatacca acatatgttg gttgaaatta aaagaataaa atatatcatg 21900

aaaacattaa tcaaaagaaa ggagtggcta tattaataac ataaaataga cttcagagaa 21960

aagaaaattt caagagacag gaataaaagg atcaagaaaa gatcctgaaa gaaaagcagg 22020

caaatcaatc attctgcttg gagattcaac accctctctt aacaactgat agaacaacta 22080

gacaaaaaaa tcagcatgga gttgagaaga acttaacacc actgaacaac aggatctaat 22140

agacatttac ggaacactct acccaacaat agcaaaataa acattctttt caagtattca 22200

ctgaacatat ccttagaccc taccctgggc cataaaacaa agctcactag tgattgccga 22260

aggcttggat ggacagtgga agagctgcat ggggagggag aaggtgacag ttaaagagtg 22320

taggatttct ttttgggata atgaaaatgt tccaaaattg attgtggtga tgttggcgca 22380

actctacaaa tataaaaaag gccattgaat tgtacgtttt aagtgggtga aacatatggt 22440

atgtggatta tatctaacgc tttttaaaaa cttaacacat ttcaaagaat agaagtcata 22500

cagagtgtgc tctactggaa tcaaactaga aagaggtaac tggaggataa cgagaaaagc 22560

ctccaaatac ttgaaaactg gacagcacat ttctaaaatc atccgtgggt caaagatatt 22620

catttctgat attcattttt attgtttaat gtatttttaa aaatttctta agggaaataa 22680

actgactaaa aatgaatatg gctgggtgcg gtggctcacg cctgtgatcc cagcactttg 22740

ggaggccgag gctggtggat cacaagatca ggagttcgag accagcctgg ccaagatggt 22800

gaaaccccgt ctcaactaaa aaactacaaa aagtagccaa gcgcagtggc gggagcctgt 22860

ggtcccagct acttgggagg ctgaggtagg agaatcgctt gaacacaggc agcagaggtt 22920

gcagtgagcc aagattgtgc cactgcacgc cagcctgggc gacagagact gcctcaaaaa 22980

aaaaaaaaaa aaaaagaata tcaaaatttg tgggacatag ttaaagcaat gctgagaggg 23040

aaatttataa cactaaatgt ttacattaga aaagagaaaa agtttcaaat caatagtctc 23100

cactcccatc tcaagaacac agaagatgaa gagcaaaata aacccaaagc aagcaaaaga 23160

aagaaaatat aaaaataaat cagtaaaatt gaaaacagaa acacaataaa gaaaatcagt 23220

gaaacaaagt actgattctt cgaaagatta ataaaattga caaacctcta gcaaggctaa 23280

caaacaaaaa agaaagaaga cacggattac cagttattag aatgaaagca taattagaaa 23340

caactctaca cattataaat ttgacaatgt agatgaaatg gactaattac tgaaaaaaca 23400

caaattacca caactcaccc aatatgaaat agataattgg gatagcctga taactactga 23460

gaaaattgaa tttgtaattt taacactctt aaaacagaaa cattaaactt aatattttat 23520

aaatattaga taaggtaatt atacccttcc ttaacaaata aaaacgacaa attattttgc 23580

agctaaagag atgtatgtac tgtgaaaaat atcttcagaa aaatagaact ttgtttgaag 23640

aataaggatt taaaaaatgt ttttaactct caagaagcaa atatctgggc ccagatggtt 23700

tcactgaaga attctaccaa atgtttaatg aagaattacc accaactcta catagcatct 23760

ttgagaaaac tgaagagaag ggaacatctc ccagttcatt ttatgaagtg ggtgttactc 23820

tgatactaga actgtataag gacagctact cttgacacac tgcctatggg tagctctgct 23880

ctgcaggaac agtcagaaaa aaaaaaaaaa gaagcactgg acaagggcag tataaaaaaa 23940

gaaaactggg ccaggtgcag tggctcacac ctgtaatctc agcactttgg gaggctgacg 24000

ctggtggatc acctgaggtc aggagtttga gactagcctg gccaacatgg taaaaccctg 24060

tctctactaa aatacaaaaa ttagccaggc agggtggtgg ggaaaataaa aaggaaaaaa 24120

aaacaaaaat aaactgcaga ccaatatcct tcatgagtat agacacaaaa ctccttaaac 24180

tccttaacaa aatattagca agtagaagca atatataaaa ataattatac accatgatca 24240

agtgggactt attccagaaa cgcaagtctg gttcaacatt tgaaaacaag gtaacccact 24300

atatgaacgt actaaagagg aaaactacat aatcacatca atcaatgcag aaaaaagcat 24360

ttgccaaaat ccaatatcca ttcatgatac tctaataaga aaaataagaa taaaggggaa 24420

attccttgac ttgataaagc ttacaaaaga ctacaaaagc ttacagctaa cctatactta 24480

atggtgaaaa actaaatgct ttcccctacg atcaggaaca aagcaaggat gttcactctc 24540

attgctctta tttaacatag ccctgaagtt ctaacttgtg caaaacgata agaaagggaa 24600

atgaaagacc tgcagattgg caaagaagaa ataaaactgt tcctgtttgc agatgacatg 24660

attgtctcat agaaaatgta aagcaactag gggtaggggg gcagtggaga cacgctggtc 24720

aaaggatacc aaatttcagt taggaggagt aagttcaaga tacctattgc acaacatggt 24780

aactatactt aatatattgt attcttgaaa atactaaaag agtgggtgtt aagcgttctc 24840

accacaaaaa tgataactat gtgaagtaat gcatacgtta attagcacaa cgtatattac 24900

tccaaaacat catgttgtac atgataaata cacacaattt tatctgtcag tttaaaaaca 24960

catgattttg gccaggcaca gtggctcata cctgtaatcc cagcatttta ggaggctgag 25020

gcgagcagaa aacttgaggt cgggagtttg agaccagaat ggtcaacata gtgaaatccc 25080

gtctccacta ataatacaaa aattagcagg atgtggtggc gtgcacctgt agacccagct 25140

acttgggagg ctgaggcacg agaattgctt gaacaaggga ggcagaggtt gcagtgagct 25200

gggtgccact gcattccagc ctggtgacag agtgagactc catctcaaaa aaaataaaat 25260

aaagcatgac ttttcttaaa tgcaaagcag ccaagcgcag tggctcatgc ctgtaatccc 25320

accactttgg gaggccgagg caggcagatc acaaggtcag gagtttgaga ccagcctgac 25380

caacatggtg aaaccccatc tctactaaaa aatatataaa ttagccaggc atgtgtagtc 25440

tcagctactc aggaggctga ggcaggagaa tcacttgaac ccggaggcag aggttgcagt 25500

gttgagccac cgcactccag cctgggtgag agaacgagac tccgtctcaa aaaaaaaaag 25560

caaaataacc taattttaaa aacactaaaa ctactaagtg aattcagtaa gtctttagga 25620

ttcaggatat atgatgaaca tacaaaaatc aattgagctg gacaaaggag gattgtttta 25680

ggtcagtagt ttgaggctgt aatgcacaat gattgtgcct gtgaatagct gctgtgctcc 25740

agcctgagca gcataatgag accacatctc tatttaaaaa aaaaaaaatt gtatctctat 25800

gtactagcaa taagcacatg ggtactaaaa ttaaaaacat aataaatact gtttttaatt 25860

gcctgaaaaa aatgaaatac ttacatataa atctaacaaa atgtgcagga cttgtgtgct 25920

gaaaactaca aaacgctgat aaaagaaatc aaagaagact taaatagcgt gaaatatacc 25980

atgcttatag gttggaaaac ttaatatagt aaagatgcca attttatcca aattattaca 26040

caggataaca ttattactac caaaatccca gaaaaatttt acatagatat agacaagatc 26100

atacaaaaat gtatacggaa atatgcaaag gaactagagt agctaaaaca aatttgaaaa 26160

agaaaaataa agtgggaaga atcagtctat ccagtttcaa gacttacata gctacagtaa 26220

tcaagactgt gatattgaca gagggacagc tatagatcaa tgcaaccaaa tagagaacta 26280

agaaagaagc acacacaaat atgcccaaat gatttctgac aaaggtgtta aaacacttca 26340

acgggggaag atatgtctct cattaaaggg tgtagagtca ttgcacatct ataggcaaaa 26400

agatgaacct gaacctcaca ccctacagaa aaattaactc aaaatgactc aaggactaaa 26460

cataagatat acatctataa aacatttaga aaaaggccac gcacggtggc tcacgctcgt 26520

aatcccagca ctttgggagg ccaaggcagg tggatcacct aaggtcagga gtttgagacc 26580

agccggatca acatggagaa gccccatctc tactaaaaat acaaaattag ctggacgtgg 26640

tggcacatgc ctgtaatccc agctacttgg gaggctgagg catgagaatc gcttgaaccc 26700

ggggggcaga ggttgcggtg agccaagatc acaccattgc actccagcct gggcaacaag 26760

agcaaaactc caactcaaaa aaaaaaaaaa aaaggaaaaa tagaaaatct ttgggatgta 26820

aggcgaggta aagaattctt acacttgatg ccaaactaag atctataagg ccagtcgtgg 26880

tggctcatgc ctgtaattcc agcactttgg tcaactagat gaaaggtata tgggaattca 26940

ctgtattatt ctttcaactt ttctgtaggt ttgacatttt tttagtaaaa aattggggga 27000

aagacctgac gcagtggctc acacctgtaa tcccagcact ttgggaggcc ggggcaggtg 27060

gatcacacgg tcaggagttc gagaccagcc tggccaacat ggtgaaaccc cgtctctacc 27120

aaaaatataa aaaattagcc gggtgtcatg gtgcatgcct gtaatcccag ctactgagga 27180

ggctgaggca ggagaatcac ttgaacctgg gaggtggaag ttgcagtgag ccgagattgt 27240

gccactgcac tccagccttg ggtgacagag cgagactccg tctcaaaaga aaaaaaaaaa 27300

aaagaatatc aaacgcttac tttagaaact atttaaagga gccagaattt aattgtatta 27360

gtatttagag caatttttat gctccatggc attgttaaat agagcaacca gctaacaatt 27420

agtggagttc aacagctgtt aaatttgcta actgtttagg aagagagccc tatcaatatc 27480

actgtcattt gaggctgaca ataagcacac ccaaagctgt acctccttga ggagcaacat 27540

aaggggttta accctgttag ggtgttaatg gtttggatat ggtttgtttg gccccaccga 27600

gtctcatgtt gaaatttgtt ccccagtact ggaggtgggg ccttattgga aggtgtctga 27660

gtcatggggg tggcatatcc ctcctgaatg gtttggtgcc attcttgcag gaatgagtga 27720

gttcttactc ttagttccca caacaactgg ttattaaaaa cagcctggca ctttccccca 27780

tctctcgctt cctctctcac catgtgatct cactggttcc ccttcccttt atgcaatgag 27840

tggaagcagc ctgaagccct cgccagaagc agatagtgat gccatgcttc ttgtacagcc 27900

tacaaaacca tgagcccaat aaaccttttt tctttataaa ttatccagcc tcaggtattc 27960

ctttatagca agacaaatga accaagacag ggggaaatca acttcattaa aataatctat 28020

gcagtcacta aacaaataag aacaagaggc tccagaagtg ggaagccaat acccagagtt 28080

cctacaatac agtatctgaa aagtccagtt tccaaccaaa aaatatatat atacaggccg 28140

gacatggtag cttatgtctg taatcccagc actttgggat gctgaggcgg gcagatcacc 28200

ctaggtcagg agttcgagac cagcctggcc aatatggcaa aaccccgtct ctactaaaaa 28260

tacaaaaatt agccaggcat ggtggtggat gcctgtaatc ccagctactc gggaggctga 28320

ggcagggaat cacttgaacc caggaggcag aggttgcagt gagccgagat cacgccactg 28380

aactccagcc tgggcaacaa agtgagactc cacctcaaaa aaaaaaaaaa tatacatata 28440

tatatgtgtg tgtgtgtgtg tgcgcgcgtg tgtgtatata cacatacaca tatatacata 28500

tatacagaca cacatatata tatgaagcat gaaaagaaac aaggaagtat gaaccatact 28560

ttctgtggtt atgataggat ggggtatcac gggggaagta gacaagggaa actgcaagtg 28620

agagcaaaca gttatcagat ttaacagaaa aagactttgg agtaaccatt ataaatatgt 28680

ccacagaatt aaagaaaagc gtgattaaaa aaggaaagga aagtatcata acaatattac 28740

tccaaataga gaatatcaat aaaggcatag aaattataaa atataataca atggaaattc 28800

cggagttgaa aggtagaata actaaaattt aaaattcact agagaaggtt caacactata 28860

tttgaactgg cagaagaaaa atttagtgag acaaatatac ttcaatagac attattcaaa 28920

tgaaaaataa aaagaaaaaa gaatgaagaa aaataaacag aatctcagca aaatgtggca 28980

caccattaat cacattaaca tatgcatact gagagtaccg gaagcagatg agaaagagga 29040

agaaaaaata ttcaaatgat ggccagtaac ttcctagatt tttgttttaa agcaataacc 29100

tatacaatca agaaactcaa tgaattccaa gtaggataaa tacaaaaaga accacaaaca 29160

gatacaccat ggtaaaaatg ctgtaagtca aaaacagaga aaatattgaa agcagctaga 29220

ggaaaactta taagagaacc tcacttacaa aagaacatca cttataaaag aaccacaata 29280

atagaaacag ttgacctctc atcagaaaca atgaatgata acatatttga agtgctcaaa 29340

gaaaaaaaat aaagattcct atatacgaca aagctgtctt tcaaaaatat acatccaaaa 29400

ggattgaaac cagggtcttg aagagttatt tgtacatcca tgttcatagc agcattattc 29460

acaatagcca aaaggtagaa gcaacccaag ggtccatcga caaataaata aaatgtggta 29520

tatgtataca caatggaatt tattcagtat taaaaaggaa tgaaattctg acacatgcta 29580

caacatggct aaaccttgag aacactatgc taagtgaaat aagccagcca caaaaggaca 29640

aataccatat tacttcactt gtatgaaata cctagggtag tcaaattcag agatagaaag 29700

taaaacagtg gttgccaagg gctgagggag ggagtaacgt ggagttattg ttgaatgggt 29760

acagaatttc agttttgcaa gataaaaaga gttctggaga cagatggtgg tgagggtggt 29820

acaacaatac aaatatactt tatactactg aacagtatac ttaaaaatga ttaacatggt 29880

gaaaccccgt ctctactaaa aatacaaaaa aattagctgg gtgtggtggc gggcacctgt 29940

aatcccagct acttgggagg ctgaggcagc agaattgctt gaaaccagaa ggcggaggtt 30000

gcagtgagct gagattgcgc caccgcactc tagcctgggc aataagagca aaactccgtc 30060

tcaaaaaata aaaaataaaa aaaatttaaa aatgattaag caggaggcca ggcacggtgg 30120

ctcacaccta taatgccagc actttgggag gccgaggcag gcgatcactt gagaccagga 30180

gtttgagacc agcctggcca acatggcaaa accctgtctc tgctaaaaat acaaaaatta 30240

gccaggcatg gtggcatata cttataatcc cagctactgg tgagactgag acacgagaat 30300

tgcttgaacc caggaggcag agattgcagt gagtcgagat cgcgccactg aattccagcc 30360

tgggcgacag agcaagattc tgtctcgaaa aaacaaaaac aaaaacaaaa agcaaaacca 30420

aaaaataatt aagcaggaaa cgagattgct gctgaggagg agaaagatgt gcaggaccaa 30480

ggctcatgag agcacaaaac ttttcaaaaa atgtttaatg attaaaatgg taaattttat 30540

atgtatctta ccacaaaaaa aagggctggg gggcaggaaa tgaaggtgaa ataaagacat 30600

cccagagaaa caaaagtaga gaatttgttg ccttagaaga aacaccacag gaagttcttc 30660

aggctgaaaa caagtgaccc cagagggtaa tctgaattct cacagaaaat tgaagcatag 30720

cagtaaaggt tattctgtaa ctatgacact aacaatgcat attttttcct ttcttctctg 30780

aaatgattta aaaagcaatt gcataaaata ttatatataa agcctattgt tgaacctata 30840

acatatatag aaatatactt gtaatatatt tgcaaataac tgcacaaaag agagttggaa 30900

caaagctgtt actaggctaa agaaattact acagatagta aagtaatata acagggaact 30960

taaaaataaa attttaaaaa atttaaaaat aataattaca acaataatat ggttgggttt 31020

gtaatattaa tagacataat acaaaaatac cacaaaaagg gaagaagaca atagaactac 31080

ataggaataa cattttggta tctaactaga attaaattat aaatatgaag tatattctgg 31140

taagttaaga cacacatgtt aaaccctaga tactaaaaag taactcacat aaatacagta 31200

aaaaaataaa taaaataatt aaaatgtttg tattagtttc ctcagggtac agtaacaaac 31260

taccacaaat tgagtggctt aacacaactt aaatgtattt tctcccagtt ctggaggcta 31320

aacacctgca atcaaggtga gtacagggcc atgctccctg tgaaggctct aggaaagaat 31380

cctcccttgt ctcttccagc ttccagtggt tctcagtaac cctaagtgct ccttggcttg 31440

tagctatatc attcctagca accagaaaga agaaaataat aaagattatg gcaaaaaata 31500

atgaaatcaa aaggagaaaa atggaaaaaa ataaataaaa ccaaaagcta gttctttgaa 31560

aagatcaacc aagttaacaa accttttaac tagactgaca aaaaggaggt aagactcaaa 31620

ttactagaat cagaaataaa agaggggaca ttactaatga gggattagaa aagaatacta 31680

cgaacaaatg tgtgccaaca aattagaaaa cttagatgaa atggacaggt tcctaggaca 31740

acatcaacta ccaaaattta ctcaagaaga aagagacaat ttgaatgagc tataacaagg 31800

gaagagactg aattgacaac caagaaacta tccacaaaga aaatcccagg cccagaagat 31860

ttcactgtga aattctttca aacttataaa tataaattaa catcagttct tcacaaactc 31920

ctccaaaaaa aagaacagat ctctatttac aggcgatacg atctttagaa aatcctaagg 31980

gaactactaa gacactatga taactgataa acaagttcag caaggctgca ggatagaaaa 32040

ccaatataca aaaatctatt atatttctat acacttgcag tgaacaaccc aaaaatgaga 32100

ttaagaaaat aattcaattt acaataacat caaaaagaat aaaaacactc aaaaataaat 32160

ttattcaagt aagtgcaaaa cttatactct agaagctaca aaacactgtt aaaagaaatt 32220

aaaggtttac ataaatgaaa aactatccca tgttcatgga tcaaaagact tattactggc 32280

aatgctctcc aaattgatct ataaattcaa caaaatcctt atcaaaatcc cagatgaggc 32340

tgggggtggc ggttcatgcc tgtaatccca gcactttggg aggctgaggc acgcagatta 32400

cctgaggtcg ggagctcgag atcagcctga ccaacatgga gaaaccctat ctcttctaaa 32460

aatacaaaat tagtcaggcg tggtggcaca tgcctataat cccagctact cgggaagctg 32520

aggcaggaga atcgcttgaa cccaggaggc agaggttgca gtgagccaag atcgtgccat 32580

tgcactccag cctgggcaac aagagcaaaa ttccatctca aaaaaaaaaa aaaaaaaatc 32640

ccagatgact tcactgttga aattgaaaag attattctaa aattcacatg gaattgcaag 32700

accttgagaa tagccaaaac aaacttgaaa aacacgaaca aaatatagga tgactcactt 32760

gccaattgca aatgttacga cacagcaaca gtaatcaaga ctgtgtggta ctggcaaaag 32820

acacatacat acatacatat caatggaata taattgagag tacagaaaca agcctaaaca 32880

tctatggtaa gtgcttttct atttttttct tttttttttt cttttttgta gagatagaat 32940

ctcaccatgt tgcccaggct ggtcttcaac ttctgggctc aagcaatcct cccactgtgg 33000

cctcccaaag tgctgggata actggcatga gccaccacat ccagcccaga tgattttcaa 33060

aaaagtcaac aagaccattc ttttcaacaa ataggtctgg gatgatcaga tagtcacatg 33120

aaaaaaaaaa tgaagttgga ccctccatca cactaaagtg ctgcgattat aggcatcagc 33180

caccacatcc agcccaaatg attttcaaaa aggtcaacaa gaccattctt ttcaacaaat 33240

aggtctggga taatcagata gtcacatgaa aaaaaaaatg aagttggacc ctccatcaca 33300

ccatatgcaa aaattaattc aaaaatgaat tgatgactta aacgtaagag ttacgactgt 33360

aaaactctta gaaggaaaca tacgggtaaa tcttaaagac gttaggtttg acaaagaatt 33420

cttagacatg acaccaaaag catgaccaac taaggtaaaa tagggtaaat tgtacctacc 33480

aaaatgaaaa acctttgtgc tggaaaggac accatcaaga aatggaaagc caaaatagcc 33540

aaggcaatat taagcaaaaa gaacaaagct ggaggcatca tactacctga cttcaaagca 33600

acagtaacca aaacagcatg gtactagtag aaaaacagac acatagacca atggaacaga 33660

ataaagaacc caaaaataaa tccacatatt tatagtcaac tgatttttga caatgacacc 33720

ccttcaataa atgatactag gaaaactgga tatcgatatg cagaagaata aaactagacc 33780

cctatctctc accatataga aaaatcaact cagactgaat taaagacttg aatgtaagac 33840

ccaaaactat aaaactactg gtagaaaaca taaggaaaaa cgcttcagga cattggtcca 33900

ggcaaagatc ttatggctaa aacctcaaaa acacaggcaa caaaaacaaa aatggaaaaa 33960

tagcacttta ttaaactaaa aagctcctgc acagcaaagg aaacaacaga atgaaaagac 34020

aacctgtaga atgggagaaa atatttgcaa actatccatc catcaaggga ctagtatcca 34080

gaacacacaa gtgactaaaa caactcaaca gcaaaaaagc aaataatctg gtttttatat 34140

gggcaaaaga tctgaataaa cattctcaaa ggaagacata caaatgtcac tatcattctg 34200

ccagtaccac actgtcttga ttacttgtta gtgtataaat ttttaaattg ggaagtgtga 34260

gtcatcctac actttgttct tgtttttcaa gtttgttttg gctattctgg gagccttgca 34320

agtataaaat agccaacaag tatgaaaaaa tgctcaccat cactaatcat cagagaaata 34380

aaaatcaaga ccactatgag atatcctctc actccagtta gaatggctac tatcaaaaag 34440

acaaaatata atggatgctg gcaaagattt ggagaaaggg gaactcctat acactgtggg 34500

tagggatgca aattggtaat ggccattatg gaaaataata ctgaggtttt tcaaaaaact 34560

gaaaatagaa ctaccatatg atccagcaac cctactactg ggtatttatc caaaggaaag 34620

aagtcagtat actgaagaaa tatatgcact ctcatgttaa ttgcaacact gttcacaaca 34680

gccaagacag ggaataaatc taaatgtgca tcaacagatg aatggataaa gaaaatgtgg 34740

catatacact caatagaata ctattcagcc attaaagaag aatgaaatcc tgtcatccca 34800

gcaacatgga tgaacctgga ggacattata tttaatgaaa taagtaaagc acaaaaagat 34860

aaacagtaca tgttctcact cagacatggg tgctaaaaag aaaatggggt cacagaatta 34920

gaaggggagg cttgggaaaa gttaatggat aaaaatttac agctatgtaa gaagaataag 34980

ttttagtgtt ctatagaact gtagggcgag tatagttacc aataacttat tgtacatgtt 35040

caaaaagcta gaagagattt tggatgttcc cagcacaaag gaatgataaa tgtttgtgat 35100

gatggatatc ctaattaccc tgattcaatc attacacatt gcatacatgt atcaaattat 35160

cactctgtac ctcataaata tgtataatta ttacgtcaac aaaaaaagga aaaaaaagaa 35220

aattaagaca acccacataa tggaagaaat aaaatatctg caaattatat atatctgata 35280

aatatttaat atttataata tataaagaac tcctacaact caagaacaac aacaaaacaa 35340

cccaattcaa aaatgggtaa aagccttgaa tatacactta tctaaagact atatacaatt 35400

ggccaataaa gacacgaaaa gatgctcaac atcactagtc atcagggaaa tataaatcaa 35460

aaccacaatg tagaatgtag acaccacttc atatgcacta ggatggctag aataaaaagg 35520

taataacaaa tgttggtaag gatgtgaaaa aatcagaaac ctcattcgct gctgttggga 35580

atgtaaagtg atgcagccac tttggaaaac agtctggcag ctcctcaaat tattaaatac 35640

agagttaccg tatgacccag gaatattcct cctgggtcta taaccaaaaa aatgaaaaca 35700

tatatccaca taaaaacttg tacatgggca tttatagcaa cattattcat aacagcaaag 35760

gtggtaagaa cccatatgcc catcatctga tgaacaggta aataacatgc ggtattatcc 35820

atacactaga atattatctg cccatacaag gagtgacatc cagctacatg ctacaaggat 35880

gaatctcgga aaccttatgc taagtgaaag aagccagtca caaatgacca cagattatga 35940

ttccatgcat cggaaatgac cagaataggg aaatctatag agacagaaag tagattagtg 36000

gttgggtggg gctgggagga caggtagtac actactttcc cagaactact ggaacaaagt 36060

accacaaact ggggagctta aacatagaaa ttgatttcct cacagttctg gagactagga 36120

ctctgagatc aaggtgtcag cagagctggt tctttctgag ggccctgagg caaggctctg 36180

tcccaggcct ctctccttgg ctggcaggtg gccatcttct ccctgcgtct tcacatcatc 36240

ttttctctgt gtgtgcccat gtccaaattt tgattggctc attctgggtc atggccaatt 36300

gctatgcaca aagtgaagtc tacttccaaa agaagggaag agggaacact gactaggcta 36360

aacttatagt cattttaatg tccgcttttc ctatgagatt gtgaacacac agaagtaggg 36420

tttttatcta cattgtgcaa agtttaataa gaaaaataga attcaagaga agcagttcaa 36480

tagcaggaat ttaatatggg aactaattac aaggtttagg gcaggactaa aaagccagtt 36540

gggatggtga gccaacccag agattagcaa cagtgggacc ccatctacct accacccatg 36600

aagctggaag gataaaggag gggctattat cagagtccac aagccagtgt cagagtcctt 36660

ggctggagct gggaccaccc tagagacact gtgcaaagca gaaaacaagg gggaaaaacc 36720

ctgacttctc ccttcctccc acctttcaat ctcccactag tgcttcctac tagccatact 36780

tggccagaga cagtgacaag gaacactgca aaatgaagtt tgtaggaatc atctccctct 36840

gagacagaga aatatggaag ggtagaaaat gaatcagagg ataaagagaa aaaaccctga 36900

gtactatctt atttatcttt gtatctccag tgcctaatct gtctctcaaa aaaggaaagc 36960

aattgagaga aactgaaaac tccaattgaa atgaaagaat ggagaattac tggactagaa 37020

gagaagagaa aaatttattc cgcatagagt aaacaagaat ggattcacaa aggacgtgat 37080

gaatgaaaag ctataatcag caaagatttg ccagagaaat taaaaagtgg taaactcagc 37140

cacgctgtac aacctgaagg cacaatgcat gaaaacgttt caagaaatga caagatttga 37200

agtcaaattc taagtgcttt tccagaatct ctcaagacga ttatatagct accccatttt 37260

attaaataaa atggaaactt actaaacttt ccccttgtat taaactaaca tatgtcctaa 37320

tagcaaacga ttctggaatt cctagagtaa aatatatttc gtcaaagtgt attgctcttt 37380

taatattctg ctgacctcct tttgctattt aggatatttg tatacacatc acacgtaaat 37440

ttggtctata gtttacatct acgggcttat actgttcttt ttttcatttt tttaaaattt 37500

ccaaccccca gtatccatat actgctctct atcagggtta ttttaacttt gtaaaatcag 37560

ctgagatgct ttccatgttt ttttttttta ttttctgcca catttgaata gcataggagt 37620

taccaccatc aaccttggat tatttaagca ttcacgattc cacgtgtgga ttttttattc 37680

agagtctttc ttgtcattcc tgctatcagc acagaaccca atctcagctt tccagctata 37740

ctctcacccc atggaatttg cagatgaagt tcaaaaggac ctttgcatta tcctgcctcg 37800

ccctcttccc ccttcattta gacatcacct tcttctagaa cgtcttacct gacatgccct 37860

gctcccaacc cctgctgccc aattgtgtgc tctcccgtgt cctggcctgc catcctcttt 37920

agtaattgcc tgctccctca tctgtctccc cacccagaca ttaagctgaa tagactggat 37980

ttgtgtcttg tccatcacta taatctcagc acctagtacc tagtaggtac ttaccatgta 38040

ttcattagca aaatgttatg tataaccttg caccttaaaa acaagagaag gaagacaaaa 38100

ttaagtctta agactatggt ttagaacatg gatcagaaac tacagtctgc agcccaaatc 38160

cagaccaaat gaagagacca tgttcattta catacaacct atagcagctt tcacactaca 38220

ggagcagagc taagtagttc caagggaaca cacggccctg caaagcctaa aatatttact 38280

ctatagctct tcacagaaaa agttttcaga tccctcgttt agaactcttg ttcatatgca 38340

atttcactaa accatagttt tttgggtttg tttggttttt tttggcaaaa aggaatgagc 38400

cgatccagaa aaggttgaaa agaatgaatc attactgctg aaagaatgtg cacacagtcc 38460

gtcagtattc tgctgccatg ctgacaccca tccaatagtg tcatgagatg cagcagctac 38520

tactgtgttc tcaatgccga gtccacccac tccataacca tgtccaagca atcttgggaa 38580

catcatcacc atgcttgttt atccttaagg tattgcctca catacagcag tggctggtca 38640

taaagtcaaa tgacactagt ggccaggagg tcaagagaat gagtgaggac aggtgggtag 38700

gcagcccagg ccctagcaac agcaggagct cacccctcag tcactctagc caggactgaa 38760

atacttttca ccctttcaag agagactagg aatctggatt tttatgtgaa atatcttgat 38820

tactaaatgt tgtcaacaga catgtcaaaa ggtaaaacta agtaagttca tggggcagat 38880

tgactattca ggttatagaa ttaaggattc ttatccaaca cagataccaa ccaaaaagct 38940

gacgtataac atattaggag aaactatgtg cactgtcgaa acatcaacaa ggggctaatg 39000

tctaaaatag tctatattgg attccagttg aaacatgggg aaaggacatg aacaggcaac 39060

ttatgtcaat ggaaactcaa aaagataaca agcatatata aaagcattct caaattcagt 39120

agtaaacaga cagatgcaaa taaaaagagg gaaactgctg ccgggcacag tggctcacac 39180

ctgtaatccc agcactttgg gaggccgagg cgggcggatc atgaagtcag gagatcgaga 39240

ccatcctggc taacatggtg aaaccccgtc tctactgaaa acacaaaaaa ttagccaggc 39300

gtagtggtgg gcaccagtag tcccagctac tcaggaggtt gaggcaggag aatggcatga 39360

acccaggagg cggagattgc agtgagccga gaccatgcca ctgcactcca gcctgggcga 39420

ctgagtgaaa ctccatctca aaaaatataa taataattat aattataata ataataaata 39480

gtaaataaat aaaaagagag agactgctaa agtctagaaa gttgaatgat gccaagcgca 39540

tgcaaagatc agggccttgg gatggccggg tgcagtggct cacgcctgta atcccaccac 39600

tttgggaggc caaggcgggc ggatcatgag gtcaagagat caagaccatc ctggccgaca 39660

cagtgaaacc cggtctctac taaaagtaca aaaaaatata tatatatata tatattatta 39720

tattatatat atatatatca gagccttggg aatccttgtg tgctgctggg gaaggtagtg 39780

gtgcagccac ccttgacagc aatctggcag tacttggtta tattaagtat aggcacacac 39840

cacgaccagg cagtcctact cctgggtcta aatcccaaag aattctcaca caagtccata 39900

aggagacatg tacgaggctc attcagcatt actgggagtg ggaatcaacc tgggtgtcca 39960

tctacaggag acgagatgga caaaatgtgg tggatattaa gaccagaatc accaagtaac 40020

agagatgggt ggtgagtgac aatcctaaga tacagaataa aggctagaac atgatgccat 40080

tcatgtaaat taaaaataga tgcacacaaa gcagtatacg cgtgaccctt gaatagcaca 40140

ggtttgaact gcctgtgtcc acttacatgt ggattttctt ccacttctgc tacccccaag 40200

acagcaagac caacccctct tcttcctcct ccccctcagc ctactcaaca tgaagatgac 40260

aaggatgaag acttttatga taatccaatt ccaaggaact aatgaaaagt atattttctc 40320

ttccttatga ttttctttat ctctagctta cattattcta agaatatggt acataataca 40380

catcacacgc aaaataaatg ttaattgact gtttatatta tgggtaaggc ttccactcaa 40440

cagtaggctg tcagtagtta agttttggga gtcaaaagtt atacacagat tttcaactgt 40500

gcaggcaatc agttcccctg accccctcat tgttcacggg tcaactgtat atacacaaaa 40560

gtattatatg aacctcatta gaatagctgt ctatagggag aagagaatga gagtgggata 40620

aaacggaatg aacaaataaa ccaacaaatg cattaacaag caaaacaaca gaggggcttg 40680

catgggccag tgatgataaa gggctaagaa tgagaatata attaattcaa ttcctcacac 40740

ctgaggtcta aaaccaagga aagggagggc caggcgtgga ggctcacgcc tgtaatccca 40800

gcactttggg aggctgaggc gggcggatca caagattagg agtttgagat cagcctggcc 40860

aacacagtga aagcccatct ctacaaaaaa tacaagaatt acccaggtgt ggtggcacat 40920

gcctgtagtt agctactctg gaggctgagg caggagaatc acttgaaccc aggaggcgga 40980

ggttgcaggg agccgagatc acaccattgc actccagcct gggtgacaga gtaagactct 41040

gtctcaaaaa aataaaaaaa ataaaaaaac agagaaaggg aggaaactag atccaggctg 41100

actagataca gcctttagag ttagaaaaga tgatttgaca atctaagccc acactcagat 41160

tgaatgaaat tgaaaagcct ttcaaactaa aacatttaat tacaccatct gctgcagaca 41220

gaactcagac aactcaaaca ggtaatgtca gcgtggtgtt ttatatcacc accctcaaca 41280

cagaataaaa atcagctgca tgtgaagcag tgactagaat gaagaaaagg ctgcttctta 41340

cttccttcta gtggttcttt ccgaaaacat taataggcac cagctctatg catgtcaccc 41400

tgcagggaga catggggtat ataactatga cttactgttc attcctcaag gaattcccaa 41460

tcttgtggaa gattatacac aatgaggcaa caaaaactat ccaataaaac cacggaaaag 41520

aagccagtga caaagaagcc agtgatgaaa ggccctgtga gcagagctga tggccatttg 41580

gggaagaaag accaacatgg atgggggtga tcagggtggc tccgtgggaa agctggaaga 41640

gaagtggcag atctctgagc tggatgatgg gccactacca tctgtatatg gctaattaaa 41700

gaccatgtgt ggatttttta ttcagctctt tcgtgtcatt cctgctatca gcacagaacc 41760

caatctcaac tttccagcta tattgagcta aacttctcac ctcatggaat ttgcagataa 41820

agttcaaaag gatccttgcc ttttcaaaat aattttgaat ggttgagtag tccctctgtg 41880

ctctctcact gacaccctct caaggctgct gagcacgtgc catgctatgg ctttctccaa 41940

catcaggaaa tgttctccac tcagtttcac cttaatacaa atgtgttctc tcttcagaga 42000

aggcaaaaaa attcatgacc atctgactgg gagaagtcat ttctaggtaa agtgtccatc 42060

tttttctgag gaacacagga ggaaaatctt acagaaaaga gttaacacag caggcctaag 42120

actgcttttt aaaataaata aataaataaa taaataaata aataaataaa taaataaata 42180

aataaatgaa tgatagggtc ttctgtattg gccaggctag tctcaaattc ctggcttcaa 42240

gagatcctcc caccttggtc tcccacagtg ttgggattat agacatgagc cattgtgctt 42300

ggcccaagac tgttattctt aaaaagtctc ataaaaagca tggttaatcc ttggctggca 42360

cctgggaact tagatttcag aagggttccc accatccaac ctggaaagag ggactcactg 42420

tgcctaaatt attgtgtggt ttatgctgaa ctcctgcttt tcttcaggta gcgtggaatg 42480

tggtatgtgc tgggcaaagg gggcctgcat gaccagcccc caataaaaac cctgggtgtt 42540

gggtctctag tgagtttccc tggtagacag catttcacat gcgttgtcac agctccttcc 42600

tcggggagtt aagcacatac atcctgtgtg actgcactgg gagaggatgc ttggaagctt 42660

gtgcctggct tcctttggac ttggccccat gcacctttcc ctttgctgat tgtgctttgt 42720

atcctttcac tgtaataaat tacagccgtg agtacaccac atgctgagtc ttccaagtga 42780

accaccagat ctgagcatgg tcctgggggc ccccaacaca gaaataaatt ataaaagacc 42840

aaggactggg catggtggcc catgccggta atctcagcgc tttgggaggc cgaggcagga 42900

ggaccagtta agcccaaaag ttcaaagtta cagtgaccta tgactgcgcc aatgcactct 42960

aacctgggag acagagcaag accctgtccc caaaacaata aactaaacac atacttctgc 43020

cttccaagtg tcttaaaatt caatggaatg gtagaaacat ttttaaaaca ctaaatcaaa 43080

agaaacctgg aaaacaagag tgccgatggc caactaaaat gtctaggaaa tttctgaaaa 43140

gtaaaaagta ctcagaacca gattacctga gcaaaccata gcccaataca agcttgggag 43200

gaggctgtta tgcagaagga aatggtaaca ggtttccagg aacagacttg taacagcaga 43260

tagaacagca gaggtagaac ctgacaaggt gattacctgg ggaactgcag tctgaatgac 43320

caggactgtt ggacccttcc cctcacatgg aatacacacg ccactcagca gcacaccaca 43380

gctcttcaac aatcacagga ggcacgctac gcctagtaag acaggaaaaa aggaattctc 43440

aaacttcgaa gatgaacaca taaagaatca ccaagttttt attcagtatg atgaaacagg 43500

gacactgaat caacagaaca caaacccaag caaagataat tactagagca catagaagaa 43560

attattagat attcttggga agacctaagg ggacattata aagagcaagc agttggtatg 43620

tgacgatctt tgtgatatac caagaaataa aaacacagga tgaagaccag atagagaata 43680

atgctactat ttgtgcaaaa aaggagaaat ggagaatctg attcatattt gcttgtattt 43740

gcatgaagaa actttggaag gtacataagt aactaacaac aatggttacc tacttgtaag 43800

gcgagagaag taagaggaca ggaatggtgg gaacaccttt tgtgtccgga attggtgggt 43860

tcttggtctg acttggagaa tgaagccgtg gaccctcgcg gtgagcgtaa cagttcttaa 43920

aggcggtgtg tctggagttt gttccttctg atgtttggat gtgttcggag tttcttcctt 43980

ctggtgggtt cgtagtctcg ctgactcagg agtgaagctg cagaccttcg cggcgagtgt 44040

tacagctctt aagggggcgc atctagagtt gttcgttcct cctggtgagt tcgtggtctc 44100

gctagcttca ggagtgaagc tgcagacctt cgaggtgtgt gttgcagctc atatagacag 44160

tgcagaccca aagagtgagc agtaataaga acgcattcca aacatcaaaa ggacaaacct 44220

tcagcagcgc ggaatgcgac cgcagcacgt taccactctt ggctcgggca gcctgctttt 44280

attctcttat ctggccacac ccatatcctg ctgattggtc cattttacag agagccgact 44340

gctccatttt acagagaacc gattggtcca tttttcagag agctgattgg tccattttga 44400

cagagtgctg attggtgcgt ttacaatccc tgagctagac acagggtgct gactggtgta 44460

tttacaatcc cttagctaga cataaaggtt ctcaagtccc caccagactc aggagcccag 44520

ctggcttcac ccagtggatc cggcatcagt gccacaggtg gagctgcctg ccagtcccgc 44580

gccctgcgcc cgcactcctc agccctctgg tggtcgatgg gactgggcgc cgtggagcag 44640

ggggtggtgc tgtcagggag gctcgggccg cacaggagcc caggaggtgg gggtggctca 44700

ggcatggcgg gccgcaggtc atgagcgctg ccccgcaggg aggcagctaa ggcccagcga 44760

gaaatcgggc acagcagctg ctggcccagg tgctaagccc ctcactgcct ggggccgttg 44820

gggccggctg gccggccgct cccagtgcgg ggcccgccaa gcccacgccc accgggaact 44880

cacgctggcc cgcaagcacc gcgtacagcc ccggttcccg cccgcgcctc tccctccaca 44940

cctccctgca aagctgaggg agctggctcc agccttggcc agcccagaaa ggggctccca 45000

cagtgcagcg gtgggctgaa gggctcctca agcgcggcca gagtgggcac taaggctgag 45060

gaggcaccga gagcgagcga ggactgccag cacgctgtca cctctcactt tcatttatgc 45120

ctttttaata cagtctggtt ttgaacactg attatcttac ctattttttt tttttttttt 45180

tgagatggag tcgctctctg tcgcccagac tggagtgcag tggtgccatc ctggctcact 45240

gcaagctccg cctcccgggt tcacaccatt ctcctgcctc aacctcctga gtagctggga 45300

ctacaggcaa tcgccaccac gcccagctaa ttttttattt tatttttttt ttagtagaag 45360

cggagtttca ccatgttagc cagatggtct caatctcctg acctcgtgat ccatccgcct 45420

cggcctccca aagtgctggg attacagacg tgagccactg cgccctgcct atcttaccta 45480

tttcaaaagt taaactttaa gaagtagaaa cccgtggcca ggcgtggtgg ctcacgcctg 45540

taaccccagc actttgggag gccgaggcgg gcggatcacg aggtcaggag atcgagatca 45600

tcctggttaa cacagtgaaa ccccgtcgct actaaaaata caaaaaatta gccgggcgtg 45660

gtggtgggca ccggcagtcc tcgctactgg ggaggctgag gcaggagaat ggcgtgaacc 45720

tgggaggcag agcttgcagt gagccgagat agtgccattg ccttccagcc tgggcgacag 45780

agcgagactc cacctcaaaa aaaaaaaaaa aaaatagaga cccggaaagt taaaaatatg 45840

ataatcaata tttaaaaaca ctcaagagat gggctaaaga gttgacggaa caaatctaaa 45900

tattagattg gtgacctgca aaaccagccc aaggaacatc ccagaatgca gcccataaag 45960

ataaagagag catttccgct gggcacagtg gtatggcagg ggaattgcct gagtccaaga 46020

gttgcaggtc acattgaacc acaccattgc actccaggcc tgggcaacac agcaatactc 46080

tgtctcaaaa aaaaaaaaaa ttaaattaaa aaagacagaa tatttgagag aaaaaaatgc 46140

ttatttcaag aaacatgaaa gataaatcaa gatattctaa ttcccaagta agaataattc 46200

cagaagcaga aaatagaata gaggcaagga aacactcaaa acttctccag tgccatagaa 46260

atgtgtatta atctttagaa tgaaacggac taccaaatgc tgagcaggaa gaacaaaaga 46320

gatccactct taagccagtg tggtgcccaa gcgcagtggc tcatgcctgt aatcccagca 46380

ctttgggagg ccgaggcagg tggatcacct gaggtcagga gtttgagatc agtcaggcca 46440

acatggtgaa accctgtctg tactaaaaat acaaacatta gctgggtatg gtggtgcaca 46500

tctgtaatcc caactacttg ggaggctaag gcaggagaat cacttgaaac caggaggtgg 46560

aggttgtagt gagccgagat catgccacac tcccagcctg ggtgacagag caagattcca 46620

tctcaaaaaa aaaatccact cctagacaaa taatagttaa attttagaac accaaggaga 46680

aagaaaaaaa attgtaaagc ttcagagaaa ataaacatta actacaaaga aacgagagtc 46740

agacgcgtgc acttcttcct agataccagc agataaagca atatctccaa aattcagaag 46800

gttttaacgt agaatcctat acccagtcaa gaatattcac atggaaaagt gaaataaaaa 46860

acattgttta aacatgcaag ggttcagaaa gtttaccatt cacagaatcc ctgaaaacaa 46920

aaccaaataa tcacttaagg actcattaag aaaacaaatg aaataaaagc accaatgatg 46980

agtaaataat cagaaaaatt tacagtttac ctaaataact gtttatgcat aatgtatgaa 47040

aacccaaaaa tttaatatgg gacagaatta aaatcatgat aagattcttt tttgctttac 47100

tcatggagag ttcacataaa cagattatct tttaatagca agagaaaaaa atgtttagat 47160

atgtgtgaaa aactaagggt accaaaacag tgcaaattca tttatcatca ggaaaatcca 47220

aattaaaacc acagtatcca ccagaataac taaaaggtaa aagacagaaa ttaccaagag 47280

ttggcaagaa tgtggagcaa ccacatatac ttctggggta aataagttgg tgcaaccggt 47340

actgaaaact gtttgctagt atctactaaa accgagcaca tgcacagact acaaccaagc 47400

agttccactc ccagatacac actcaacaga aatgcacaca ctcactcaac aaaagacgtg 47460

tactagagtg ttcatgtact tactattcat aatagtccaa aaatgcaaac aaccaactgc 47520

caatcaaagt caaatgtata tctatattag ggatatatac aatggcatat acacagcaat 47580

gagaatgaaa tgaaccagct cggcacagtg gttcatgcct gtaatctcag cactttgggc 47640

gggtaaggca ggcagatcac ttgaggtcag aaatttgaga ctagcctggc caacacggtt 47700

aaaacctgtc cccactaaaa acacaaaaat tagccgggca tagtggttgc aggcctgtaa 47760

ttccagctac tcgggaggct gggttgggag aatcgtttga acccgaaagc cggaggtcgc 47820

agtgagcgga gatcgtgcca ctgcactcca gcctggacga tagagcaaga ctccgtctca 47880

aaaaaggaaa tcaaaaatat aaaataagat gacaggaata atccgcaaaa gatcagtaat 47940

caaaataaat ataaatgggc taaagctacc tattaaaaga caaagatttc acacccataa 48000

ggatagctac tatcaaaaaa agagagagaa taacagatgt tagcaaggat gtatggaaac 48060

tgaaattctc acgcattgct ggtgagaata taaaatggtt cagcctctgc ggaaaacact 48120

atgctgggtc atcaaaaaat taaaaataga agtactactt gatccaacaa ttctacttct 48180

gggtatatac ccaaataact gaaagcaggg tcttgaagag atatttgtac acccatgatc 48240

atggcagcat tattcataat agctatgatg tggaaccaac ataaatatcc tttgataaat 48300

atatggataa gcaaaatgtg gtgtatacat tcaatggaat attaattagc aataaaaatg 48360

aagaaaattc tgacacatgc tacaacatgg atgaaccttg agggcattac attaaatgaa 48420

ataagccagt tataaaaaga caaatactat atgaggtact atattagata ctcatgcaag 48480

gtacctaaaa taggcaaatt catagagaca aaaagcagaa tggtggttgc caggggctgc 48540

ggtaatggat acagagcttc aattttgtaa gatgaaaaaa ttctggagat tggttgcata 48600

acaatgtgca cacacttaac actggggaac tgtaaactta aaagtagtaa atggtaaaaa 48660

taaaaataat aaataataaa ttttatgtta ttttaccaca atatttatta aaagacaaag 48720

attaactaat taaacaaaat ccagccataa gctaatggta agagtaacaa ttaaagaaga 48780

cacagaaaat tgaaaatcag tgactagaaa aagatattcc atataaatgc taacaaaaag 48840

caagtacagc aatataaaga gaatgaacaa aaaaaaaatt aaataagatg gctcgtttat 48900

tcccaaaagg tacaattcac caagaagata caagaattgt gaacctttaa gcacataaaa 48960

cagcttcaaa aatacaacat ttaaagaaaa atatatatta aacatagaaa tagtacaaaa 49020

acccctacaa gaatcataat gggagtcttc aatacaactc tccatatcaa caggtcaaac 49080

agagaaaaaa aataagttaa ggatgcagaa aacctgaatt accatcaata aacttgagat 49140

taatatagaa ctgtataccc aatatactaa gagttcaggg aacagtcgtg actgacagtg 49200

gactgcaaat taatctgttc ttaatctttg tttttctttc agcactgtgg cagaatagag 49260

atcctaaaaa ccttccagct acaaaacatc tttttaaaaa tataaaaaaa tacaaaaata 49320

actctgaaat caatagaaga cacatggtga aaccaaaatt ctagaataca gggagaataa 49380

aggcattttc agatattaca aaaacagaaa attgatcatt gctgaagtaa tttctaaaga 49440

atgtacttga gggagaagaa aaatgttcca aagaaaagta tctgtgatac aagaaggaat 49500

ggaaagtgaa gaaatggtaa acaggtagat aaagctaata aatgttgacc tagaaaataa 49560

caaaaacaat agcaataatg tctcgttgga agggttgaag taaaaataca attaaggcca 49620

aatgtgaggt aagtggaatg aaagaattag aagtccttgc cttgttcaca ggactgatta 49680

aataaatgag ccaggttttc cattcaaaca gttaaaactt gaacaaaata aactcaaatt 49740

aagtagaaag ataaaaaaca gaaattaatg tcatagaaaa ataaaaaatc aatagaatta 49800

atcaataaat cctggttaat aaaagctggt tctttgaaag gattaataaa ataatcatta 49860

agcaagtctg atcaaaaaaa aagagaaaag gtaccaaaaa aagtactgta tcagaaagag 49920

aacatacaga tacatacaga tatgtaagag tctgttttct tacaccagaa tactatatac 49980

aacattatgc tagcatatat taaatttcaa taatgttaat gattttctag gaaaacagaa 50040

aatattaaat ttactttgaa gaaacagaaa aactgagaaa aataaatgat catgaaaaaa 50100

atgaaaaggt aattaaatac tgatattaac tgcctaaaca acaccagcag cagcccaggc 50160

agtctgcagt caagttctgc caaacttgag ggaacagata attcttctat tccagagcat 50220

agaaaatgat ggaaagtttc ccaatttaat cagagaggac agcctgatcc ttgttatgaa 50280

cacagataaa aatggggtaa actatatgcc aaactcagat accaaaaccc taaataagat 50340

gctagcttat tgatgtgaac aatccaaaag tgcattttaa attagcccag ggttttagag 50400

aaagaaaatc tagcaatgtg accaccactt atgttaacaa ttttaagacg aaaatctaca 50460

tgatcatatc aatgcatgct acacaaaagc atttgggcaa aaaacccaac acccaccctt 50520

gactttttaa actcttagta attaggcata aacagaaatg tacttaatgt gatagaatac 50580

actcggtgaa gatacagagg gaatgctccc taaaaccaag cccaagacaa agattcctat 50640

ttaacctcaa tagtcaacac tgcagcgaga gtaatctatg gaagacaagg aaaaaagtaa 50700

aaacatgaga gacatctgtt gtttaacaga caataagatc acctacttgg aagaggcaaa 50760

cgaatcaagc gaaaaactat taaaactgag acaggcttta gtatggaggc tcagcttcag 50820

ctgtagtttg ggctaccaaa ttcaactcgc ttgcttggag agttaatcct gcaaagctaa 50880

tttctgttga ggtattagga ttgacaagcc tgtgctcctc cctcctcccc catcttcaac 50940

actgaaataa cacggtgttt ggaactggat aacagaatct tccaaaaaca aaaattgtcc 51000

tgaagggctg acttgtgccc ttactcaaaa aacactttat ctgctgcctg cagctcctac 51060

agttgctggt ggataagcct gccaaccagc tcggcgtaat tcttcctgca gagggcaagg 51120

aagagcactt tcacaggaaa atttttttcc gaactgtatg ccgcttatta cataaactta 51180

cgtgctggca aatggagctc cagcaaaata agatattcag agtcaaactt ccttaggaaa 51240

aaaaaaaaaa aaaagcaagc acataacact aatttccttg catgggcact ggggaaggag 51300

gtcgttactt ccgcacgccc gcaggtccgc accaccggga aacccacggg caccgcgcgc 51360

tgcccccggg ccttccaggt gcactgcgcc gcggcgcccc agctgacccg ggatgcgcag 51420

ccctagccct tcccctgtca ccccggccag gaaggggcgg gagcgcggcg gacgccgagg 51480

gcgaagggct tctcggtcct ctgcaccacg cagcaccccc aaggcacaac agggagggtg 51540

cgggaggctc ccgagaccca ggagccgggg ccgggcgtgc ccgcgcacct gtcccactgc 51600

ggcgagggct ggggtcgcct ccagggccgc agctgtcggg agccacctgg ctctcagtcc 51660

cgggtccctg cgacaaccct cgggcccgga ggggaggagg cggccacctg ccgctgccac 51720

ctgcggcacc ggtcccaccg ctccgggccg ggcaggacag gccaggacgt ccctcctggg 51780

ctggggacag gacacgcgac gaggggaccg gggcccccgc ggcgaagacg cagcacgcct 51840

tcccagaaag gcagtcccgt gcccccacga cggactgccg gacccccgcg ctcgcccgcc 51900

catcccttca gaccacgcgg ctgaggcgca aagagccggc cggcgggcgg gctggcggcg 51960

cggctagtac tcaccggccc cgctggctca gcgccgccgc aacccccagc ggccacggct 52020

ccgggcgctc actgatgctc aggagaggga cccgcgctcc gccggcgcct ccagccatcg 52080

ccgccagggg gcgagcgcga gccgcgcggg gctcgctggg agatgtagta cccggaccgc 52140

cgcctgcgcc gtcctccttc agccggcggc cgggggcccc ctctctccca gctctcagtg 52200

tctcatctcc ctatctgctc atcctctggt cgcacataat cgatgtttgg gcgtcccaag 52260

ccagatgtgg accccatttc cgcactctac actggaggtt ttctaagggt ggtgcccgga 52320

ccagcagctt cagcctcatc tgggaacttg agaaaatgca gattctccgt cccacccagc 52380

ctattcggtt tttcctgcac taaaaccatg aaggtggggc ccagcagtcc acattctcgc 52440

aagcccgtca agtgattctg aggcgccctc cagtttgaga gctatgctca cggcctcacc 52500

tccgccccgc aaggagcccg gtcttgcctg tggcgctagc cgcacacgga cacctcatcc 52560

tgcggggccc gcccccccgc tgcaccctca ccgcccaacg cctcctccgg gatgcagcgg 52620

aggcgcctgg aagtcggcaa ggtcaacatc cccctcagca tcttccctac cctcacggct 52680

cctcctccag gggtgcctca tggccagggg ttagaaagag ccactgtgtt tcttgacatg 52740

gaagtggcct aagaccttaa tgaaaactgc aggagtggaa tgacagaacc tttggtcata 52800

cttgagggcg tgaagctcaa atgaggagga aggaaaggat ccagggagaa taaccaaccc 52860

tggcaagttg tggcgcccag gtagaggggc gagcctaggc tagcggttct cgaccagggc 52920

cggtgttgcc cctcctcgcc gccccgcgta catttgggga ggtctggaga catttttggt 52980

tgtcatgatg cgggagttgc tactgttgcc taagtgggta gacacgaggg tgctcctcaa 53040

catcctacct gaaggacagg actgccccac aaggaagaat gatccggccc caaataagaa 53100

accctgggct ggtcagcaac aacccctttg ttctgagaag agaggaggaa agaataaaag 53160

aagtggggtg aagttttggt ttggtagagg aaacttgaag acattttcac tggaaaggaa 53220

gagaggaaga ggagggagat gtctgtaagg acgagcaaac cgggtgacag ctgatttcct 53280

catattgaag taatgagtcc tagttataat aaattcctaa taaaaaccca gtttatccct 53340

gcaataaact tgtctttttt ttttaaatat actgcttgat tctgtttgct aatattttat 53400

ttacaggctt tgcattgata tgcaaaaatg agatgggcaa taattttctt tttgaatgtc 53460

taatgttgtt tggtttcaga atcaatgtta tgctcacatc ataaaaaatt tggaaccgag 53520

gcaggaggag tgcttgaggc cagaagttcg agaccagtct aggaaacaca gtgagacccc 53580

cccatctcta caaaaaaaaa aaaagaaaaa aaaatgggca tgtttgcttt ttccttttac 53640

tctgaacaat ttaaggagca ttaaaattat ctattctttg aggtttgatc atttcccagt 53700

taaaaatgtt cctcccagcc tgatgctttc tttggggagg gtaaatcttt taaggctaga 53760

aaagtttctt ctgtggcaat tttattattt acattttaaa aattattcta gagttaattt 53820

tgataaagca tgtatttctt aaaacaaatt atcctttttt tccagatgtt caagtgtatt 53880

tgcataaagt tgaggaaagt agtcttttgt gaatctttta acttctccca aatatcttat 53940

tttgtgtatt tttgcttctt tattttgtta acttttaaaa gtgtattttt ttttcaaaga 54000

atcagctctt aggtttatgt ttttggttat actggagctt ttttcttctt ctttttaaaa 54060

tattttttct cctttatttt ttagacgtat tttgatctaa cgtaatcgga agaaggtaaa 54120

ttagaatctt ttgttactat tgtgttttta tttctcctta tttctctgaa gtcctgcttt 54180

ataaatagta ccatgttatt tgtgcataaa tattcatttg tcttatattc ttgggaattt 54240

tcccacttca tcataaaatg accttccttg tctcatttaa tgtgttcaaa ctttgccctg 54300

aatttaactt tgtctgatat tttaccatcc tgctgaattt tgtttgttac cccaaacaac 54360

ctttgctgtt ttcgtctttt ctgaaccctt tattttaggt aatcccttga attagagcac 54420

taagttttgc tttgtgatta aatctgaaaa tctttatctt gccatagatg agttgagccc 54480

tattcatgtg acagctatat tatgctgttt catagccctt ttggtccttt tttcactctt 54540

gcattgcata ttttgtgttt attgtgtttt gtgtttcttc tgataatttg gaaggtttgt 54600

atttttattc agggagttgc cttataatca tactccgcaa tacacatcgt cctcagtttc 54660

ttcagactgt ctgttaactc cctattctga ataaaaatga cattgtaatt tccctctttt 54720

ttctttaccc cttttcttct cctcacctaa tgtaaatgat tttatccttc tttagtattt 54780

gcttttttaa ttaactacat ttataaatat ctttatcact tgatttttaa atcagctttg 54840

aatgagatat ttggattcct agatataaaa gatgttaatt ataccatttc cacgttagta 54900

ggtttataaa atcatacatt ctgctgtgta accataatcc cacgtttgtt ttagttccac 54960

tcctacagtt aaaagattca gaagtattat taacagttat tttgccatag ttttttcccc 55020

aacccatttt gtggtaagtt atgatcctgc tttagtttct taagaataat ttatagagca 55080

gagtgtggtg gctcacgttt gtaatcccag cactttggga gacaagaggt agaaggatcg 55140

cttgaagcca gcagttcaag accaccctga gcaacatagt gagaccttgt ctctacaaaa 55200

aattttaaaa tttagccaga cgtagtggcg tgtgcctata gtcccagcta ctcaggaggc 55260

tgaggcaaga ggattgctag agcccagaag tttgaggctg cagtgacctc tgattgtgcc 55320

actgcacccc agtctgggca agaaagtgag aacctatctc tttaaaataa caataataac 55380

ttatgaaaat tatattccct gagtttttca tgtttaaaaa tatttgttgc ctttatcctg 55440

taaaagtttg agtataaatt cttgggttat actttattta ttgaagaatg tataagtatt 55500

gtcttctaga attgagtgtt gctgtaatga aaccagaagt cagcctggtt tatttttcct 55560

cagaaatgag gtaattgccg gccggacacc gtggctcatg cctgtaatcc caacactttg 55620

ggaggccgag acaggtggat cacgaggtca ggagattgag accatcctgg ctaacatggt 55680

gaaaccccgg ctctactaaa agtacaaaaa gttagctggg catggtggtg gacgcctgta 55740

atcccagcta cccgggaggc tgaggcagga gaatggcgtg aacctgggag gaggagcttg 55800

cagagagctg agatcgcgcc actgcactcc agcctgggcg acagagtgag actccgtctc 55860

aaaaaaacaa aaaaaaaaca aagaagtgaa gtaattgcca tgatgctcca agaattatct 55920

ctttgtctat gaaatccaga aatctcactg ttatacattt tggaattatt attctgggcc 55980

aatatttcct gggacacaat agattgactc tatagattta attttttttt tttttttgag 56040

acagagtctc actgcaatct cagcttactg caacctctgc ctcacgggtt caagcaattc 56100

tcctgcctca gcctcccaag tagctgggac tacaggcgcg tggcaccatg cctggctaat 56160

ttttgtcttt ttagtagaga cagggtttca ccatgttggc caggctggtc ttgaacgcct 56220

aacctcaagt gatccacctg cctcagcctc ccaaagtgct gggattacag gcgtgagcca 56280

ccatgcccag cctcaattcc tctttctatc tggtaatttt tctgaagttg aaaacatttg 56340

ttctaatacg ttatttcagt gttcttctaa gatgtgtaaa gcaccctatt cccaggtcag 56400

cccccatctt gctagtgagc tcggctggtt cttcacaaga gctctggttt tctcctgctt 56460

aatctcaagt acctctgtca gcctccacct ggtttatgat ttggagtttt ttggtttttg 56520

ttttttgttt ttgacagagt cttactctgt cacccaggct ggagagcagt ggcataatct 56580

cagctcactg caacctctgt ctcccaggtt tgagcgattc tcctgcctca gcctactgag 56640

tagctgggat tacaggcgcg tgccaccaca cccggctaat ttttgtattt ttagtagaga 56700

tggggtttca ccatgttggc cagggtggtc ttgaactcct gacctcaggt aatccacctg 56760

cctcagcctc ccaaagtgct gagattacag gcgtgagcca ccgcgcctgg catggtttgg 56820

agttttaatc tgtagtttta ataaagatag tgcttatgtt tgtgtttctt atatttcttg 56880

gtactcttgg gtaatttgta agatccccat atctacacaa gaagtccatt ttcaattctt 56940

ttcttcagac tgtttatttt attttatttt attttatttt tatgtttgag atggagtctc 57000

gctgtgtcac ttctggaggc tggagtgcag tggcgcgatc tcaggtcact gcaacctccg 57060

tctcccgggt tcaagcaatt ctcctgcctc agcctcccga gtagctggga ttacaggcac 57120

ctgccacttt ttaatttttt tagagacaga gtctcgcttt gttgaccagg ctggagtgcg 57180

gtggtgcaat catggctgac tataacctcc aaatcctggg ctcaagtgat cctcctgcct 57240

cagcctcctg agtagctggg actacaggca catgccacca tgcccagtta attttaattt 57300

ttttgtagag acagggtctc catatgttgc ccaggctggc ctcctactcc tggcctcaag 57360

taatcctcct acctcagcct cccaaattac taggattata agcatgagcc accatgccca 57420

gccttgttct actactttaa tttcatatgt taggtgacca tgtaattgat catccaaacc 57480

aggatactgt aagaatgaaa gaggctgaca gtagtatgat gctgggacta gcattgtgca 57540

ctgagattat ttctgggaaa gcaggagata cggtcaccct acttatagtg tgcttgtctt 57600

tggattgttg aatttggagt ttctatttgc aggcttattt caactgggca gccttgatcc 57660

gccctgccca gcaatgctac cgttctctcc accgggtctc tgggacccct tcagtcacta 57720

tacttagctc agttccccac cctcccactc cctaaaagcg taaccaggaa tcctgcctca 57780

ggtctactgc cgtcttccgt gggctgtttc agttcctatt acccagagtc aaactcccag 57840

cattccctac ctgattccag acttggagtc cagagcttta acctcttcag gccaactccc 57900

cactttgcat ttctgtccct atatcttagt ccatggagat acatttcatg tctttgagtc 57960

tacttacaaa gtaaattttg ctgtttttta attttttttt tgagatggag tcttgccctg 58020

tcacccaggc tgtggtgcaa tgacgccatc tcggctcact gcaacctccg cctcctgggt 58080

tcaagcgatt catctgcctc agcctcccaa gtagctgtga ttacagacag gcaccaccac 58140

gcccagctaa ttttttttat cttttagtag agacagggtt tcaccatgtt ggccaggctg 58200

gtcttgaatt cctgacctcg tgatctgccc atctcggcct cccaaagtgc tgagattaca 58260

ggcgtgagcc actgtgccca gccaattttg ctttttttat atttcattgc tatatgttta 58320

gaggataagt ttacagtgct atatgcattc ccaaatatta gaccaaaaaa atctccaaaa 58380

aattagaaag aaaatccaaa aaatctcaaa aaataccaaa aagcaacaat ctcacagacc 58440

atactcactg acccccaata aaataaaatt agaaattaac cacaacttaa caaaataaag 58500

tactcaagtc agagaggaaa gaggaaataa acatcaaaat tacaaagtct aggcggtggc 58560

tcacgcctgt aatcccagca ctttgggagg ccaaggcggg cagatcacaa ggtcaggaat 58620

tcgagaccag cctggccaat atggtgaaac cccgtttcca ctaaaaatac aaaaattagc 58680

caggcatagt gatgtgtgcc tgtaatccag ccacttggga ggctgaggca ggagaatcac 58740

tgaacccagg gagacgaaga ttgcagtgag ccaaaatcgt gccactgcac ttcggcctgg 58800

gtgacaaagc gagactccat ctcaaaaaaa aaaaaattac aaactcttta gatagaaatt 58860

ttggtgtttt tttttgagac ggagtctcac tctgtcgcag aggctggagt gcagtgggac 58920

tatgtcagct caccgcaacc tccatctcct ggattcaagc aattctcctg tctcagcctc 58980

ccaagtagct aggattacag gcgcccacca ccagacccag ctagttttta tatttttagt 59040

agagatggtg tttcaccatg ttggccaggc tggtctcaaa ctcctgacct caagtgatcc 59100

acctgcttca gcctcccaaa gtgctcagat tacaggcgtg agccaccgca ccccacctag 59160

atagaaattt caacatgagg ccgggcacaa tggctcacgc ctgtaatctc agcacttcag 59220

gaggctgagg cgtgggagga tcacttgggc ccaggagttc aggaccagca tgggtgacag 59280

agacagaccc tgtctctatt tatttgaaaa aaaaaaaaaa aaagagagag agaaagaaat 59340

ttcaacatga aaagtatctc tcaaaccctt cgagatgttg gcaaaaagcg actcaaagga 59400

aaatgtatta ctgtgtgtga atttgcttga aaataagaaa gaggccgggt gtggtggcta 59460

acacctgtaa tcccaacact ctgggagtcc gaatcaagtg gatcatgagg tcaggagatc 59520

gagaccatcc tggctaacat ggtgaaaccc tgtctctact aaaaatacaa aaaattagct 59580

aggcgcggtg gctcatgcct gtaatcccag cactttggga ggctgaggca ggtggatcac 59640

ctgaggtcag gggtttgaga ccagcctggc ctacatggtg aaacctcgtc tcttctacaa 59700

atacaaaaat tagctgggcg tggtggtggg tgcctgtaat cccagctact cagaggctga 59760

ggcaggagaa tcgcttgaac ccgggaggcg gaggttgcgg tgagccgaga tcgcaccact 59820

acactccagc ctgggcaaca gcctgggtga cacagtgaga ctccatctca aaaaatacaa 59880

aaaattagct gggtgtggtg gcctgcgcct gtagtcccag ctacccggga ggctgaggca 59940

ggagaatgga gtgaacctgg gaggaggagc ttgcagtgag ccgagatccc accactgcac 60000

tccagcctgg gcgacagagc aagactcttg tctcaaaaaa aagaaaaaaa aaggaaaaaa 60060

gaaccctgat aataaagaaa ccaaatgttc aactctcaaa gctcggacac tttaaagaaa 60120

taattaataa aggcagaagt taaagggagg atgataaagc aatttttttt gttggttttt 60180

ttgagatgga gtcttgctct gtcacccagg ctggagtgca gtgatgcgat cttggctcac 60240

tgcaacctct gcctcccggg ttcaagcaat tctcctgcct cagcctcctg agtagctggt 60300

actacaggtg cgcgccacct ggcccagcta atttttgtat ttttattaga gacggggttt 60360

caccatattt gttaggctgg tctcaaactc ctgatctcag gtaatctgcc cacctcggcc 60420

tctcaaagtg ctgggattac aggcaggcgc caccgcgcct ggcctaaagc aaaatattgg 60480

ttctgtgcaa aaggtcaata aaaagagcaa acgtttacaa actggagcca gcacccattc 60540

agctcagtgt gtctggagaa aaaacaatct cgcttcagaa ttcatgatta cgcagccctt 60600

tttgcttcct aaaaatccta ctatgttgct gttgaccatt ctctctcttt ctctctctct 60660

tgctttctct ccagaaaagc tattcagaca ttctcctctt tcctcaaacc tccaacactt 60720

cctcctccat ccttagcctc agctgctgac ctcacttcta atcattgaga aaccaggaga 60780

agcatttaag agtgaacctc cgcctccccg cacgggcaaa accacccacc cacagaattg 60840

tgccccaatt ctgcgtcctc tcctctcacc atggatggac ggtccaggct ccgagccaaa 60900

gccaggcctc ccctggagct ctggatccac cacctgcagc ttctcaggca gggccccagc 60960

agctcccctg ctcccttgta ccatcaatcc ctcccctcac tgggtcactc ccaacaatat 61020

atatatttag tgatgtttct cccatgtggt aaaatcactt agcctctctc ctcccccagc 61080

tactatccta tttgtttctt tccattctct gcaaaacttc tcaaagcatt gtgtctatgt 61140

gctgactcca tttatcttct cccgttctct gctgagtcct tcccacagac tctcacccca 61200

gttactccat gaaatgacct ctgcactgcc acatccaatg gtgaatgttc agttcttaat 61260

tttattcagt ctttcagcag catttgacct ggccgatcac tccctcttct taaaaatact 61320

tttctcagcc aggcgtgatg gctcacacct gtaatcccaa cactttggga ggccaaggcg 61380

ggaggatcat gagagcccag gagttcaaga tcagcctggg caacatggca agaccctatc 61440

tctacaaaaa ctaaaaagta gccagtgtga tggcatgcac ctgtagtccc atctacttag 61500

gaggctgagg cagtaggatg acttgagcct gggaaatcaa ggctgcagtg agccatgatt 61560

gcaccactgc actccagcct gagtgacagc gagaccctgt ctcaaaaaga caaaatagga 61620

aacttttctc agcatattcc tctgattctc ctgctgcttc tgtctgcaca gattcagtct 61680

cctttgccgg ttcttcctca tcctcctgat ctcttgacct tgaagtgccc cagagtacag 61740

tctttttttt tttttttgag acgcagtctc gtctgtcacc caagctggag tgcaatggcg 61800

aggtctcagc tcatgcaacc tctgcctcct gggttcaagc gattctcctg cctcagcctc 61860

ccaagtagcc aggactacag gcacatgcca ccatgcccag caaattgttg tatttttagt 61920

agagacaggg ttttactata ttggccacgc tggtctcaaa ctcctgaact cgtgaaccac 61980

ccgcctcggc ctcccaaagt gctgagatta caggcatgag ccaccacacc cggcccagag 62040

tacagtcttt agacggcctc tctacctata cttgctcccc tcataaactc ctcctgcctc 62100

atggctttaa ataccatcgg tagactgatg actcccatat ttctcttttt tttttggaga 62160

cggagtctcg ctcagtcccc caggctggag tgcagtggcg cgatctcggc tcactgcaag 62220

ctccacctgc caagttcaca ccattctcct acctcagcct ctccagtagc tgggactaca 62280

ggcacccgcc accacgcctg gctaattttt ttgtattttt agtagagatg gggtttcacc 62340

atgttagcca ggatggtctc gatctcctga cctcgtgatc cgcccatctc ggcctcccaa 62400

agtgctggga ttataggtgt gagccaccgt gcccagccga tgactcccat atttctatct 62460

cttgctgtgt gggagttctc ctcagaactc catactcata aatccaactc tcataaatag 62520

tatctcaaat gggcaatatg ctcaaaagtc aattcctact tttctcccta aacttgcttt 62580

cctgcagtct ccaccatctt aatgtccaat ctaacattag gaggcaaaaa ctttgaagtc 62640

attcttgact cttctctatt acacacccta tccaatcttt ctgcagatcc agtcgacccc 62700

caaatccagt tagctctcat catctcccct gttaccccct ggtccaggcc atcttcctct 62760

ctcacctgaa tcactgcagc attctcctca ctggtctctt tggttctgtt ttcactccac 62820

cttagcatag tctccacaga gcagtcagag ggatcctttt aaagtgtaat tcccatcctg 62880

tccctgctct gctcaaaacc ctgtcgtgat tcccgtttta atctgtcaga ttaaaagcca 62940

gagtctttcc agtgacctac atgatctgcc tattatcacc tcccacttct ttccccttgc 63000

tcactccact ccagctctgc agctgtcctt tctgtttcct gaacagccca gattttgctt 63060

ctttagaacc tttgtatttg ctgtcccctc tgtctggaat gtttttccag gaagtcacct 63120

ggctctctcc tgcacttcct tcctgaccac catgtttaaa aatcactcaa acacacttca 63180

ggccggacat ggtggctcac gcctgtaatc ccagcacttt gggaggccaa ggtgggtgga 63240

tcacctgagg tcaggagttc gagaccagcc tggccaacat ggtgaaactt cgtctctact 63300

acaaatacaa atagtagcca ggtgtagtgg cacacacctg taatctcagc tactcaggag 63360

gctgaggcag gagaatcgct tgaacccaga aggcagagga ggtgcagtga gccaagatca 63420

cgccacaaca ccccagcctg ggtgacagag caagacccca tctcaaaaaa aaaaaaagaa 63480

aaaaaaatca cacaaacaca cttctcttca tattcctttt ccaagtttta tttttctcca 63540

gaatacttta cattgtttta atggaagttc tccgtttccc cccaactaga atggatactt 63600

cctgcaggta ggcactctag tcctcccatc caagtactaa ccaggctcaa ccctgcttag 63660

cttctgagag caggggagat caggcctgtt cagggtggta tggcccagga attttgattc 63720

tgttttattc attgctgttc tgttgattct cttttgttcc tcctcctagt gctgagaaca 63780

ctacttgtac ataataagca ttcaataaat atttgttgaa tgaatgactt gttgaatgaa 63840

ttaatctcag aaatgcagga ctggttctac attagaaaat ttttcaaggt cattctctgt 63900

tgtcgtaaca cattaagaga ggaaaatttt gtactctaaa tcatttgata aaatacatac 63960

tgatttctgt tttcaaaaac tcttagtggc tgggcgaggt ggctcacatc tataatccca 64020

gcattttggg aggacgaggt gggcggatca cttgaggtca ggagtttgag accagcctgg 64080

ccatcatggt gaaaccctat ctctactgaa aatagaaaaa ttagccgggt gtggtggcgc 64140

atgcctgtag tcccagctac ctgggaggct gaggcaggag aatggcttga acccgggagg 64200

cggaggttgc agtgagccaa gatcatgcca ttgcactcca gcctgggtaa cagagtgaga 64260

ctccatctca aaagaaaact cttagtgagt ttaggaatcc aaggaagacc ctcaaactaa 64320

atagataatc tagctaccag aagccttcag taaaccttaa cactccatgg tgaaacatta 64380

gaaacattcc tactaaaaga caggctaaga atgcctgcaa tcttcacggc tagtccaaga 64440

agtcaaaaag aagaaatgag cgctgattta aaaaaataaa caaacaaaaa actaccgatg 64500

cagaggctgg cagcaaggac tgaaggactg tacagtactt gcctggagca ggcggatggc 64560

cacacccctg cgaagcctgc tcagctggct gggggacgct ccagtgtgtg agtggcagga 64620

tgcagggtac ttcctctgcc agggagttgc actggggaga tcctccccca ctcacacttt 64680

ggcagctggg gctttggaat gtgacttagc ttctgtcaaa gggtcaatcc accctttgat 64740

atatgatgca aaggcgaaca tatgatgcaa aggtgagaga acagcccaaa ttaggacttt 64800

taccacagct gtggaggtgg acagcgacag tggtgggccc tggccagact tttcatgctc 64860

aaaggtggtg gttgttcttc ctacttcttg tccctccagg gcttcctttg cctgtgtgct 64920

gaacctgctt cttttaattt tttttaactt ttttaaattt ttaattgttt taattaaaac 64980

aaattttgaa aactgtctga acctgctttt gaaccctgct atgatttgaa tgtttgtccc 65040

ctgccaaact gattttgaaa cttaatctcc aaagtggcaa tattgagatg gggctttaag 65100

cagtgactgg atcatgagag ctctgacctc atgagtggat taatggatta atgagttgtc 65160

atgggagtgg catcagtggc tttataagag gaagaattaa gacctgagct agcatggtcg 65220

ccccttcacc atttgatatc ttacactgcc taggggctct gcagagagtc cccaccaaca 65280

agaaggctct caccagatac agctcctcaa ccttgtactt ctcagcctct gtaactgtaa 65340

gaaataaatg ccttttcttt atgaattacc cagtttcaga tattctgtta taaacaatag 65400

aaaacgaact aaggcaaact ctcatgattc tactgccatg ccattccaat aaactccctt 65460

tatgcttaag agagccagag ttggccaggc gtggtgactc acgcctgtaa ttccagcact 65520

ttgggaggcc gaggcaggtg gatcacaagg tcaggagatc gagaccatcc tggctaacac 65580

ggtgaaaccc cgtctctact aaaaatacaa aaaaattagc tgggcgtggt agtgggtgcc 65640

tgtagtccca gctactcggg aggctgaagc aggaggagaa tggcgtggac ccaggaggcg 65700

gagcttgcag tgagtcgaga tcgtgccact gcactccagc ctgggtgaca gaatgagact 65760

ccgtctcaaa aaaaaagaga gccagagttt atttctgttg cttgcaacca agaaatctgg 65820

ctggtgcact gaagtttcca taaataatag caatttaaag actctttcca agccaggcaa 65880

tgcctagcct tgtgtagtcc ttgtggtaat acattcattc attcatttgt tcaaccaact 65940

gtgctccaga gactaagaat acaaaaatgg gggccgggtg tggtggctca cacctataat 66000

cctagcactt tgggaggccg aggcaggtag atcacctgag gtcaggagtt cgagaccaac 66060

ctggccaaaa tggtgaaacc cctactctac taaaaataca aaaaattagc tgggggtggt 66120

ggcggacacc tgtaatccca gctactcgtg agactgaggc aggagaatca cttgaacccg 66180

ggaggcagag gttgcagtga gccgagatcg caccactgca ctccagcctg ggcaacaaga 66240

gcgaaactcc acctcgaaaa aaaaaaaaaa aaaaaaagag ggccggggct gggcgcagtg 66300

gctcacgcct gtaatcccag cactctggga ggccaaggca ggagaattac gaggtcagca 66360

gatcgagacc agcctgacca acatggtgaa accccatctc tactaaaaat acaaaaatta 66420

tccgggcgtg gtggcgcaca cctctagtcc cagctacttg ggaggctgag gcaggagaat 66480

cgcttgaacc cgggaggcag aggttgcagt gagccgaaat catgccactg cactccagcc 66540

tgggtgacag agtgagactc cgtctcaaaa aaaaaataaa aaaaaaaaaa gaattcaaaa 66600

attgtagagt tatagtgtgc ttctagttta gttgagagga catctgtcct tcaaggaagg 66660

ctagaatcta taccctgagt ccttactgaa atcaatccag cagtcaaaac atgggaccaa 66720

cgatcacagc agtaagatag gaagagcacc tttgtacatt tagctcatgt tgagataagc 66780

cactgacaga gctgaaggaa gctcacagtt ctgggttcca tcctttggca tttaaaaaga 66840

aaagtgctaa gaaaattcgg ttggtcacgg tggctcacgc ctgtaatccc aacactttga 66900

gaggccaagg caggcagatc acgaggtcag gagttcgaaa ccagcctggc caacatggtg 66960

aaaccccgtc tctactaaaa acagaaaaat tagccgggca tggtggcgca tgcctataat 67020

cccagctact caggaggctg aggcaggaga attgcttgaa cccgggaggg ggaggttgca 67080

gcgagtgaga gcaggccact gcactccagc ctgggagaca gagcaagact ctgtctcaaa 67140

aaaaaaaaag aaaaaaagaa agaaaggaaa aaaagaaaga aaaaaaaaga aaaaagaaaa 67200

ttcaggccag gccaggcctg gtggctcaca cctgtaatcc caacactttg ggaggctgaa 67260

gcgagacggt gccttagccc aggagtttga gaccagcctg agcaacatag cgagaccctg 67320

tctctataaa aaaaaatttt tttttggcca gacgcagtgg ctcacgcctg taatcccagc 67380

actttgggag gccgaggcag gtggatcacg aggtcaggag atggagacca tcctggctaa 67440

cacggtgaaa ccccatctct actaaaaaat acaaaaaatt aaccgggcgt ggtggcgggc 67500

gcctgtagtc ccagctactc gggaggctga ggcaggagaa tggcgtgaac ccgggaggcg 67560

gagcttgcag tgagccgaga ttgcgccact gcactccaga ctgggagaga gtgagactcc 67620

gtctcaaaaa aaaaaaaaaa aaaaaaaaat taattgtcag gtgtgctggc atgcagctgt 67680

agtcctagct actcgggagg ctgaggtaag aagatcgctt gagcccagga gttcaaggct 67740

gcagtaatag tgcctctcac tctaccctgg gtgacaatga gaccctctct caaaaagaaa 67800

gaaaaaaggg aaagaagaaa agaaagaaag aaagagaaga aaggaaggaa gaaagaaaga 67860

aaaagaaaag gaaggaagga agaagaaaaa aaaagaaaga aagaaaagag agagaagttc 67920

aaagaccaaa gggtcaggat cccaaaatag tttttatgtt ttatttattt atttacttat 67980

ttatttttga gacagtatgg ctctgtcgcc caggctggag tgcagtgatg cgattgcggc 68040

tcactgcagc ctccaaactg ggctcaggtg gccctcccac ctcagcctcc cgagtagctg 68100

ggaccacagg cgcgtgccac catgcccagc taatttttta attctttgta gagatgaggt 68160

ctctatatgc tgcccaggct ggtctcgagc tcctgggctt aagccatcca cccgcctggg 68220

cctcccaaag tgctgggatt acagaagtga gccaccgcgc ctaatcgggt ggtttgtttg 68280

tttattgacg gggtctcgct gctgcccagg ctggagtgcc agtggctgtt cacaggtgca 68340

gtcctggagc attgcatcag ctcttgggct ctagcgatcc tccagagtag ctgcagctgg 68400

gattccaggc gcgccaccgc gcggggctca gaatgggttt ttatattgag ggttatgctg 68460

ccacctagag gatatatgta gtaccgaact gtgtgcgcag ggaggctgag gttgcagtga 68520

gccaagatga tgccagggca ctccagcgtg ggtgacagag caagatttca tctcaaaaaa 68580

aaaaaaaaaa aaaaaaaaaa aagaattgaa agtaaggtct tgaagagata tttgtgcctg 68640

tatggtcata gcagtattaa ctttgaccca ctagctaaaa cacaaaagca acatgtgtct 68700

gtcagcaggt gaacggataa acaaaatgtg gtatatatgt acaattgaat attattcagc 68760

ctttaaaaag gaataaaagg ctggatgcgg gggctcacgc ctgtaatcct aacactttgg 68820

gagactgagg tgggtggatc acccgaggtt aggagtttga gaacagcctg gccaacatgg 68880

tgaaacttca tctctactaa aaatactaaa attagccggg catggtggca cttgtctgta 68940

atccaagcta ctggggaggc taaggcagga gaattgcttg aactcaggag ccggaggttg 69000

cagtgagcta agatggcacc actgcactcc agcctgggca acagagtgag actccatctc 69060

aaaacaaaca aacaaaaaat tattatttcc aaagaaacaa gaccctgggt ccatttccca 69120

gcccacacct gatgttgact cacaacacac agcctggttt gctatgagcc tgcttcattt 69180

aattgtcacc ttaacttcac atcaccctca agtcctggaa taactctttg ctgacctttg 69240

tgtgctgagc catctccatg tcgctcaacg tgcagtccct ctcactgcac tgagtcaata 69300

gccagacgtg gtctgactgc agggtcatcc ttggtggctt aggctgactc gggcatagca 69360

gggtgctctg agacctcacc gcatataggc tttgccccca ataaactcta tataatattc 69420

atattatgtg gtctgggtgt gtgtagcttt gcactgtctt ctcgtgacag tgccctcaac 69480

ctctttccca ggatttcctc ctctacctcc tcaagtccca ctgctctgca aagaccaaaa 69540

gctgcagagt cccagctccc tcctttacac cccacgacgc agcctcctct ctcagaaccc 69600

tttaaacaga gtcttttact gcagatccca agaacagcca cacccctctc tcccacccac 69660

tccagacaca cccaggtaat tatagcaccc agggtaacta tgtagatgga gtccctggaa 69720

catgtggata gtgccccctg ggagtatgca aaagcaacat tgctggcacc tgcagagaac 69780

agggtgacat ccaggaatca gagcatgggc ctctgggagg tagggatgtg gccaggcagg 69840

ctgccaaaaa ttggtagagc aaggccacag gatctttctg accttccttc caaacagagg 69900

ctcctgtact ggtgatccct gtgttgattg accactccct tcctgggggt cgtggtctct 69960

gtcccagttg cccggacttc tgtgagtgtc ctactgaggt ccttttcatg agaagcatgc 70020

tgtccttcca cctgctggga gcaagagtga caacttcaat actataatag cagtggcata 70080

cagagaagaa gaaagatgaa gtggcaagaa aaacaggctt ccaagcagga gtttttctat 70140

aaaaacaaaa acgtttacaa gcaaactttt tataaagggc tagatagtaa atattttagg 70200

ctttgagagc cacatagact tgtttgcagg gactcaatgt cgctattgta gtttgaaagc 70260

agccatcagg gttatgtaaa tgagtgagtc tgattttgtt tcagcaaaat tttatttacc 70320

aaaacagaca atgagtgggc tggatttggc ccatgatcct tagtttgcca actcctgctt 70380

tgggctcacc cagatctgat tttgaattct ggctctgcta ctggttagct gcaggagctt 70440

ggaaggctct ctgagcctgt ttcctcatct gtaaaattaa agcaataatt tctaacactc 70500

aagagtgtta cctcacgcct gtaatcccag cactttggag gctgaggcag gcggatcacc 70560

tgaggtcaga agttcaagac cagcgtggcc aacgtggcaa aaccctgtct ctactaaaaa 70620

atacaaaaag tagccgggca tggtggcgcg catctgtaat cccagctact tgggaggctg 70680

aggcagggat actgctagaa cctgggaggt ggagcgtgca gtgagtggag atcacacctc 70740

cacactccag cctggccgac agagcgagac tccatctcaa aaaaaaaaaa aaaaagagtg 70800

ttagaaggtt ttgagataat gaataaaaga tgccttgtgt atactaagta ttcaacaact 70860

gatagctgca ttggtctaat tataacagtt tagaagcgat tgagtcaaca aatgctggat 70920

ttgtcaggga ggacttccta tcaggaggta gatcttgggc tgagtcctga agcaaagata 70980

ggcattggat agaggagttg agagaacacc ctaggactgt tattattatt attcgacacg 71040

gagtctcttg ctctgtcacc caggctggag tgcagtggcg cgatctcggc tcactgcaac 71100

ctctgcctcc caggttcaag cgattctcct gcctcctaag tagctgagac tacaggtgtg 71160

tgccaccaca cccggctaat ttttatattt ttagtagaga cagagtttca ccatgttggc 71220

catgctggtc tcgaactcct gacttcaggt gatccacccg cctcagcctc ccaaagtgct 71280

ggaataacag atgtgagcca ccgcacccag cccagaacca tttttcaatc cttggctctg 71340

ccttttatta gctgcaagat ctcaggcaat ttatttaacc tctccaaaga ctcattttct 71400

cattcacaaa atgaggcaaa taataatatc tactatccca ggttgtcatg agaattaaat 71460

gcaacatgac atttaatgaa atgagaagtc ccttggacat taactggcta aagtatgtgc 71520

tcgacaagga tatcatttta ggtggatact tagcatctca gaactgatgc tcacaatgga 71580

atatcattga aacgcattaa aattcatttt aaatgattgt aggtagtgag gcaattgaaa 71640

gaagaagaca agaggactga ttataatgct tcaggctcac tagtctcctt ttaggaggga 71700

aaaacaattt caagttaaat tttaggctct agatttttac ccctgctgct cattagaatc 71760

acccagattg atgaaatcag agcccatctg aggctgtgtt tttcatctcc agaatgagag 71820

ctgttgtggg gattaagttt ttgaaaaagt acatctaaca ggtgatcgaa aatgatagtg 71880

atattattgc agtgatggtc attattgttg ttattattat actgaaagag gcttcagttt 71940

tctgatccat aaagtgaggg aattgcatga gaccattgct aagattcctt ctagctctgt 72000

ttttttgttt ttgtttttta gacagagtct ctgtcgccca ggctggagtg caatggcatg 72060

atcttggctc actgcaacct ccgcctcccg ggttcaaatg atcctcctgt ctcagcctcc 72120

gaagtagctg ggactacagg cacacaccac catgcccagc taacttttat atttttaata 72180

gaggtggggt ttcaccatat tggtcaggct ggtctcaaac tcctgacctc aggtgatcca 72240

cccgcctcgg cctcccaaca tgctgggatt acaggcatga gccactgtgc ccaacccctt 72300

ctagctttct tgatcactga ttctagggtt ctctgctgaa atatatttga gacatcctgg 72360

ataaaagatc atgcaagagc tcccaatatg gtattaataa ttgattctgg aggcttagct 72420

actcctgatg gattagacat gactcaactg cctctcttat gtgtacaaca caacaacaca 72480

accaagaaag gttattctgg cattccattt attcagttta tttacagccc ttacttccag 72540

cagcacgtta aagatatggc cagggccggg tgcagtggct caagtctgta atcccaggac 72600

tttgggaggc caaggtgggc ggatcacaag gtcaggagtt tgagaatctg gcaattcttc 72660

agacttagaa gcaaccagct cgataacaca gtcttgtgtg ggctctccct ctgtccctcc 72720

ctcgcttccc tcatttctca tccctgcccc tgagactgtg caccttcaca tagccctgcc 72780

atgagacctt catctcaggc tttgctttct ggggtaactg aggctaaaca ctgagtggcc 72840

ctaaaagagg attgggattt ggaagttaga ttattcacca gagaacagac tttgctgatg 72900

atcaggccca ggttgtaatt gttgaaaaaa agagaggatg catagtctta tctcatctcc 72960

tagtcaaagt caacaccatg ataaataaga gtcaaatcct gagatgtgaa ttggggacat 73020

ttgagtggtt aaccctgaga agcttgcacc ttcagacccc tcaatacccc tgctccccag 73080

agaaggctgg acattgacct cagcacaggc aggagccctg caagatgcca tttgtcctac 73140

taaagatgga cccctccact ctgtttctag gtaaataacc aaagtcaagt ctccacacag 73200

cctgagcaag aaagtcagag cctgctacag gagaaaatac cacactggcc aaaggattca 73260

ctagccctgg ccactgtgtg tgggaggaac cagggaatca tgtgtgggag tcaatgttga 73320

agctgttgga ctgggggtgg ggtggaatat aagcctggcc ctggggagtt tttcccgttt 73380

gagggccttt acccacaact caagatccag tgctatagca ggagatccca gagctagtcc 73440

taacagatgg tcaggattga acttggccta gagtaaaatg aggaggatag tgccagaact 73500

ttctcaacat actattgagg aagaggtcag aaggcttaag gaggtagtgt aactggaaag 73560

gggtcctgat ccagacccca ggagagggtt cttggacctt gcataagaaa gagttcgaga 73620

cgagtccacc cagtaaagtg aaagcaattt tattaaagaa gaaacagaaa aatggctact 73680

ccatagagca gcgacatggg ctgcttaact gagtgttctt atgattattt cttgattcta 73740

tgctaaacaa agggtggatt atttgtgagg tttccaggaa aggggcaggg atttcccaga 73800

actgatggat ccccccactt ttagaccata tagagtaact tcctgacgtt gccatggcgt 73860

ttgtaaactg tcatggccct ggagggaatg tcttttagca tgttaatgta ttataatgtg 73920

tataatgagc agtgaggacg gccagaggtc gctttcatca ccatcttggt tttggtgggt 73980

tttggccggc ttctttatca catcctgttt tatgagcagg gtctttatga cctataactt 74040

ctcctgccga cctcctatct cctcctgtga ctaagaatgc agcctagcag gtctcagcct 74100

cattttacca tggagtcgct ctgattccaa tgcctctgac agcaggaatg ttggaattga 74160

attactatgc aagacctgag aagccattgg aggacacagc cttcattagg acactggcat 74220

ctgtgacagg ctgggtggtg gtaattgtct gttggccagt gtggactgtg ggagatgcta 74280

ctactgtaag atatgacaag gtttctcttc aaacaggctg atccgcttct tattctctaa 74340

ttccaagtac caccccccgc ctttcttctc cttttccttc tttctgattt tactacatgc 74400

ccaggcatgc tacggcccca gctcacattc ctttccttat ttaaaaatgg actggggctg 74460

ggcgcggtgg ctcatgcctg taatcccagc actttgggag gccgaggcgg gcggatcatg 74520

aggtcaggag atcgagacca tcctggctaa cacggtgaaa ccccgtctct actaaaaatg 74580

caaaaacatt agccaggcgt ggttgcaggt gcctgcagtc ccagcggctc aggaggctga 74640

ggcaggagaa tggcgtgaac ctgggaggtg gaggttgcaa tgagccgaga ttgtgccact 74700

gcactccagc ctgggtgaca gagcgagact ccgtctcaaa aaaaaaaaaa aaaaaaaaaa 74760

tagctgggca tggtggcgcg tgcctgtaat accagctact ctggaggctg aggcaagaga 74820

atcgcttgaa cccagtaggc ggaagttgca gtgagccgag atcttgacac tgcactccag 74880

cctggtgaca gagtgagact ctgtctcaaa aaaaaaaaaa agaaaaaaaa agacagaaag 74940

aaagagcaca gacagagtca caggtatttg cagtaggaag ctgtcaggtt agagtgcacg 75000

gaaatagaaa gtatatttta cacttacagc acatcttcgt ttgattagcc acatttaaaa 75060

tactgaatag caacgtgtgg ctatttagta ttcactaaaa tcttggacag tgcaagtcta 75120

aagaatcctt gatccgtccg gcatggtggc tcacgccttt aatcccagca ctttgggagg 75180

ccaaggtgga aggatcactt aaggtcagga gttcgagacc agcctggcca acatggtgaa 75240

acctcgtctc tactaataat acaaaaaaaa ttagccgggc atggtggtgc atgcctgtaa 75300

tcccaggtac ttgggaggct gaggcaggag aatagcttga atccaggagg cgctgcagtg 75360

agccgagatc atgccatgcc actactgcac tccagcctgg gcaacagagt gagactgtct 75420

caaaaaaaaa aaaaaaattg ttgggcgtgg tggctcacgc ctgtaatccc agcactttgg 75480

gaggctgagg ggggtggatc acctgggttc tggagttcga gaccagcctg gccaacatgg 75540

tgaaacccca tctctactaa aaatacaaaa attagctggg cgtggtggtg ggcacctgaa 75600

atctcagcta ctcaggaggc tgaggcagga gaatttcttg aacccaggag gcagaggttg 75660

cagtgagcca agatcgcgcc tctgcactcc atcctgggtg gcagagcaag actatgtctc 75720

aaaaaaaaaa aaaaaaatac ttgattgtct ggacattctg cagaacatca tatggagaca 75780

ctatgttgac gacatcatgc tgattgtaag caagaaatgg caagtgttcc agaaacacag 75840

tcaagacaca tacatgccag aaggtgagat ataaactcta ctaagattca gtggcctgcc 75900

acactggtga catttttaaa cctgctagat gtttgtgtag aaaaggattt aaccttgccc 75960

aaagaggggt ctggcctttg tccccagcta ctggacataa tctctttaaa ctcttgaaat 76020

atcattcctg atagaagtat ttttgttttg actaggggcc ttgggccagc cagatagcaa 76080

caatgtgatc tgggttgggg gctttggatc aggtggcatc agtgtgacct cctgagtggc 76140

tagagactag aatcaaccac atgggcagac aacccagctt acatgatgga attccaataa 76200

agactttgga cacaagggct tgggtaagct ttcctggttg gcaatgctct atactgggaa 76260

acccattctg actccatagg gagaggacaa ctggatattc tcatttggta cctccctggg 76320

ctttgcccta tgcatttttc ccttgtctga ttattattat tattatgaga tggaatctcg 76380

ctctgtcacc caggctggag tgcagtggaa tgatctcaac tcactgcaac ctctgcctcc 76440

ccggttcaag cgattttcct gtctcggcct cccgagtagc tgggactaca gatgcatacc 76500

accacacccg gctaattttt ttgtattttt agtagagacg gggtttcacg ttagccagga 76560

tggtctcgat ctcctgacct catgttccgc ctgcctcggc ctctcaaagt gctaggaata 76620

catgtgtgag ccaccgcgcc cagccccctt ggctgattat taaagtgtat ccttgagctg 76680

tagtaaatta taaccgtgaa tataacagct tttagtgagt tttgtgagca cttctagcaa 76740

attatcaaac ctaaggatag ccttggggac ccctgaactt gcagttggtg tcagaaataa 76800

gggtgctcat gtgtgtacca tgccctctaa ttttgtagtt aattaacttt cacaacttta 76860

ttattaccgc ttacactcaa tgtttattca catttatcca cataccactt attctagtgc 76920

cttgcatcaa agactttcta tctcatgtac tttattctgc ttgaagtaaa tcctttagga 76980

tattcttttt tttttttaaa ctttgcacat acatactttt attttttatt tatttttaat 77040

tttgttattt ttgtgggtac gtagtagata tatgtattta tggagtacat gagatgtttt 77100

gatacaggca tgcaatgtga aataagcaca tcatggagaa tggggtatcc atcctctcaa 77160

gcaatttatc cttcaagtta caaacaatcc aattacactc tttaagttat tttaaaatgt 77220

acatttaatt ttgtattgac tagagtcact ctgttgtgct atcaaatata attttttttt 77280

tttttgagac agagtctcac tcagtggccc agactgaaag tgcagtggca caagctcggc 77340

tcacttcaat ctctgcctcc ctggttcaag cgaatctcct gcctcagcct cccacatagc 77400

tgggattaca ggcacacacc accatgccca gctaattttt atattttttt agtagagacg 77460

ggttttcgcc atgttggcca ggctggtctt gaactcctgg cctcaaatga tctgaccacc 77520

tcagcctccc aaagtgctag gattacaggc atgagccacc acacctggcc aaaatagaat 77580

attctttagt gaggtctgct ggtgacaatt tttttctttt ttttgagact gagtctcgct 77640

gttgtcagct tgggctggag tgcaatagca cgatctcagc tcactgcaac ctccacctcc 77700

cggattccag caattctcct gcctcagcct cccaagtagc tgagagatta caggcaccca 77760

ccaccacacg cggctaattt ttgtattttt agtagaaatg ggggttcacc gtgttggcca 77820

ggctggtctc gaactcctga cctcaggtga tccacccacc ttggcctccc aaagtgctgg 77880

gattacaagc atgagccacc acgcacagcc aattttttcc gtttttgtct gaaatcttat 77940

tttgtgtcat ctttgaaata tatttttgat ggatataaaa ttgttggttg atagttatta 78000

tcattattat tattattttg agacagggtc tcactctgtt gcctatgctg gggtgtagta 78060

atgtgatctc ggttcactgc agacttgacc tcctagggct caggtgatct tcccacctca 78120

gcctccctag tagctgggac tacagatgca tgccaccata cccaactaat ttttctattt 78180

tttgtagaga tgaggctttg ccacatttcc caggctggtc tctaactcct gagctctagc 78240

aatccaccca ccttggcctt acaaagtgct gggccatgac tagccagcag ttacttttta 78300

tagcatattg aatatttaat atgaatcttc tggcatccac tgtaactgtt taaaaaatca 78360

gctgtttact tggcactctt tttttttttt ttttttttga gacagagtct tgccctgtcg 78420

cccaggctgg agtgcagtgg cgtgatcttg gctcactgca agctctgcct cccgggttca 78480

cgccattctc ctgcctcagc ctccggagta gctgggacta aaggcgcccg ccaccacgcc 78540

cggctgattt ttttgtattt ttcgtagagt tggggtttca ccgtgttagc caggatggtc 78600

tcgatctcct gacctcgtga tctgtccgcc tcggcctccc aaagtgctgg gattataggc 78660

gtgagccacc gcgcccagcc tctttttttt ttttttttag acggagtctt actctgtcat 78720

ctaggctggt gtacagtggc gtgatctcag ctcagtgcaa cctccacctc ctgcctcagc 78780

ctgccaaata gctgggatta caggtgcgta ccatcacgcc cggctaattt ttgtattttc 78840

agtagagatg gggtttcacc atgttagaca ggctggtctc gaactcctgg cctcaagtga 78900

tctgcctgcc ccagcctccc aaagattaca ggcatgagcc accgcacccg gccaagtagc 78960

actcctttga aggtaatctg cttcccctac ccctagcaat ttttaacaat ttttcttcat 79020

ttttatttcc tgaagttttg ttattaataa tctgtgtgca gatttctttg tatttctttt 79080

gtttgcagtt catagtgatt cttgaattag tgtgttggtt tctgttatca ccacaggaaa 79140

attgtcagcc gttagctttt caaatatttc cttgctaaat tctctcttct cccctttcgg 79200

tacaattgat ttgattaaaa ctaaaaccag ggccgggtgc agtgactcat gcctgtaatc 79260

ccaacacttt gagaggctga ggcaggtgga tcacctaagc tcaggagttc aagaccagcc 79320

tggccaatat ggtgaaaccc cgtctctact aaaaatacaa aaattaccag gcatggtggc 79380

acacatttgt agtcaggagg ctgaggcagg agaattgctt gaatccagga ggtggaggtt 79440

gcagtgagct gagatcccac cactgcagtc tggcctgggc gacagagtga gatgagaatc 79500

tgtctcgaaa aaaaaagtta tgaatgtttg ataaactata tttgttagaa tgtttgttgt 79560

agaatactat tcattgattt ttaaacaatg ttagattaaa ccattcactg gatttgtgat 79620

aattaactta ctgattttac ctcactgatt tgttgtaatt aatacaactg gtataaaaag 79680

actgtgacga ggccgggcat ggtggctccc gcctataatc ccagcacttt gggaggctga 79740

ggcaggcgga tcacctgagg tcaggagttc aagaccagcc tgaccaacat ggtgaaaccc 79800

catctttact aaaaatacaa aattagccgg tcgtggtggt gcatgcctgt aatcccagct 79860

cttcgggagg ctgtggcagg agaatcactt gaacccggga ggtggaggtt gcagtgagcc 79920

gatatcgcgc cattgcactc cagcctgggc aacaagagcg aaactccgtc taaaaaaaaa 79980

aaagaaaaaa aacacataaa acaaaacaac actgtgacgg ttcccaaaaa ttaggagcat 80040

aattaaagga actcctgata aaaattaatt ttatcttaca tgtaaactaa aatgacttta 80100

tgaagttaat tcagaaatac aatgcagggt attagtttgc cacagctgcg tattcagcct 80160

aatgtaatat tcttgttatt tttaaattct tcttttaact ttactcatat gtggatcatc 80220

aaatttcaaa agattaaatg acaatactct tagcagcaag cttccctaag catataaaca 80280

ttttaatggg tgatgattca gaaggtaccc gaagaatatg tactgccaga tatcattcac 80340

ccccatatac ctgcccgaca gacatcccat tttgggaccc tggataaatg tgtgggtgga 80400

gagaaagata ggagaaagtg gtataagcaa atggctttgg agtctgattg acagcgattg 80460

aaatcctgtc tctacctctt aacagcctca tgatcctaca taagttaccc cgatcctcag 80520

ggccacatct gtaaattggg ggttgcgatg gcagccatct cacagggtct cttttcgggg 80580

aagggcagga attatggatt aagtgagcta gtaattgtaa agcacttaat acaaggaggg 80640

cgcataataa gtacttcata aataatgacg gccattatca tgactgaggt gtatgcagct 80700

gtcggggatt acggcgactt cagaatttct ggtgggcagg gctcaaaggc agcaaatcac 80760

actggaagtc gaggtgaggc actgcttctg cacagactgc ttagctggag agaatgagga 80820

aggcttagag gagatttaga ggaacttaga gtcctccgcc tccaactctg tgggatctgc 80880

tcccgtgcca gagacattca ggggatttct cgcactctcc cctcccctac gtccctcccg 80940

ccccatccaa ctaaccacac aacacataca aaatagcccc tgcgaggttc tgcacgctgg 81000

aagggaacag gagaagggcg ctgcgctttc ttgctgatgc cctgtacttg ggcccctggt 81060

agacacagcc acttgtcccc tcagcctgca gagaaatccc acgtagaccg cgcccgggtc 81120

cttggcttca gccaatctcc ctttggtggg ggtgggatgc acgatccaag gttttattgg 81180

ctacagacag cggggtgtgg tccgccaaga acacagattg gctcccgagg gcatctcgga 81240

tccctggtgg ggcgccgctc agcctcccgg tgcaggcccg gccgaggcca ggaggaagcg 81300

gccagaccgc gtccattcgg cgccagctca ctccggacgt ccggagcctc tgccagcgct 81360

gcttccgtcc agtgcgcctg gacgcgctgt ccttaactgg agaaaggctt caccttgaaa 81420

tccaggcttc atccctagtt agcgtgtgac cttgagcagt tgactttatt tttcagtgcc 81480

tagttttcca gataccagga ctgactccaa ggactattac tcatctggag ggtttagcac 81540

agtaccgtcg catagtaaat ttccatgtca gttttggtta cctttcatgc acttgcaaac 81600

atgccatgct ctgaaacgaa ataggcacat cttttttttt ttttttttta aggagtcttc 81660

ctctcgccca ggctggagtg cagtggcgcg atcttggctc actgcaacct ccacctcccg 81720

tgttcgagat tctcctgcct cagcctcctg attagctggg actacaggca tgccacgacg 81780

cccagttaat ttttgtattt ttagtagaga cggggtttcg ccatcttggc caggctggtc 81840

taactcctga cctcaggtga tctgactgcc tcagcctctc aaagtgttgg gattacaggc 81900

ataagccact gcatctggcc agaaatgaaa taagtaaatc ttttaacctg ctctaacaat 81960

atagtgaaaa gaccatatta ttattagagc aggttaaggg atttgcctat ttcgggttct 82020

agttatagtc ttaaacttgg acattcttgt agaaagtaaa aagtttcctc ttcaaagttc 82080

cccttcttgt taaagaatac atcataagtg ttagaagtaa tagtttattt taaagactaa 82140

ctttcttcaa gcctccttgc tttgtgctaa taactctttg ttaagcccta tcctatgtaa 82200

ctgttggaca tgctcacagg cacgttccag ttcacagcct atgccccttc cttatttgga 82260

aatgttattg cttccttaaa cctttcggta agcaacttcc tctccttctt cgttcttcct 82320

tgcacttacc tatttagaaa gttttaggct attagcaaat cggctatcag tttaagagtg 82380

tgaggtcccg ctccagccaa tggatgcagg acatagcagt gaggacgacc caaatgcgta 82440

agggataaat atgtttgctt ttcctttgtt caggtgtgct ctcgacatcg ttccatctgc 82500

gattgagcac cctttctgca gaaagtaaag attgccttgc tggagatctt ttgtctccgt 82560

gctgactttt cttcgtggca ccgattatct atttctaaca attttggtat ttctaacatt 82620

ctgaacaatc ttgggctagt tgtctcttct gggcctgttt ccccatccgt cacatgataa 82680

acttcattgg tttaaaaacc ccagcgaaca tttattgagt tactattacc ttcctgccct 82740

ccccaacccc aaccccaggg agcagttaca acctcagccg ctgagcgcac tcgccgggtg 82800

ttaagaagca ccaaagacag ggaggcttga ttgattttgc tttgggagta gagggtcaga 82860

agattcacag gaaaatggca tttgagcaag gatgattcac tggagctagc ttttaaatac 82920

tggcgaggct tttatgttgc agtcccttac aaagttgagc attcgcaggg actgcactcc 82980

gaaataagcc cgcttcccct tttcattcgc taatgatcca gggagctgct ggttccgcat 83040

gcggcaggtt gtgccttttc ctaatcaggg ttctgcatcg cctcgaaccc gcaggccgtg 83100

gcgggttctc ctgaggaagc agggactggg gtgcagggtg aagctgctcg tgccggccag 83160

cgcctgtgag caaaactcaa acggaggagc aggaggggtc gagctggagc gtggcagggt 83220

tgaccctgcc ttttagaagg gcacaatttg aagggtaccc aggggccgga agccggggac 83280

ctaaggcccg ccccgttcca gctgctggga gggctcccgc cccagggagt tagttttgca 83340

gagactgggt ctgcagcgct ccaccggggg ccggcgacag acgccacaaa acagctgcag 83400

gaacggtggc tcgctccagg cacccagggc ccgggaaaga ggcgcgggta gcacgcgcgg 83460

gtcacgtggg cgatgcgggc gtgcgcccct gcacccgcgg gagggggatg gggaaaaggg 83520

gcggggccgg cgcttgacct cccgtgaagc ctagcgcggg gaaggaccgg aactccgggc 83580

gggcggcttg ttgataatat ggcggctgga gctgcctggg catcccgagg aggcggtggg 83640

gcccactccc ggaagaaggg tcccttttcg cgctagtgca gcggcccctc tggacccgga 83700

agtccgggcc ggttgctgaa tgaggggagc cgggccctcc ccgcgccagt ccccccgcac 83760

cctccgtccc gacccgggcc ccgccatgtc cttcttccgg cggaaaggta gctgaggggg 83820

cgccggcggg gagtcaggcc gggcctcagg ggcggcggtg gggcaggtgg gcctgcgagg 83880

gctttcccca aggcggcagc aaggccttca gcgagcctcg acctcggcgc agatgccccc 83940

tgagtgcctt gctctgctcc gggactcttc tgggagggag aaggtggcct tcttgcgcga 84000

ggtcagagga gtattgtcgc gctggttcag aagcgattgc taaagcccat agaagttcct 84060

gcctgtttgg ttaagaacag ttcttaggtg ggggttagtt tttttgtgtt tctttgagga 84120

ccgtggatca agatcaagga aatctcttta gaaccttatt atggaagtct gaagtttcca 84180

aatgttgagg gttttatgtc taaaagcaac acgtgaaaaa attgttttct tcacccagtg 84240

ctgtcttcca atttcctctt tggggggagg ggtagttact gctgttacta aaataaaatt 84300

acttattgct aaagttcccc aacaggaaga ccactacttt tgatgacttt ggcaagtttg 84360

ctaactactg gaaccctaac ttacaaacga actacttaca tttttgattt ccagttgtat 84420

tacctgccca atgtttacgt agaaacagct taattttgat tctgggtaac gttgttgcac 84480

ttcattaaaa atacatatcc gaagtgagca agtatgggtc tgtggacagc agtgattttt 84540

cctgtcaatt cctgttgctt cagataaaat gtaccagaca gaggccgggc gcggtggctc 84600

acgcctgtaa tcccagcact ttgggaggct tggcgggtgg atcacctgag atcgggagtt 84660

caagaccagc ctgaccaaca tggagaaacc ccgtgtctac taaaaataca aaattagcca 84720

gggtggtggc gcatgcctgt aatgccagct acttgggagg ctgaagcagg agaatcgctt 84780

gaacctggga ggcggaggtt gcggtgagcc gagatagcac cattgcactc cagcctgggc 84840

aaaaagagcg aaactccgtc tcaaaaaaaa agtaccagac agaaatgggt tttgttttct 84900

ttttttgttt tgagacggag tttcgctctt gttgcccagg ctcgagtgca atggcgcgat 84960

ctcagtctcg gctcactgca acctctgtct cccaggttta atcgattctc ctgcctcagc 85020

ctcccaagta gctgggatta cccatgcccc accatgcccg gctaattttt gtatttttag 85080

tagaaacggg gcttcaccat gttaggctgg tcttgaaccc ctgacctcaa gtgggcctcc 85140

cacctcggcc tcccaaagtg ccaggattac aggcatgagc caccgcggcc agccagaaat 85200

gggttttgga aaaagcacta aacaaaatcg aacttggttt catatgacag ctctgctgct 85260

aactgtaaca ggggcagacc agttaaccta cttttctgtc ttctgtcagc tgagaattag 85320

atgattccca aaggcccatt gaactctgaa tgactttaaa tacttcttct taagtgggta 85380

cacggttttg gtaactgatg ccaggtgatg aatgcatgaa agtgcttaat gaatgaaacc 85440

ggtaaaatag taggaggaag ctttattggt aaggcagggg tatacctaat agctctctaa 85500

tttattggta ttgaagtggt taacttttgt ttttttaagg ggggaaaaca ttctaagaat 85560

aatgaggcaa actgcatatt gcacaagaga ctgttgtctc tattcaacaa ataccttttg 85620

agtgtccaga gtctgccagg tgctgtgcta ggccctcacg attgagtagt gaaccagaga 85680

atgtccctgc acccatggag cttattgtct actggggtag acagataata aataagcaaa 85740

caaatcttct ctcttctccc tttcgctcca tgtaagtgtg tgtgtatagg tgtatactta 85800

caagttgagt aaagtgttat gaaagattaa gaggagaaat gcattttggt tagatgttag 85860

aggactcagc aggtgacctt gaaacttaga gctgaaggat cagtaggagg taactagaga 85920

ggccagggaa tcgcatgttc aaaggccagg aggcaagaaa gagcatggtg cccttcaaga 85980

gaggaaagaa ggctactgtg actggagcat agatgtaggc aagtgttggg tgattgagag 86040

ctctacgggc catggttagg ttttattcct aatgccgaga tgccaaacat ggtggttcat 86100

atctgtaatc ccagtatttt aggaggccga ggcaggaata tagcttgaac ccaggagttc 86160

aagaccagcc tgagcaacat gagacctgta caaaacattt aaaaaattgc tgggtatgat 86220

ggtgcacacc tgtggtccca gctactcagg aggctgaggc agaaggatca cttgagccta 86280

ggaggtggag gctacaatga gccatatttg agtcactaca ctccagcctg gatgacaaag 86340

tgagaccatg tgtcaaacaa aatacagaaa gaatattaat ttaaaatttt gaaagaggag 86400

tgatctgaac ttatatctta aaaagatcat tctagggcat ggtggctcat gcctgtaatc 86460

aagggctttg ggaggctgag acaggaggat cacctgaggc cagttcgaga tcaacctgta 86520

cagcatagag agactccatc tctacaaaaa gaaaaaataa atagctgggt gttgtgagtt 86580

attcaggagg ctgaagcaga aagatcactt gagcccagga gtttgaggct gcagtaagct 86640

atgatcccac cactgcaaca cagtgagatc ttgtctcaaa aaaaaaaaaa aatcattcta 86700

ggtgcttttt ggaggctgga tgtggtaaga gtagaagctg gagatggtcc tgttagggat 86760

tcgattcaga ctttaaatac catcaatgca ttgagtccca aatttacatc actacgttgg 86820

atccttgccc ctgaatccag actggtatat ccaactttag gttcagtttg tatctctacc 86880

tgaccaatat agaggtgtcc agtcttttgg cttccctagg ccacattgga agaagaattg 86940

tcttgagcca cacatagagt acactaacgc taacaatagc agatgagcta aaaaaaaatc 87000

gcaaaactta taatgtttta agaaagttta cgaatttgtg ttgggcacat tcagagccat 87060

cctgggccgc gggatggaca agcttaatcc agtagatacc ttcaacttac aatatctaaa 87120

attttatgcc agatttagtc attttaaacc tgctcatcag tttttctcaa gaagtagtat 87180

tttggctttt tttcttttct tttttttgag atggagtttc gctcttatcg ttcaagctgg 87240

agtgcagtgg cggatcttgg ctcactgcaa cctccgcctc ctgggttcaa gtgattctcc 87300

tgcctcagcc tcgcaagtag ctggaattac aggcatgcgc caccatgacc agctaatttt 87360

tggagacagg gtttcaccat gttggtcagg ctggttttgt actcctgacc tcaggtgatc 87420

tgcctgcctc ggcctcccaa aggctgggat tacaggcatg agccaccgct cccggctgca 87480

tttttggatt tttagttgct cagcccaaaa ctttagtaca tctttgaacc tcttctttcc 87540

tcctactcta tatctgatcc atcagcaaat ctgttaggtc tacctcacac atatcgaaat 87600

cctaccacgt ctcaccatct gtgacaatta acaccctggt ctaggcagtc atctctgtta 87660

agattgagtg gttaaggatg tcctctaagg agatgacatt caaatcttag cttaaatgtc 87720

aagagggagc tggttttata aagattgagg aggcagcatt attttgccat aggcttccat 87780

ttggtttcca ttccattctt gatacttatg gtatatattc aaaacaaatg cacagaaaca 87840

gacccaggta tattgggaat ttcggatata gagttcctag ttgggaaaag atagactgat 87900

ctgtaaatga tgctagttat ccatcatctg gcaaaaaata atttcctgcc tcctctcata 87960

tatctcagat caacagactt tttctgttaa gggccaaatc ataaatattt taggctttcc 88020

agaccatatg gtttctgtca cactctcctt tatccttgaa gccatagaca atatgtaaac 88080

aaatgggcat ggctgtgcta cgataaaact ttacttacaa aaactggtag tgggccagtt 88140

taggcatggc cagcactttg ggaggctaag gcagatggat cacttggggt caggagtttg 88200

agaccagcct ggccaacatg gtgaaaccct gtctctacta aaaatacaaa aaatagctgg 88260

gcatggtggt gggtgtctat aattccagct actctggagg ctaagacaca agaatcactt 88320

gaacccagga ggcagaggtt gcagtgagct gagatagcac cactgcactc cagccagggt 88380

gacggagtct taaagcaaaa caaaacaaaa ggtagtgggt tgtatttggc ccatgggctg 88440

tagtttgcca atccctgatg cagaaacaaa ttccaggtaa ataagagcct ggaatgttaa 88500

aaaaacaaaa cttgaagtca tgtagaagaa caggtagggg gaacaatcct gatctcagga 88560

taggaaggga tattgcttaa aataagacac aggaaaatat aatccatgtt gtgtaaattt 88620

gactacgtta aaacttaaaa ctttcgccaa gcgcggtggc tcacgcctgt aataccagta 88680

ctttgggagg ccgaggtgag cagatcacca ggtcaggaga ttgagaccat cctggctaac 88740

acggtgaaac cccgtctcta ctaaaaatac aaaacattag ccgggcgtgg tggcgggcgc 88800

ctgtagtccc agctacttgg gaggctgagg caggagaatg gcctgaaccc gggaggcgaa 88860

gcttgcagtg agctgagatc gcgccactgc actccagcct gggcgacaga gtgagattcc 88920

gtctcaaaaa aacaaaacaa aacaaagcaa aaaacctaaa actttcatac aataaagtat 88980

acctaagata cttctagaag agaagattta catccaggac gtgtatggaa tttctgcaag 89040

taataagtaa aagacaaggg acatgaagag gcagttcaca aaagaggaag ccaaaatgac 89100

caataaacat gaaaggatgt ttaacctcaa aggaaacaag gaaatgaatt aaaaacatca 89160

aatgccattt caaaactagt aagttggcaa aattaaaaat accaaggatg agaatatgaa 89220

gcatggctat atgagtgcat ggaatggtac agtcactttc attaaaaatg cacataattt 89280

gttttttatt tatttttttg agacagtcta tgtcgcccag gctagaatgc agtggcatga 89340

tctcggctca ccacaatctc tgcctcctgg gttcaagcaa ttctcctgcc tcagcctcct 89400

gagtagctgg gattacaggc acatgccaca acgcccggtt aagttttgta tttttagtag 89460

agacagggtt ttgccatgtt ggccaggctg gtctcgaact cctgacctca ggtgagctgc 89520

ttcccaaagt gctgggatta gaggcgtgag ccaatgctcc tggctgaaaa aaatgcacat 89580

aatttgttac ctagcaattc catgtctaga ggcttatcct agagaaattc ttgcttatat 89640

gcataggaag acgtgtacta gaatgttcac tagttgaatg tttaagtgaa aattaggaaa 89700

taaagtaaat gttcattaac aggaaaatga gtaaaggtat atttataaaa caattaagta 89760

gctaaaatga ataaactaga gctgcgtgaa tgaactagaa ctggttcaat agtcatgtca 89820

gattattgaa tgaatacagg tcagatatgt atagagtgtc atttgtgtaa ttaatttttt 89880

tttttttttt gagatggagt ctcactctgt tgcccaggct ggagtgcagt ggcgtgatct 89940

cagctcactg caacctccac ctcctgggtt aaagtgattc tcctgcctca gcctcccgag 90000

tagttgggat tacaggcatg caccaccatg cccagctcat tttcctattt ttagtggcca 90060

cagggtttca ccatgttggc caggctggtc ttgaactcct gacctcaagt gttccaccca 90120

acttggcctc ccaaagtgct aggattacag gcgtgagcca ccgtgctcag ccatttgcgt 90180

gatttttaaa gatgtgcaga ataatgccat taaaaaaaat acacatacat gtatatatat 90240

acacgtttgg ctgggtgtgg tggctcacac ctgtaatccc agcactttgg gaggctgagg 90300

caggaggatc acttgagccc aggtgtacaa gactagcctg ggcgagatag caagacccca 90360

tctcaacaac agaaaggata attaggtatg gtggcatgag aggatcactt gagcccagga 90420

gttcgagtgt tatcaggcca ctgcactcta gcctggacaa caaagcaaga ccgtgtctca 90480

aaaaaataaa aataaaaagt atttgtatgt ggtcatagtc aaaaaacgta catggaagga 90540

aaatgtcttt atttatttat ttattttttt ttttttaaga cagagtcttg ctctgtcacc 90600

caggctgggg tacagtggtg taatctcagc tcaccgcaat ctcggcctcc cgggttcaag 90660

cgattcttct gcctcagcct tctaagtagc tgggactaca ggtacccgcc accacaccct 90720

gctaattctt gtgttttcag tagagacagg gtttcaccat gttggcaagg ctggtctcga 90780

actcctgacc ttaagtgagc cacccgcctt ggcctcccaa agtcctggga ttacaggtgt 90840

gagccactgc gcttggccag gaaatatcta atttagtaag tatttatatc tgggaaagga 90900

agggtcaggt ggtgattcat aggaactcta aagtctatgt ataatactta gggggacaga 90960

aggaaataaa gcaaaatgct gatatttgat tgttgagttg tgtatatgtt agaagtataa 91020

cataggagat ctgattgata gtaggagaat gtttttaggt ggtaaaagtg gaaccgtggt 91080

ggtttgtttt ggcagtagaa tcagttggtc atagtttgta tgtggaaggt aataaacaga 91140

ccatgttaag gatgacttcc ggaattttgg tctgagtagt gggtggatga cagtgtcatt 91200

catgagggaa gatgaagact gaggtaggaa caggtttggg agaagatgac atgttccctt 91260

ttagacaagt ggaattatgg aagatggcag gtaggtggtt agctatatga atttgagata 91320

aaagatttag gatggagata taaatttagg agtaacagcg tatctatggt attgtaagcc 91380

ttaagaatgg gtaggatcag ccaggaaata cagatgtata tgcagaagag aggagtcaag 91440

gaagccaaga caagttaatg tttaaagtga gtgatgtagt ccatgggcag atgctgctga 91500

gagggctgca aacaccagtg accctacaac atttttaaat gtcgtcttcc tgacagcagt 91560

gatcagtacc tgcaacgatc ttatttattt ttttcatgtt agtctccaca cacttgaatg 91620

tagacttttt gaaggcaaaa tcattgcctt ttctgagctg ggagcatgtc tggcacatac 91680

caagcactca acagttgatg tattgacttc atccagatac tctgagggcg agttatttcc 91740

tgctactagc ctttcacctt tcaatgttta agagcacaaa tacagagatg ggcacgtttt 91800

ggcatttctt attttgataa ccttttcctg gtaagatttt ttaatgttga aaaaaaaaaa 91860

caagaaaaga gggttaaaaa tagtcttatg tcagatcctg tgatagaatt cacacttggc 91920

ttaagctgct gggcaccttc ctatcttgga tgtcatatta gcttatctac agcagaattt 91980

ttactgtttt atgtagtaag gaagcaatta tatgattatt ttacagacaa attattcttt 92040

atcttttatt tttttagacg gagtctctct ttgtctccca ggctggagta cagtgtcgcg 92100

atctcggctc actgcaacct ccgcctcctg ggttcaagca attctctgcc tcagcctccc 92160

aagtagctgg gcttacaggt gtccgccacc acacccagct cattgttttg tatttttagt 92220

agagatgggg tttcaccatg ttggccaggc tggtcttgag ctactgacct caggtgatcc 92280

acccgccttg gcatcccaaa gtgctggaat tacaggcgtg agccaccgtg cctggcccag 92340

acaaattatt atactctgag tgttagaggc ttaggatgtt ttcacttgat gctatgggag 92400

gaataagtaa taagatatga tacacaacca aagacctttc ttcactatgc ttctagtagc 92460

tagtactatg gatgacacat ggtaataata ttggttagca tttgtcctca atttactgtg 92520

ctagttactc ttctaagccc cttacaggta tatatttttt ttcatcaata atcctctaag 92580

gtagttttta ttattgacct aattttataa atcaagaaaa ttaagaccca gagaagtaag 92640

taacttgtcc aagatcacat ggcttataag tggtagagcc agaatttgac cccagatgtt 92700

gtgactacat tgtctctcca taagcaggtt caactctttt gactggatgc tgttccaagg 92760

tcacttcctt agagaagcct ttgctgacaa ctaccctcct gtgccctcct ccaaggctgt 92820

ccattgttct agaactttga atactcatct tagaataaag ctggtctaat ttttacagtg 92880

ttatagaatg gatctctgac tgcaaaagtt ggtcataatt atctttttat gttctagtga 92940

aaggcaaaga acaagagaag acctcagatg tgaagtccat taaaggtaag ttctgccctt 93000

ggcagtccac tgcattaaaa agtgatgtgc tttgcatttg tgagttcttt aatcctgtta 93060

tactctctct tttggcatta atcatttctg ccttatttta taattactta tgattttgat 93120

ttatttccct ctttaacctg tataatgctt taacatctag catataataa gtaggctttt 93180

tttttttttt tttttttgga gacggagtct tgctctgtta cccaggctgg agtgcagtgg 93240

cgcgatcttg gctcactgca agctctgtct cccgggttca caccattctc ctgcctcagc 93300

ctccccagca gctgggacta caggtgcacg gcgccacgcc tggctaattt tttgtatttt 93360

ttagtagaga cagagtttca ccatgttagc cagtatggtc tcgatctcct gaccttgtga 93420

tccgcccgcc tcggcctccc aaagtgctgg gattacaagc gtgagccacc gcacccggcc 93480

gtaagtaggc tttttttacc ttaattttat ttttttgaga tggagtcttg ctcttatccc 93540

caggctggag tgcagtggtg ccatctcggc tcactgcagc atccacctcc cgggttcaag 93600

cgattctcct gcctcagcct cccgagtagc tgggattaca ggtggccgcc accatgccca 93660

gctaattttt gtatttttag tagagacagg gtttcaccgt gttggccagg ccagtctcaa 93720

actcctgacc tcaagtgatc cactcgcctt ggcctcccaa agtcctggga ttacaggcgt 93780

gagccaccat gcctggccat aagtaggctt ttactgagcc ttgtgtgtat tggctatcct 93840

agtgattaca gtgaaccagt gcccttctta ttaatcacac atttaattgt tccctaaaag 93900

tgattagttc actttattta tttagtaaga caaaaaatga agaatactct taactgagca 93960

gtctgttaac tgtaggaaag cactgacact tataaggctt agttttctgt catttatcca 94020

gaagtatggt tgattacagt ttttactttt ttatttgaat gaacaacctt aatttaaaat 94080

atattttgtt tattttttgt tgggatcgat acattgtcct tgtttataga ttagagcatg 94140

ctttttaaag atgctgtatt actcactgat tttatttgtc cagtgtacag agattgaagt 94200

gggaaaatta taatggaaat tgtttccata gtcattacat attaatttca tcaatttatt 94260

tccataaaat ctgtagattg ctacttattt agatttttcc ttcaaatgtt tttatgttgt 94320

attgcttgca ctgagtattt attctatatg ctcaatttgc tggagaagaa gactaattat 94380

aacttaggca agttgtaaaa ttagggaaaa aagtaaggta ccttacagcc tagtttactt 94440

atttcttatg taaagccagt tagattccac attagttcaa actgccttct ttgagcaaaa 94500

cttgattggc agtgataaag gcttaaagcc cttctcaagc agagacctgt aaagactaga 94560

tctgactgta gtagaaggaa ggaacttaga tgtttcaggc agtgagaaca ccagtcttcc 94620

actctaaact ttgccactaa cagtatgacc ttgggaagtt gtaactttct tcagattctt 94680

catttgttga atggggggat tggcctagct aatttctaaa tctctactgg gctaaaaaat 94740

tctgtgctta tactctgatt atgaagtaca taatctgtgc ttaacattca ctgacttatc 94800

cttaggataa tacagaagca gtacaagaaa cagcccctca agatgtttgc agtctggtta 94860

gaaagacaaa cttatacaca gaacagtagc aaatagacca aaataataat agctgccatt 94920

tatagaacac ttcttctgtt ctgggcatta gacaaaaact gactataacg gtgaacaaaa 94980

aagacttagg tcctgccctc attgaactta cagattagta ggggagagga acattaatca 95040

agtaattcca cagatggctt agcctagatt ggtagtgatg gaagtaaaga gatgtgaacg 95100

gacttgaaaa aaaattcgga ggcaaaatgg atagaagttt attattgatt aaatatgagg 95160

tgtgagagag agggatattt aagattgata cctaccttct ggcttgccta acagaaccaa 95220

aacaggaaat tatatgttca gttttgttat gttgggtggg aggtgctttt gagtcattca 95280

tttatatatg ttatatatgt tattttatat gcatagtaat tttaaggtct gagttttaaa 95340

ccaaaggtta gagagtgatt ttttagagtc tagcaaacct aagttgaaat cctgcctgtt 95400

gaaatggctg tttactagct cattaaccta gggcaaagta ttcaacttgt tttcattttt 95460

gtcttcatct ctaaaatgag gaaaatatgg tcttacaaga ttgtcctgag agatagatga 95520

aataatatcc aaaaaaaaaa aaggtacata gagaaactcg tatagtgcct ggtatatagt 95580

aggtcctcca ttggtagcta tcattatcta gttttaacat agccttcagt ttgttgaatt 95640

agtcaaactg agtgaagcac tgcaaggaat tcagaggaat ttgagatcaa caaatgattt 95700

ctgaagttta gggaagactt catggcaatg acacttacct tgtataaaag ttgaagaata 95760

agaaagattt gaatgagaga ttctttctct tctccctacc agcccagctt cttatttgag 95820

gatatattgg gcaaaggggc cttcagacaa gtagagggag atttttacag aaagattgag 95880

atgaaggtat agaaggctgt aaagaccaga aaagagaatt gagacagagg aagcaggaag 95940

ccactgtagg tttttgagca agatattgat gctgtaagta tggtgtttat gaaaggttag 96000

tctggaagag atttgcagga tggagacccc ggaagttttt ttgttataat acagaaagac 96060

ttgcactgag ggtgaggtgt taaaaataaa caggtaagta aatgtttaaa catcttgaag 96120

gaaaagtcaa caaatcttgg caagtaaaca gataacagtg aaaaagaatg ggaccaagat 96180

tttgagtttt ggagactggt ggattgaaca gacagggaaa ttgagaggag aatcagatga 96240

tgatgtttta agttgatatt tagacagatt gtgcttgaga tggtaaagtc aatgtgggtg 96300

ggaatgctta gtagcgagta atcagtgata caagaccaaa gcccaggtca aagacaagtc 96360

acagatacag atcagggctt tttcatctgc tccacagagg tgtaccctag gagctgttgc 96420

aaacagtcca tgtggagggt gtgagtaaga tgtttccctt gaatttgcca gaattacttt 96480

tttgttgttg ttgttgtttt ttctgagaca gattctcgct ctgttgccca ggctggaggg 96540

cagtggcgag atcgcgcagc tcactgcaac ctctgcctct cgggttcgag tgattctcct 96600

gcctcagcct cccaagtagc tgggattaca ggcttgtgcc accaagccca gctaatttct 96660

tttgtatttt tagtagagat ggggtttcac catgttggcc agactggtct cgaactcctg 96720

gcctcgtgat ctgcctgcct cagcctccaa aagttctggg attacaggcg tgaaccactg 96780

cacccggtcc cttgttaagt ttattttggt gggaagcaaa ggaggtttca gcttttaaaa 96840

agtttgaaaa ttattgctct ggtaataatt aaagatttga gagtaaatat gctttctagc 96900

agaaagaata aaagaagaac agatagcctc aagaagggga gccaaagaag caggctatat 96960

ctgacacact gggtgttgat aaatgggtat taaaagaatg agagcaatga gcagatagaa 97020

gaggaaatta ggagagtata ataccatgga gaccaagaaa gatagactat caggaaggag 97080

tggtaaaaat aagttactag ttctaagaga gatgttaaga gggaccgggg aaagccttgt 97140

acaaatgagt tagtagcatt ttacattata tacatctaat taagaaacaa tgcgagagtc 97200

tcaccattcc tatagactct tacttgtact tgtctgaaca cgaaaactgg cttttgttta 97260

taaataagct aaaaattatt ttgctccaat ttctcatgaa aataaaaata aaccttcttt 97320

taacattgaa aaaatagttt gaagacagtc actcttcatt ttgtaattcc cacaactatt 97380

attgaatgac tgaaattatc tttattctga agccaaaggg gtgatactga tatttcttca 97440

gactactaaa aatatatttt atgaattttt agtgtgcttt atcttttttt gttttttttt 97500

ttgagatgga gtttcactcc cgttgctcag gctggagggc agtggtgcaa tctcagctca 97560

ctgcaacctt cgcctcccag attcaagcaa ttctcctgcc tcggtctccc aagtagctgg 97620

gattacaggc acctgccccc acacccagct aattttttgt atttttagta gagacagggt 97680

ttcaccatgt tggtcaggct ggtcttgaac tcctgacctc aggtgatcca cccaccttgg 97740

cctcccaaag tactgcgatt gcaggcatga gccaccatgc ctggcctgag gaatattttt 97800

ctaggttccc cccaccccaa gcatttattc tgcaatttta gttttgttcc taaagcaagc 97860

aaggtttaag gatttaaaaa taatccgtat tttagaatgc tttctggctt tgttactttt 97920

tatccacagt agaagttctc agagaatgat ctccctcttt taatttaact ttttggcaca 97980

gtattttgag aattataaat aatattagaa tgttttctgg ctgggtgtgg tggctcatgc 98040

ctgtaatcct ggctacttgg gaggctgagg caggagaatc acttgaacat gggaggcaga 98100

ggttgcagtg agccgaggtc atgccactgc actccagcct gggtgacaga gcaagactct 98160

gtctgggaaa aaaaaaaaaa aaaaaaagag tgttttcttt cctattttcc accacttgat 98220

taagttactt ttcctcttaa gtattttttg ctgagtatgc tgacttaaga gtaatgttac 98280

aaaatttaat ttttaaagtt ctctgaaagc ccctttatga gagttttagg ctatcaaatt 98340

gtgtttaatt cttaacaatt ttttgaaaaa ttatagcttc aatatccgta cattccccac 98400

aaaaaagcac taaaaatcat gccttgctgg aggctgcagg accaagtcat gttgcaatca 98460

atgccatttc tgccaacatg gactcctttt caagtagcag gacagccaca cttaagaagc 98520

agccaagcca catggaggcc gctcattttg gtgacctggg taagtaacta tcatttttta 98580

ttaacttgta ttagaaggat ttgagtacaa tatgtgaaac ttctgtcata ggatacagaa 98640

ctatataatt ggaaagtgct ttggaaaaaa tgtatttaaa ataacagcta caagtataat 98700

gggtagctgt gttgtgttcc tgtaaatata gaatataaag catgcccagt agaaaaacaa 98760

gcatttccag aagaaatata tctgatcact aaatataaat atatgaaaaa gatgtctcac 98820

tttattactg agggaagtgc aaattaaaat aatcagttaa tgttctccta acacattagc 98880

atatttttta aagtttgaca atttgaatgt cagtgaagat gcagggaaat acccctccta 98940

tttagtgata atataatctg gtgaagactc tttggaaagc aatttggaaa tcagtataaa 99000

atatgcatgt catttaggcc actctttcta agacctagcc ctcagatatg ctcattcata 99060

tgtgcaggtg tgtatgtgtg tgtgtgtgtg tgtgtgtgtg tgtatatgta tgtatgtatg 99120

tatgtatgta tgtatgttga aggctattca ttatagtatt gtttgtgata gcaaaaaatt 99180

atggacaaca tataaatatc tgttataggg aaataaccaa attgtggtat acgcatgctc 99240

tggagtataa tatagccatt tgtttctatt tatttatttt cttgagacag ggttttactc 99300

tgttgcccag gctggagtgc agtggtatga tcatggttca ctgcagcctt cacctcctgg 99360

gcacaagcca ttctctcgcc tcagcctcca gagttactag gactgcaggc atgtgtcacc 99420

acacccagat aattttttaa ttttttgtag agacagggtc tcactatgtt gcctaagctg 99480

gtctcaaact cctggcctca agcaattctc ccacacaggc ctcccaaagt gctgggatta 99540

ccaacgtgaa ccaccacacc tggttcagtg tagccattta gaaatctaaa aaagacgtgg 99600

gaaaatgtct aaggcatgtt taaatgtgag aaaagcaagt cacagtatgc atggtaaaat 99660

ccgttatatt aaaataagtt cttccaaaac aaaaacatat gcaggagacc tttattttgt 99720

cagtatttct tacccaaatt tctgcactta gaaaattgca tgtcatgttg tcataagttg 99780

aaaaaaagat ccatgaacca atggacttct aataaaatca gtcctgcttt tgacatctct 99840

ctctactttt gtgtatattc aaaccagagt gtcaatgtgt ttgtggggca cacttagcaa 99900

taatacatag cagacaaaat gcatatagct cagagagtaa aattgtaagt tttgctagat 99960

cactcataaa ttgctgatga gaatttaaaa tggtgcagat gctctggaaa acaggcagtt 100020

tctttctttc tttttttttt tctttttgag acagggtctc actctgttgc gcaggctgga 100080

gtacagtggc gtgattacaa ctcactgcag cctcaccctc ctcaggttca ggtgatcctc 100140

cctcagtctc ctgagtagct gggactatag gcatgcacca ccacgcctgg ctaatttttg 100200

tatttttttt tttttttttt gtagagacgg ggtttcgcca tgtttcccag gctggtctca 100260

aactcctgga atcaagcgat ccacttgcgt aggcctccca aagtgctggg attacgggcg 100320

tgagctactg tgcctggcct aggcagtttg tttgtttgtt tgtttgtttg tttatttatt 100380

tgtagacgga gtctcacagg ctggagtgca gtggcccaat ttttggctca ctgcaacctc 100440

cgcctcccag gttcaagcta ttctcctgcc tcagcctcct gagtagctgg gatgacaggt 100500

gcctgccata atgcctggct gatttttgta tatttagtag atatggggtt tcaccatgtt 100560

ggtcaggctg gttttgaact cctgacctca ggtgatcagc ccgcctcggc ctcccaaagt 100620

gctgggatta caggcatgag ccgtcatccc tggctggtgg tttcttatga cgtgaaacat 100680

gcaattacca tatgacctag cagttgcact ctgtatttat cccagataaa tgaaaactta 100740

ccttccaata aaaacctgtg cacaaatgtt catagcagct taatattgaa aaactggatg 100800

ttcttcagca ggtgaatgaa ctggttcatt cataccatgg aataccattc agcaataaaa 100860

aggaacaaac tgttgataca tttaaccacc tggatgaata tcaagggaat tatgctgtca 100920

gacaaaaacc agtccctaaa gactacatat agtatgattc cgtttggata atattcttga 100980

aatagagaaa ttaagagaaa tgaaaagatt agtgtttgcc agatgttaga gacagggagg 101040

tgagaggggt aagtgggtgt agttataaaa gtgcaacatg agggatcttt gtgatgttga 101100

agttgtatct tggcagtgga tgcagaaatc tcaatgtgat aaaattacaa agaactaaaa 101160

acaagaatga gtatagataa aactggggaa atctgaacaa gttagagtgt tgtatcactg 101220

tcagtatctt agagtgatat tgtactatag ctttgcaaga tgttaccatg ggagaaacta 101280

aagtgtacaa gggatctcta ggtattatta tttttttaga gatggggttt cactatgttc 101340

cccaggccgg tcttgaactc ctgggctcta gtgatccgcc tgccccagcc tcctaaagta 101400

ctggaattac aggcgtgagc gaccatgcct ggccctttca gtattgtatc ttagaacttc 101460

atgtgaatct agcattatct catagaattt aattaaaaga aattgtaaac ctcacagaag 101520

atcagaattt cctcaagttt gtgatgttga caaagatgaa ctagttgaca ctgacagtaa 101580

gactgaggat gaagacacga cgtgcttcaa aaaaatgatt tgaatatcaa tggattaaga 101640

agaactcttt tgacaaattg atgaaaccct cagtcagttt tataagaatg cccatcttta 101700

tgatcatgct atgaaagcca atttttaaaa aaattttttg tctttcctaa caattagctt 101760

gtggttataa tttaaattta gttaaatata agataaatga ttttttatta agtttagttt 101820

catttttcaa ggtacgatct caaagctact ctttaaccta ctatgaatga ataatgctga 101880

gttcataaca tctttgtaga tatatccaca attttccctc aggataagtg cctacaagtg 101940

gaattactgg actgaaaata atgcagtttg ctaagacttt gctatctgtt cctgaatgct 102000

cctccaaaaa ggttttgcca gtttacatcc tcatgaccag cgaatgagag tgttgcctat 102060

tttcctgtgc ccttgttact gcttaataat ttttgaaaaa aatctaattt gacagacaaa 102120

aatgcatttt atgttaattt gcttttctgg gatttttaat gaggttgagt atagttttta 102180

atatttttat tggccccttt ggaactagta tcataagttt tttttcttaa gaatttatgt 102240

agtctgggct gggcgcagtg gctcacgcct gcaatcccag cactttggga ggccgaggtg 102300

ggtggattgc cgaaggtcag gagtttgaga ccatcctgac caacatggtg aaaccgaatc 102360

tctactaaaa gtacaaaaac tagctcagcg tggtggcggg tgcctgtaat cccagctact 102420

taggaggctg agtcaagaga atcgcttgaa cccgggaggt ggaggttggt tgcattgagc 102480

cgagatcgcg ccattgctct ccagcctagg caacaagagt gaaaagtctc aaaaaaaaaa 102540

aaaaaaaaaa aaaaaagaat ttacatggtc tgaattgcca ttaaaagaga tatgagaatt 102600

attgagtaac aaataacttt ttaataattt aggcaagttt tggacgattg tactttgttt 102660

agaaaccaaa agcatagtat ttgtagtttt tttatttact ttagttgcta ggaagtaaac 102720

tttattcaag gtctctggta ccagttgttg ctaaaagtga ttgactaatc tgtcaatctg 102780

aaattatttg ttgctgaact gctaattctt ttgcttctat cttttaggca gatcttgtct 102840

ggactaccag actcaagaga ccaaatcaag cctttctaag acccttgaac aagtcttgca 102900

cgacactatt gtcctccctt acttcattca attcatggaa cttcggcgaa tggagcattt 102960

ggtgaaattt tggttagagg ctgaaagttt tcattcaaca acttggtcgc gaataagagc 103020

acacagtcta aacacagtga agcagagctc actggctgag cctgtctctc catctaaaaa 103080

gcatgaaact acagcgtctt ttttaactga ttctcttgat aagagattgg aggattctgg 103140

ctcagcacag ttgtttatga ctcattcaga aggaattgac ctgaataata gaactaacag 103200

cactcagaat cacttgctgc tttcccagga atgtgacagt gcccattctc tccgtcttga 103260

aatggccaga gcaggaactc accaagtttc catggaaacc caagaatctt cctctacact 103320

tacagtagcc agtagaaata gtcccgcttc tccactaaaa gaattgtcag gaaaactaat 103380

gaaaagtgag tatgtgattt tcttgtgtgt acatatgtgt ctcactttct ttttttaatt 103440

tactaagcag aacttcagat gaggaataaa atgattggaa tatttttttt ctcctctaac 103500

tacttgtaaa tttgggagaa tttggagagt gtagtagagt cagatcagtg tatggaaaag 103560

gagcaggagt gactggacct tctaagaagt gtgttatcag aattagtaaa tgaagggtca 103620

aatgtcctac ttttcccctc cactgatttt gacatcaaac cattatccac atagccttat 103680

ttcctccctc ggtcttaatt ttattaatat tttactgcac tttgcagata aaatttttaa 103740

aaaattttta aaaattgcca ataagtgaca tttattaagt tcagtgctta gtgtatattt 103800

ggattttatt tattagtcac aagacctttg tgcaggtagt aggcatgatt atcttttttt 103860

ttttgagatg gagtcttgct ctgtcgccca ggctggagtg caatggcgcg gtctcggctc 103920

actgcaacct ccgggttcat gccattctcc tgcctcagcc tcccaaatag ctgggactac 103980

aggcgcctgc caccacaccc ggctaatttt tttgtatttt tagtagagac ggggtttcac 104040

catgttcgcc aggatggtct cgatctcctg actttgtgat ccgcctgcct cggcctccca 104100

aagtgctggg attacaggca tgagccaccg cgcccggact gattatctta tttacacatg 104160

agaaaaccag ggcttagaaa ggttaggtaa cttcctctag gttgtacagt aaatgtggac 104220

ctagaagcat tttgacaaga gcacctgttt ttttttcttc tctattagtt tagaaattat 104280

atactcttaa ttatcacctg ggattttgat tagacagcct tcatgttctt tttcatctta 104340

aatgttcttt gtgtcttaaa gggctaagtg atttcttcag atcttttagt tcactcattc 104400

tcagtgaact aaaatgaggt ctaatctgct actgaatcaa gttttcagca tgttatttcc 104460

ttcctccctc cctccctcct tccttccctc aaccaggctc ccgaggagct gggattacag 104520

gcgcccgcca ccactcctgg ctaattttta tattttagta gagacggggt ttcaccatgt 104580

tggtcaggct gatcttgaac tcctgacctc aagtgaccca cctgcctcgg cctcccaaag 104640

tgctgggatt acaggcatga atcaccacac ctgacggcat gttattttca tcgcaaagtt 104700

actgtaagct gggagaagtg gcacacactt gtactcccag ctactcagga agcttaaggt 104760

gagaagattg cttgagccca ggagttttga gaccaacctg ggcaacacag caagacccca 104820

gctcaaacaa agaaaaaaag ttattgaatt ttttatttct atggatcatt ttttgtagtt 104880

tcttattcct ttcacccttc attcccactt ttgatcccat cttttattta tttagtttta 104940

ttaaatgtat atttgtctga taattctgct atctacagtt ttttgtggac ctgactcagc 105000

atttctttgt ttcttcggat tcagactgtt ggtggcttgt gattttagtg atttttggcc 105060

gtgaacatgt ttcttggact tttgtctgtg ggaattctct gtgtactctg tataaattaa 105120

gttacttcag gtgttttgca ttttcttttg ccatgcacct ggggcctggg tcactaccct 105180

tctggtacca cttaaaactg aatttttgtc ttgggtgctc gtactgatcc tgtatgagta 105240

caggtttata cttactgtag aaatatggtg tttgattatg gggtattgtc ccagatggtg 105300

ctggagtatt aatatgctct ctgttaaact taatgtgttg tccctgtaaa actccaaaat 105360

tctgaattcc agaatactac tggccccaaa tgtttaagat aagggcactg cctgtatttg 105420

tttctgcctc ccactatttt ccttagttta acacaaactc acctttttaa aaaacatttt 105480

gagagaattc agtattggga agagtttcta acctgtttct ggaaatggaa gtccaaagtc 105540

tgtttctgta attgtttttt ttttgagatg gagtctcact ctgtcaccca ggctggagtg 105600

caatgacgta ctctcagctc actgcaacct ccacctcccg ggttcaagcg attctcttgc 105660

ctcagccccc tgagtagctg ggattacagg tgcccaccac catgcctggc tgatttttgt 105720

atttttagaa gagatggggt ttcgccatgt tggccaggct ggtcttgaac tcctgacttt 105780

gtgatctgcc cacctcagcc tcccaaagtg ctaggattat gtttctgtaa ttgtaataca 105840

tttattgttt ttagaaactg tctttgcttt agtggtaatt ttcaataaaa atagaaatag 105900

cagtggagtt attaaaagag cattagttac atttttccct ttttcattat cttcaaatat 105960

tatatatagt aagtttgacc tttttaaaat gtatacttgt atcagtttta acacatacat 106020

agattcctgt aactgtcacc actataaggg taaagaacag ttagttcctt cacctttgaa 106080

gtcaagcccc acctctatcc caacacttgg caaccgctga tctttctccg tctcaatagc 106140

tttgcctttt ctcttttttt ttcttatttt tttttttgag acagcgtctt gctctgtcgc 106200

ccgagctgga gtgcagtgag gcaatctcgg ctcactgcaa cctccgcctc ctgggttcaa 106260

gcagttctcc tgccttagcc tccctagtag ctgggattat aggcacgcac caccacaccc 106320

ggctgatttt tttgtatttt tagtagaaat ggggtttcac catgttggcc aggctggtct 106380

caaactcttg acctcaagtg atccacctgc ctcggcctcc caaagtgctg ggattacagg 106440

cgtgagccac tgtgcccaat caggactttt tttttttaaa tttacattca acttgtcatt 106500

tttttcttgt atggattgtg ccttcagagt cacacctaag agccctttgc ctaagcaaag 106560

gtcatgaaga ttttctcata tgtttccttt taaaagtatt gtggttggcc aggtgccatg 106620

gcttatgcct gtaatctcag cactttgaga agctgaggtg ggcagattac gaggtcagga 106680

gatcgagacc atcctggcta atgcggtgaa accccatctc tactaaaaat acaaaaaaaa 106740

aaaaaaatta gccgggcgtg gtggcgggca cctgtagtcc cagctacttg agaggttgag 106800

gcaggagaat agtgtgaacc cgggaggtgg agcttgcagt gagccgagat cgcgccactg 106860

cactccagcc tgggcaacac agtgagactc catctcaaaa aaaaaaaaaa agtattatgg 106920

ttttacactt tacgtttaga tatatatctt ttttgagtta atgtcgtata agtatgaggg 106980

ttacgtcaga ttttttgttt tttgtttatt tttacatatg gatgtctagt tgttctaata 107040

ccatttgttg aaaagacaac ctttactcca ttgaattgcc tttgtacttt tgccatattt 107100

gtctaggcct gtttttggac tcctttttct gtttcatgat gtgtgtgtct attcctttgt 107160

taataccaca tggtcttaat tactgtatag taagtcttaa aattgggtaa tgctggcctt 107220

ataaaacgaa ttgggaagtt tttattttta ctcttatttc cattttctag aagagattgt 107280

gtagaattgg tgtcatttct tctttagata tttggttgaa ttgggaagtg atgccatctg 107340

ggcctagggt tttgtttttt gtgtgtgaga cagagtctca cttctgtcac ccaggttgga 107400

gtgcagtggt gagatcttgg cttactgcaa cctctgcctc ccaggttcaa gttatcctcc 107460

tgcctcagcc tcccaaatag ctgggattac aagcgtgtgc caccatgccc gactaatttt 107520

tgtattttta atgcagacag ggtttcacca tgttagccaa gctggtctcg aacttgtgac 107580

ctcaagtgat tagcccacct tggcctccca aagtgttagg attatagatg tgagccaccg 107640

tgcctggcag gggcctaggg ttttcttttt cagagtattt taaactatga attcagatta 107700

tttaatagat ataggactat ttaagttatc tgtttcttct tgagtgaatt tttactgtag 107760

tttatggcct ttgagtaatt aattgtattg aattgtcaaa tttatgagcg tgtaattatt 107820

tatagcattt cgggtttgta gtggtatccc tcttttattc ctggtgttgg caattgtgtc 107880

ttgtttttct ttgtcagatt gtatagggat ttattagtct tttcaaagaa ctagcttttg 107940

ttttgatttt tctgttgttt tgttttcaat tttattgatt ttctgctctt tattatttct 108000

tttctattat ttctgcttgc tttgggttta ttttactctt ttttttttct ccaagttgct 108060

taaagtagaa acttagattt ctggtttgag acctttcttt tctaagataa gcatttaata 108120

ctgtaaattt ccttctaacc actgctttag ttacaccccc acaaattctg gtattttgaa 108180

ctgagcacaa atgaaatgtt ctaatttccc ttgaatctta ttcttttacc aatgaattat 108240

ttagaaatat gttatttagt ttgcaagcaa ttggagactt ttttcctgtt atttttctac 108300

catttatttc tcatttcatt atattatggt cagagaatat attttgaatg atttcattta 108360

ttaattttta aaaataacat taaaaaattt tttaaaatgt gaatatacca catacagtat 108420

aaagattgta cattctgttt ttggacagtt ttctataaat gtcaagttga tttagttggt 108480

taatgatggt gttcagtttt tctttattct tgctgatact ttgtatgcag ttatatcact 108540

ttattactca gaagagtgtt gaactttcca actacaattt ttttttccaa ttttactttc 108600

agctctatct ggttttgctt catgtatttt gaggctctgt tgttaggtgt gtacacattc 108660

aggatgatat cttctgggtg aattgcctgt tttatcatta tgtaattccc tctttatggt 108720

aattttcctt gttctaagat cagaaatatc tgttgtccaa tttatataga cactgcagct 108780

ttcatttgat tagtgcttgc atggcatatc tttttccatt tttttacttt tgatctacct 108840

ttataattct atttaaaggg ggcttcttgt aggcagcata tagttgggta gtgttattta 108900

tttatttatt tatttattta tttatttatt tattgagaca gagttttgct cttgttgccc 108960

aagctggagt gcagtggtgc aatcctggct taccacaacc tccacctcct gggttgcagt 109020

gattctcctg cctcagcctc ccaagtagct gggattacag gcacgcgcac catgcctggc 109080

tgattttttg tatttttagt agaaacggat tttcaccatg ttagccaggc tcgtcttgaa 109140

ctcctgacct caggtgatcc acctgctttg gcctcccaaa gtgctgggat tacaggcgtg 109200

agccactgca cccggctgag tcatgttatt tttaatcttt tctcacaata cagggttttt 109260

gttggtaaat ttaattattt taatataaat tttagtataa ttatttacat taaatgtaac 109320

tgttgcactg gggtatttat aatgtgtaaa tataattatt ggtattaata taattatatt 109380

actcataata atattaatat ctttggattt agattaccag tttagtatat gtttttctgt 109440

ttctccctct ttgatttccc cttttttgct tttttttttt ttttaattct tatttttttt 109500

tagtatttgt tgatcattct tgggtgtttc ttggagaggg ggatttggca gggtcatagg 109560

acaatagttg agggaaggtc agcagataaa catgtgaaca aggtctctgg ttttcctaga 109620

cagaggaccc tgcggccttc tgcagtgttt gtgtccctgg gtacttgaga ttagggagtg 109680

gtgatgactc ttaacgagca tgctgccttc aagcatctgt ttaacaaagc acatcttgca 109740

ccacccttaa tccatttaac cctgagtggt aatagcacat gtttcagaga gcagggggtt 109800

gggggtaagg ttatagatta acagcatccc aaggcagaag aatttttctt agtacagaac 109860

aaaatggagt ctcccatgtc tacttctttc tacacagaca cagtaacaat ctgatctctc 109920

tttcttttcc ccacatttcc cccttttcta ttcgacaaaa ctgccatcgt catcatggcc 109980

cgttctcaat gagctgttgg gtacacctcc cagacggggt ggcagctggg cagaggggct 110040

cctcacttcc cagatggggc agccgggcag aggcgccccc cacctcccag acggggcagt 110100

ggccgggcgg aggcgccccc cacctccctc ccggatgggg cggctggccg ggcgggggct 110160

gaccccccac ctccctcccg gacggggcgg ctggccgggc gggggctgac cccccacctc 110220

cctcccagat ggggcggctg gccgggcggg ggctgccccc cacctccctc ccggacgggg 110280

cggctgccgg gctgaggggc tcctcacttc gcagaccggg cggctgccgg gcggaggggc 110340

tcctcacttc tcagacgggg cggccgggca gagacgctcc tcacctccca gatggggtgg 110400

cggtcgggca gagacactcc tcagttccca gacggggtcg cggccgggca gaggcgctcc 110460

tcccatccca gacggggcgg cggggcagag gtggtcccca catctcagac gatgggctgc 110520

cgggcagaga cactcctcac ttcctagacg ggatggcagc cgggaagagg tgctcctcac 110580

ttcccagacg gggcggccgg tcagaggggc tcctcacatc ccagacgatg ggcggctagg 110640

cagagacgct cctcacttcc cggacggggt ggcggccggg cagaggctgc aatctcggca 110700

ctttgggagg ccaaggcagg cggctgggaa gtggaggttg tagggagctg agatcacgcc 110760

actgcactcc agcctgggca acattgagca ttgagtgagc gagactccgt ctgcaatcct 110820

ggcacctcgg gaggccgagg caggcagatc actcgcggtc aggagctgga gaccagcccg 110880

gccaacacag cgaaaccccg tctccaccaa aaaatgcaaa aaccagtcag gtgtggcggc 110940

gtgcgcctgc aatcccaggc actctgcagg ctgaggcagg agaatcaggc agggaggttg 111000

cagtgagccg agatggcggc agtacagtcc agcctcggct ttcacaactt tggtggcatc 111060

agagggagac cggggagagg gagagggaga cgagggagag cccctttttt gctttctttt 111120

ggattatttg aatttttcct taaatttatt tatcttactt atttatttat ttttttgagt 111180

gattctcctg ccacagctcc caagtagctg ggactgcagg catgtgccac tacacccagc 111240

taattttttt gtatttttag tagagacagg gtttcaccat attggccagg ctggtcttga 111300

actcttgacc tcaagtgatc cacctgcctc ggcctcccaa agtgctggga ttacaggcgt 111360

gagccaccat gccctgcctt tttctagaat ttatatattg agttcttgat tgtatctttt 111420

tatgtaggct ttttagtggc ttctctagga attacaatat acatactttt cacagtgtac 111480

tcacatttaa tattttgtaa cttcaagtgg aatgtagaaa acttaaccac cataaaaata 111540

gaactaggga tgaggttaaa aaagagagag aaaagaaatg taataaagat ttaataacac 111600

cgtttttttt tttttttctc tttttttttt gagacagagt ctctctttct gttaccaggc 111660

tggagtgcag tggcgtgatc ttggctcact gcaacctccg cctcctgggt tcaagtgttt 111720

ctcctgcctc agcctactga gtagctggga ttacaggtgc gcgccaccat gcccagctaa 111780

tttttgtatt tttagtagag acggtttcac tgtgttggcc aggatggtct cgatttcttg 111840

accttgtgat tcgctctcct cagcctccca aagtgctggg attacaggcg tgagccaccg 111900

cgcccggcta agtctttaaa tatttttttg acattgcact ttttctcttt tccttctagg 111960

attttagtaa cccaaatgtt agttttgtta ttgtttggca ggttcctgag gctttcctta 112020

cttctttaaa tttttttttc ctgttgttca gcttcgaaaa tttctattca tctgtcttca 112080

aattcactgg ttctttcccg ttatttccat tctgttattg agtctttgta gtgaatttta 112140

aattttgttt attatgtttt ttagttctaa aattttcttt ttttgtgtat gtcttatact 112200

ttgctcctga aactcttatt tgtttcagga gtgatcttat ttcttagagc atggttttag 112260

tagctactta aaatttgttt tatcatccca gcatatgtgt cctcttgatt gtcttttctc 112320

ttgtgagata atgggatttt ctggttcttt atatgacaat taattttgga ttgtatcttg 112380

gacagtttga cttacgttac atgattctga atcttgttta aatcctgtgg aaaatattga 112440

agtttttgct ttaacaagca gttgacctag ttaggttcag tccacaaatt ctaagcagca 112500

ttctgtcggc tctggttcca tcatcagttc agttttgtat cttatctgct tatgtgcctt 112560

tctgtgtcca gtctgggacc tggccaatgg tcaggtccca aagcctttgt acacttttag 112620

aagcagggcc atgcacaccc agctcacgag tggccccggg agtgcacata caactcgacg 112680

ttttcatggg ctccttcttt tctgtgatgt ccctgacacg ttctgccttc taagaacctc 112740

cctttatccc tttcctgttg tctggctaga aagtcagggc tttagattcc ctatacttca 112800

gcacacttcc tgtagctatg tcaacctctg tggccacgac ttcttcttct tgggactgca 112860

gtttctcttg tcagaaagta ggattcttgg agctgctgtc attgctgctg tggctgctct 112920

gatgctgcct gggagtcgaa ggagagaaag gaacaaaaca aaacaaccca ggggatttcc 112980

tccactctct ttgatccgtg agagccccct ttcctgttcc tcagaccaga aatagagggc 113040

ctgtcttgga acttcttctt tgtgcatctg gtgtgcagtt tcagcttttg agtccaggcc 113100

aggaggtgct ggacaaactt gtcaggagta cggaggtact gcaagttctg attacttttc 113160

tcagtccacc tgcttccaag tccttggatg catttgtcca ttgttttgag ttgcattcca 113220

tgggagagac agaagagtgt gcttatttca tcttgacata cttattagga tttcatatca 113280

aatcaacgga tgatattctc tatattaatt tgctgttttc cctttagcaa gcacattagg 113340

aaaataacac tttaacaccc gcctttggtg gtttctgtca taattattaa tacttgactt 113400

tttttttttt tttgagacgg agtctcactc tgtcctttga ggcattgtcc ccataaactt 113460

ttggtaaagc atcaataatt ttatctttca tccacacaag cttcaccata aatttgatgt 113520

ttattcttcc attttagcag aattcatgtt gctccaatag gggctgtctt caaactgatg 113580

ttttctcctt cttagtgcct cagagtagat cctgttcaga tacgttataa caggttaata 113640

tgagtttatt ttggtgtaaa agtactttga aattcatgca tagttttttc atcatatgca 113700

ttttccatag ctttgaacac ccccatgtaa ctctcctctt ccacaaacca aacaatgaaa 113760

aagcaccttt gtgatggaag tttattttgc aataggaact cacagtgatc taagccctgc 113820

tattcatgaa tataattcat tactggagtc caagttgctt tttggttttt gaagttctct 113880

tcttcccttg caggtataga acaagatgca gtgaatactt ttaccaaata tatatctcca 113940

gatgctgcta aaccaatacc aattacagaa gcaatgagaa atgacatcat aggtaagcag 114000

tgcttgaaac tatggcaaaa aaaaaatgac aaaaaatgca cagaactgac aattttcgtt 114060

attgactaag ataatttttt cttaacatgg aatttagcag ttcccttcct aatttgtttt 114120

ctgagtattt tttatatcgg attatagctc actttaaaag tttctcggct gcattcggtg 114180

cgagggtctt tgcctgggcc agatgggctg cagtgtagcg ggtgctcagg cctgcccgct 114240

gctgagcagc cgggccggcg ggcggctacg ctaaccggca cagaccaccg gatggactgg 114300

ccggcagccc cgcaccagtg cacgaagtgg gcgggacaga aacttctggg gttggaagtc 114360

cagtgaggct aaaagccggt accaaagtct ctaggcatca gggctgcagc ccaagagtct 114420

cacgaccagt gggcaactgg atggccagac aggtgtctca gtggtggcct ctccgtctca 114480

gggcttcatc ccacttctca gtgggcctga cgtccctggg caccctggat gtctacctgc 114540

attagccaga gccatcacat ggcctgtgac ttgccttttt ttgccagttg attgtgccac 114600

acacagtgtc atttctgtgt catttggcac agctggaggt gcaaggagga gggcagcctc 114660

atgtccagtc ccagtttcac gtaactttat tcttctgaat aaagacaatt tgctaacctt 114720

aaaaaaaaaa aaaaaaaaaa agtttttctt atatgttgga cccaaattct taggctttaa 114780

cctgaataac aatgacagca agatcaataa atagtacaca tttattaaac actcactgtg 114840

tcccagacaa tattccaagc actttttatg gatagactca ttttaacttc taaagaactt 114900

tgtgggataa atacagttat tttatagatg aagaaactga agcacagaga agttaagtgc 114960

tttgtccagg gtaacagctc agatatggca gagtcaggat ttgaaactag accctcacat 115020

accttaactg ctgtgctgtg gcagtgtttt tcatactgta ggttgggacc agccttctct 115080

tatgccctca ccccctgcca aaaaaaaaaa aaaaaaaaaa aaatatatat atatatatat 115140

atatatatat atatatatat aatatatata tatataaaat atatatatat ataaaatata 115200

tgtattagta tatatgcata tatagtatat attatatatt agtatatata ctaatatata 115260

atatacatat tagtgtgtgt atatatatat atactagaat aaaaaaatca aagtatctca 115320

gagtagtaag gacaaacatt tcagaaaaat gttttcatta tatatacatg tatgtatgtg 115380

tatgctgatt caacaaatat atttcttata ggttatagca aaatagtttg aaagctttta 115440

ctgtgtttta tcaggaagac cttaggtgaa cgtatattca cagataaaag aggttattta 115500

ttcattcaat aaatattaca ttctcataag tcctaatatt atgtattttt attcttcaaa 115560

aaagttagta tttgtgattt atgaaataag acatgttctt gcacttttag cagatctgtc 115620

ccgatgttgg gcttctttaa tccttagtgt gggtgctttg cactcactca ctgctgggga 115680

cagcaagacc cctgttagtc tcagctgtgt ttcttaaatt ggcccactgt accttccagt 115740

tagctattct ggggtccatg tcatgttggc tccattttcc ttttctttct cccacacaga 115800

tacctataac ggctataaca taggcctggt ggctgttggt ggcttatccc tatctgcttg 115860

tatttaaggg gtactgtttc actgagtttt gctgacagat gttgtcatga gatttgaggt 115920

tttctgtgtt gttgctctat ttttatgtgg gaatttgcta ctatcatcat ccctagacca 115980

gcttttccta gtaatacaac agggatgttc tgactgatta gagtttgcct gtttgaagaa 116040

ttggttggct agtgattttt ttttgagggg agtctgtacc agttaatagc ctgactggcg 116100

tgtggataaa aaggaagcag tttcaagtca aataaaacac ttaaaatgaa accacactgc 116160

aactctcttt cttttactta agcttaatca aattaatgat gatgtaatcc catgaaggaa 116220

aagtcttctg aaggatcaag ttgataacat tttgtgatca aagaatttga gaaaacctct 116280

atcccagtgt ctatcattat atattttagg atgttaatta cctgtgtggc tttaggcaag 116340

tcatttttcc tccttgagcc ccattcttaa tcctgtccaa attatttgtc tcctcttgca 116400

gttggactat tttaatatag ctgtccttca agtgagtttt gttcaaagga gccttcactt 116460

tagctcttac tgtgtaccca ctttgcatag tcttgtttta aatgtaatcc ttggattttt 116520

ggtgttgcta actaattact gtttttatgt gaggatttag agtgatccag aatctatact 116580

tgcactacct ccttcatctt ccacaaatgt ttgaagtggt agaattttta aaaactttga 116640

aggtacagct gacagaattt gctgatggtt tggaagtgag tggtatgaga gggaaaaaaa 116700

ggaataaagc atgactgcat tttttgtttg tttgtttgtt tgtttttgag acggagtctc 116760

actctcgcca ggctggagtg cagtggcgtg atcttggctc acggcaacct ccgcctcctg 116820

ggttcaagcg attcccctgc ctcagcctcc caagtagctg ggactacagg cgctcgccac 116880

cacgcctggc taattttttt ttttgtattt tagtagaaac ggggtttcac cgtgttggcc 116940

aggatggtct ccatctcctg acctcatgat ctactcacct tggcctccca aagtgctgag 117000

gttacaggca tatatataag catataaagt gtgttatagc atacaaacag gtatatatat 117060

aaacatgcag tccacacagc tgataggaat gaggcagtag tgaaggagaa gttgatgtag 117120

gagaggggac agttgttaca ggaaagaagt ctggaggcag aagggatgaa ttccagtgct 117180

cacatagaag attgcttaga tgggagcaag gacaatttat ctagagtcac aggaaagaat 117240

gcagtacacg ggtagagatg caggtgagtt gaaagatgtg agagatgatg gaaataattt 117300

tctgattgct tctatattct caaggaagca ggaagcaaag tcctcagcaa agagaataga 117360

agaggtgtta aatatttgag aaaggagatg tactgtagaa aaaaaaaaaa ctcagtttct 117420

ccttctgaac tctcacaaaa cagaaccctt ccatgactct agttgtgtgg ggttttttcc 117480

ctgtcagcta ccaattctgc agatgattgt tcagtgaaca ccaactgggt gtcctctaag 117540

tcagttcagt tctcacactg tttacctgga gatagcatca gatcccacag attgaggact 117600

ctgtcccaca agactgcctc cacttcagat gccagtctca agtacaagtt gtggcctgtg 117660

cttctgactg accttctata aattggagtt cccacagtcc cctccttggg ttcaataaat 117720

ttgctagagc agctctcaga actcagggaa atgctttaca tatatttacc catttattat 117780

aaaggatatt acaaaggata cagattgaac aggcagatgg aagagatgca tgggcaaggt 117840

atgggagagg ggcacagagc ttccatgcac tctccaggtc atgccaccct ccaagaacct 117900

ctacagattt agctattcag aagcccccct ccccattctg tccttttggg ttttttgtgg 117960

agacttcatt atataggcat gattgatcat tggctattgg tgatcagctc aaccttcagc 118020

cccctcatcc cgggaggttg gtgggtaggg ctgaaagtcc caaacgtgta attctgcctt 118080

ggtctttctg gtgattagcc ctcatcctaa agctctttag aggccacagc cacaagtcat 118140

ctcattagcc ttcaaaagaa tccagagatt ccatgaattt taggcgctgt atgctaagaa 118200

actggctaaa ggccagttgc aatgtctcag gcctgtaatc ccagcacttt gggaggctga 118260

ggcaggagga tcgtttcagg ccatgagatc aaaaccagcc tggtcaacat agtgagaccc 118320

ccttacaaaa aatttaaaaa ttggccaggc gtaatagctc ttgtctgtag tctcagctac 118380

tcagaaggct gaggatcact gagccctgga gttgaaggca gcagtgagcc atgatcgtgc 118440

cactgactcc ggcttgggtg acaaagtgag accttgtctc agaagaaaaa ggaaaaaaaa 118500

aaaactgggc aaagactaaa taacatattt cacagtatca cagatttgta ttgtctagga 118560

aagtgaatgt aaacagacca ggacactagt atgatccctt ggtttcatga aggtcccact 118620

aaagtcatga acacaaagtg agactaggca tcatgttata tggtttttcc agccatgttt 118680

aacagctagc taaatagcta attgtttcgc tgcagtttat tttagcagtt ccttatttta 118740

gcacatttca tgttttaaaa tttctaccaa taacatttta ataaactttt ttacagataa 118800

cttcacaaat ccataatttt ttaagttaca atcccagaaa tagaattgct cattgaaagg 118860

gtatgttcat ttttaaagtt atgctagaaa ctgccaaatt gccttcagaa aaaggtgttt 118920

gtatccccac taacactagt gttagttttc ttgtgccctt gctcaagtat acatattatt 118980

aaaaacaatg ttgggccagt ttactagata aaaggtgtag tgcctcctta ttctaatcta 119040

tttgattact agtgagtatg tatgtctttt cacgttggtc attttatgtt tgttcctttg 119100

tggattgtca tgtcctttgc tcatttttct tttggaacat ttcttagtag tttataagag 119160

ctcttggtat tttaatgata gtaacctttt aactgtcatg catgctgcaa atcttttttc 119220

tgtttgtttg cctttgtatt ttgtttttgg agggtttcta tgtataggaa ttaaatttta 119280

tgttgttaaa tcttttgatt tctgcttttg catatgtact tcaaaagact ttctatttta 119340

agatcaagtg ttacctgtat tttcttttag ttctatttaa aacctcttaa tttatatgcc 119400

tgtgctgtta actcccaagt tgattcacaa gtgtgtatac atagtttgaa tttagtggca 119460

atttaattat ttacaacttc ttttgcagca aggatttgtg gagaagatgg acaggtggat 119520

cccaactgtt tcgttttggc acagtccata gtctttagtg caatggagca agagtaagtt 119580

agttcatatt ttcacattgt gcatcctagg gaatttgggt tcattgttag gaatgggctt 119640

cactcagcta aaaacaaagt atttttgaga atttaaatat tttggatatt tacaagatca 119700

tataaagcat actctatctt ggttaacagt ttcttttaaa tataaattat gtgaactctt 119760

aaaattttca ttttcatttt caatgttaat atttcctaag ttaaaataat ttgtttttag 119820

ttctgaaata atttggggag tgattgagtc tgtagtgatt atgactatta gaattggttt 119880

atttatttaa ataatgcatg tcttcagatg gctctcctaa tttgttagtt aggctttaag 119940

ctaaatggat gctatataac taaatccaca tagatttgtt gaaatggctc cagaggtttt 120000

ttagatttat tactgctatg tgcccttaaa aaaaatctat tcattctttc acttaacatt 120060

tatcagaaga gtgctctgtg taagacgtgg ttaggcatag tgccagtctt gaaggaagtt 120120

acagcctaat aaaagacata gggcatgttg tttggttact gtaatatgaa gtggcatgtg 120180

ttaaatgtca ggggagaact acaaagtcat aaaaaggtgg gagagattac atacaggtaa 120240

aggaatcagg aatgacacca tggggagtaa ggtagtgttg acctaggcct ttaagataca 120300

atagggacag tatggaaaga gtatattttt cccacttaaa ctctttcctt ggtcgttccc 120360

tcaaattttc ccttttgtcc atgtgcaggc actttagtga gtttctgcga agtcaccatt 120420

tctgtaaata ccagattgaa gtgctgacca gtggaactgt ttacctggct gacattctct 120480

tctgtgagtc agccctcttt tatttctctg aggtaaagtc tgcatttctt ttcacactct 120540

attcgagcat tccagcctct aactatcaat gctggggccc tgtctatagg aaataacaca 120600

gaagagccaa gtcatttcca aaaagatgta tcattgtttc aagttgtttc tgatggcaag 120660

agtaatttaa taatatatta gagagaacat gaaaattcaa tgtattaaat aactctaatt 120720

ttgagaaacc taattaaact actgcatgta agagagtgca tgtttttaat tatttggagc 120780

tattttaaaa ccacagaatt tgaaacttgc ttccagtgca taaattgcag accagacttc 120840

agaagagaaa aaaagtagta aattttttct tatgctcatc atttttactt tagtcacttg 120900

ataggattgc ccagtgaaga agcatttgca acagacaatg agtatattaa tctttttgag 120960

gcatacagtt tagtataatg ctctttgtta ggcttcaaca agtgaaatta ttttgttgga 121020

aagcaaatga ctattaagta gaaagaggat tcccagtctc acaaagcagt aatttagaca 121080

ctcgattctg cctctttaca agaatacagg tactcagttg atttgttttc tcactccctt 121140

tctttgctat aagtttaaat caacaatttg tttaggttaa tatgtcctca tggaatggtg 121200

gaaatgatca gatataaaat atttggtttg gttagtttac tctttatatg tttgctggca 121260

aggaaccaca aatccagttt agtataattt ttactctagt tcactaaaag tttgcatcca 121320

gctgtgtagg tagtgtttgt ttcttgttaa cttttttttc gtctaaaaga atactttaaa 121380

acttttcaat ctcaaatgac tgtaacttgc tgacaggtgt taacagaaga agtagatctt 121440

tttgtttttt gcttatgacc tgtattttaa tatttgagct tatagattag agattgtgag 121500

agaaatctgt ttatagtctt attttccctt gtgtattttt tcttcctagt acatggaaaa 121560

agaggatgca gtgaatatct tacaattctg gttggcagca gataacttcc agtctcagct 121620

tgctgccaaa aagggccaat atgatggaca ggaggcacag aatgatgcca tgattttata 121680

tgacaagtga gttatattga tagatggatt cagcagatac ttattgaaca tttgatatgt 121740

tttgtggaaa taaagatgaa taaactcagt ctctgttgtc aaggagctca caggaggcag 121800

cataaaagct gcttttatat ggtgtttgta aagctttggg ggttcttaga acaaaagttt 121860

ctgctgggaa aggggaggtg tatgtggggt aaacaggatg gcaatggtgg tgttcaagga 121920

gtgtttccca gaagagagat tttgtttgga tcccaaagaa agaagggaat tttgctaccc 121980

agagaaggca gaaaacaaca ttctaggcaa aggcattggc ccagaagcca tggaaacgta 122040

ggggaaagtg gcactttcaa gaaacttgag tttagataat caaaggagtg gggaataaat 122100

atgaggatgc tggtactaat tggaatagat tgtaagggac cttgaatgcc tatttatggg 122160

tatattatac tttctgtata aatctgctca ggcacgttgt taattagttt tttattagtt 122220

ttcactgaaa atgagaggat ggaaacatca tacagtaaac aaaattgaaa atatctggtc 122280

aggcagatga tgagcttgtg gccagctctg taacgtatgg tattcttttc atttaacttt 122340

tcttactctg taaaaaaagt aattcgtggt cgggcacggt ggctcactcc tgtaatcaca 122400

acactttgag aggcagaggc aggtgaatcg cttgagccca ggaatttgag accagcctgg 122460

gcaacatggc aaaacccgcc tttactaaaa atacaaaaat tagctgagcg tgatggcgtg 122520

cgcctgttgt cctagctact taggggcctg aggcagaagg atcacctgag ccttgggagg 122580

tcgaggctgc agtgagctgt gatccactgt actccaccct gggcagggca gtagagtgag 122640

accctgtctc caaaaaaaaa aaaaacaaca aaggtaattt gttatttgta tccttaagca 122700

aatgctaaag gggtaacttg gggatagaga aaagtccaca gatgttaggg tttgaagaca 122760

ctaatagtat ctaggccagt ggttcctgaa cattagtctg tgggctcttg ctgggctgtc 122820

tgcataggaa tcacctgaga gcttattaaa aataggtttt caggctggtt gcggtggctc 122880

acgcctataa tcccagcact ttgggaggct gaggcaggcg gattacttga ggtcaggcgt 122940

tcaagaccag cctggccaac atggtaaaac cccgtctcta ctaaaaatac aagaattagc 123000

caggcatgat ggcacacacc tgtaatccca gctactcagg aggctgagga aggagaattg 123060

ctcgagcccg ggaggtggag gttgcagtga gcggagatca tgccactgca ctccaggctg 123120

gctgacagag ggagactctg tctcagaaaa aaaaaaaaaa ataggttttc agtctgggta 123180

ccggtggctc acacctgtaa tcccagcact ttgggaggcc aaggcaggca gatcacttga 123240

ggtcaggagt ttgagaactg cctggccaac atagtgaaac cttgtctcta ctagaaacta 123300

caaaaaatta actgggcatt ttgacgggtg cctataatcc cagctactag ggaggctgag 123360

gcaggagaat tgcttgaacc cgggaggcag aggactgcat ctcaaaaaaa aaaaaaaaaa 123420

aaaggtttcc agtccccctg tctcagaaat tctgattctg caggtttgag gtgtgaccag 123480

gaatctttat ttttagaaga cataccagat aattctgata aatagccagt ttagggatgt 123540

agtctaattt tcctattttg caagtaagga aaataaggcc cagagaggta atgattttct 123600

caaagtcaca gaacaagtta gtggcagaat ttggactgga atgcagttct taatgttctg 123660

tccagtgttt attctggtac agtatgtttg tagaaggtat tacgtaagaa acattgttat 123720

atagatgttg agataggaag agtttacatt tagaaatttg gtctaaaatg cctgaacatt 123780

caagtcgtgg aggagtattg accaacttac tcaatacaac ataggagatt cacattttgt 123840

tacaaaaatg ctgatttaaa aggagagttt tctttttttt cttctttttt attttttgag 123900

atggagtctt gctctgtcac ccaggctaga gtgcagtgac acgatctcag ctcactgcaa 123960

cctccacctc ctgggttcaa gcggttctcc tgcctcagcc tcctgagtag ctgggattac 124020

aggtgggggc caccacgccc agctaatttt tgtattttta gtagagacag ggtttcacca 124080

tgttggccag gccggtcttg aactcctgac ctcaagtgat ccacccacca ctgcctccca 124140

aagtgctggg attataggcg tgagccactg tgcccagcct gcttgttttt gtatcatata 124200

tatgcatcat cataatcatg cattatcaac ctttgtattt ctgtcaggac atagaaacca 124260

ttagagtgct tggaagagag cctttttttt tttctcgcat ttaatgcttt ttttggtatt 124320

catttcataa tcagcttacc aaaacattac ctgcattata ccccatcaag gtagaaatct 124380

ttgtgttatc aatattggtt actccctttc cacaccgagt catcagtaag tcctgttcta 124440

tccaaatagg tcatatgcat ctagctcacc cctcagtgct gttttgtttt gaatttgtac 124500

atgtttactc ctgatgcctt gtagttatga tgatgtgttc ttattttatt ctgtgcatac 124560

aagttctcag ctcgcttttt agggaaaatg accatgtctt cctttcctat aaattccttt 124620

ctatctatca agtcctcaac agagaatagg tacccataaa tatgtgattg ttagtttctt 124680

tgcctcagtt gtagtctgat ccttacagct tttaaacaac agtagagttc accgtcaaga 124740

actaaggatg gttggcaggc agatagaaag gtagcaagtt gacccaacta tctctgggga 124800

agtgggaaca aagaaaggtt acatcagcac tgtcatcaca tagctctata gttctaggcc 124860

tgcaggctca atcaagtagc cttgtataag attctctgga ggaggtgctg aaagttgctt 124920

atacttgcta tggaatttga ttttacttcg gatatctttt taccataggt acttctccct 124980

ccaagccaca catcctcttg gatttgatga tgttgtacga ttagaaattg aatccaatat 125040

ctgcagggaa ggtgggccac tccccaactg tttcacaact ccattacgtc aggcctggac 125100

aaccatggag aaggtaaccc agaacttcaa acgtatcaaa ctacaagaag ttttattggt 125160

agaactcata aaatataagg tgggaaaacc aagcagaata gcacagtgga aattgaagca 125220

gtccagcaaa gtgattaaga gcagaggcct tgagtctggc ctggtatgta cagtcacgtg 125280

ccacataaca ttttagtcaa cagtggactg cgtgtacgat ggtcctgtac gattataatg 125340

gatcaaagct ggtagtgcaa taataacaaa agttagaaaa aataaatttt aataagtaaa 125400

aaagaaaaaa gaaaaactaa aaagataaaa gaataaccaa gaacaaaaca aaaaaaatta 125460

taatggagct gaaaaatctc tgttgcctca tatttactgt actatacttt taatcattat 125520

tttagagtgc tccttctact tactaagaaa acagttaact gtaaaacagc ttcagacagg 125580

tccttcagga ggtttccaga aggaggcatt gttatcaaag gagatgacgg ctccatgcgt 125640

gttactgccc ctgaagacct tccagtggga caagatgtgg aggtgaaaga aagtgttatt 125700

gatgatcctg accctgtgta ggcttaggct aatgtgggtg tttgtcttag tttttaacaa 125760

acaaatttaa aaagaaaaaa aaaattaaaa atagaaaaaa gcttataaaa taaggatata 125820

atgaaaatat ttttgtacag ctgtatatgt ttgtgtttta agctgttatg acaacagagt 125880

caaaaagcta aaaaaagtaa aacagttaaa aagttacagt aagctaattt attattaaag 125940

aaaaaaattt taaataaatt tagtgtagcc taagtgtaca gtgtaagtct acagtagtgt 126000

acaataatgt gctaggcctt cacattcact taccactcac tcgctgactc acccagagca 126060

acttccagtc ttgcaagctc cattcatggt aagtgcccta tacagatgta ccatttttta 126120

tcttttatac tgtattttta ctgtgccttt tctgtatttg tgtttaaata cacaaattct 126180

taccattgca atagtggcct acgatattca ttatagtaac atgtgataca ggtttgtagc 126240

ccaaaagcaa taggttgtac catatagcca aggggtgtag taggccatac catctaggtt 126300

tgtataagta cactctgtga tgttagcaca atggcaagca gcctaacgga aattctgttt 126360

attgattgat tgattgattg attgattgag acagagtttc actccattgt ccaggctgga 126420

gtgcagttgc acagtcttgg cacactgcaa cttctgcctc ccaggttcaa ccaattatcc 126480

tgcctcatcc tcccaagtag ctgggattac aggcaggcac caccatacct ggctaatttt 126540

tgtattttag tagagacagg gtttcaccat tttggccagg ctgttctcga actcctgacc 126600

ttaagtgatc tgcctgcttt ggcctccgaa agtgctggga ttacaggcat gagctaccat 126660

gcctgggcag taactgaaat tctctaatgc cattttcctt atctgtaaag tgacgataat 126720

atgcacgttt acctcaaagt tactttgatg attaaagtaa ggtaatgtat ataaaataca 126780

tattaacata gtacctgaca catggtaagc atcaaaaaat gttaactact tttattacta 126840

ttattattac gtatttttaa ataattagag agcagtatca aaaattagct gggcgtagtg 126900

gcatgcacct atagttccag ctactcagga ggctgaagct ggaggattgc atgagcctgg 126960

gaattaaagg ctgcagtgag ccgtgttcat gcccctgcac tccagccttg gtgacagagc 127020

aagaccctgt cttgaacaat taaagaaggc attatgccgc aacgttagct tagaaatgat 127080

ccacatatat caccagtaac tgtcaacagg attggaaccc tagttttggg tattatgatc 127140

acaaggtatt attaatagct tattaataat aaagcgttgg ctaggcacgg cgactcacat 127200

ctgtaatccc agcactttgg gaggccgagg tgggtggatc acctgaggtc aggagtttga 127260

gaccagcctg accaacatgg agaaacccca tctctactaa aaatacaaaa ttagccgggc 127320

gtggtggtgc atgcctgtaa tcccagctac ttaggaggct gaggcaggaa aatctcttga 127380

acccgggagg cagaggttgc agtgagctga gatcgcacca ttgcactcca gcctgggcaa 127440

caagagcaaa actccgtctc aaaaatataa ttataataaa taaataaaag taaagtattg 127500

atgtttgtga atgatttatt cttctaatga actagaggag atttttccag gaatttcaga 127560

gccagtgagg ttatgttgct tgtatgtgtc atgtgtatcc aggtgaaaaa acttaattaa 127620

acgctattat ataataccat acataaaaac tgaattttag gaatactgaa gaatgacata 127680

tagaagtcaa atcattaaat agctagtagt aaacagaata gagtgtcagc tgttacccaa 127740

tgatgataat attttcacga ttaaaattaa accttttctg attttaaagg aaaagttcag 127800

atctgtatca tataaagaat gtaaattttc agggtaataa aattaaaatg cagagagaaa 127860

aatgcaaaaa tagttcttac tagatgtgtg tatgtaagga acttagacta attttaagaa 127920

cactgtcaag accctggtag ttaggtagga aaaaagacat gaatgattca ttcaacaaaa 127980

actttgagta tttctgtgct agatggtagt gttacagtgg taaacaaaat aaatgtgttt 128040

ctgctatcct ggagcttagt ctacaaaaaa ggtacatatt ggccgggcac ggtggctcac 128100

gcctgtaatc ctagcacttt ggaagatcga ggcgggtgga tcacctgagg tcaggagttc 128160

aagaccagct tggccaacat ggcgaaaccc cgtctctact aaaaatacaa aaattaactg 128220

ggtgtggtgg cggacacctg taatcccagc tactcgggag gctgaggcag gagaatcact 128280

tgaacctggg agacagaggt tccagtgagt cgagatcatg ccactgcatt ccagcccggg 128340

ggacaaaagc gaaaatacgt ctcaaaaaaa caaaaacaaa caacaaaggc acgtattaaa 128400

tacgaacata aatatttaca aattatactg aataagttct catgtttatt atttgcttgt 128460

ccagttacaa acttttcctt cgtagaatta gaaatataaa taataaacat gagaactcat 128520

tcagtataat taataattat taaatgtaaa taaaaacatc tatgtacaat taggcattta 128580

tttaagaatt atttgaaaaa aaaacaatgt ggaaacagat attttgatat attgctagtg 128640

attgaaattg ataatgttct tttgaagagt aaagtgacca tatatattaa agttaaaatt 128700

taactcagca atcacacgcc tggtgagtta tcttaaggaa atcagtttga aagtaaaatc 128760

aatatatgca caaagacttt aacatttatc ataaaccaga aaaatcgagt ttcaaattat 128820

atcctatgga ctattttctg ctaaaaagta ttaatatcaa ctttatgtaa tactttcgtg 128880

acaaatattt tgggggagaa aacccaacaa aattacatgc attgtaattt tttttttttt 128940

ttttttttta gacagtcttg ctccagcgtc caggctggag tgcagtggtg caatctcggc 129000

tcactgcaac ctccatctcc caggttcaag caattctcct gcctcaggcc tcccgagtag 129060

ctgggattac aggcgctcac caccatgcct agctaatttt tatagttttt agtagagatg 129120

gggtttcatc atgttggcca ggctggtctt gaactcctgg tctcaagtga tccgtctgcc 129180

tcggcctcct agagtgctga gattacaggt gtaagccact gcacccagcc ttatgcatta 129240

taattttaat ttgtaaactg tacaaaggga taatacttgt agtacaacaa gaagtaaaaa 129300

catttgttat aggtagttaa catttgtaac cagtagaatt ataggtaaaa tttatttatt 129360

taaaacagtt ttagttggat ttgatttcaa ctttaaaata atgcttttca tctctatcag 129420

gtctttttgc ctggcttttt gtccagcaat ctttattata aatatttgaa tgatctcatc 129480

cattcggttc gaggagatga atttctgggc gggaacgtgt cgctgactgc tcctggctct 129540

gttggccctc ctgatgagtc tcacccaggg agttctgaca gctctgcgtc tcaggtattg 129600

actgattgcg tctgccatta gggagaaaag catacacatc ctttccttca catcccagta 129660

acagatccta ttatttgtaa attttaagtt gtggaaaaaa aagataaaag ccaggcacag 129720

tggcctgtgc ctgtaatccc agcactttgg gaggctgcgg tgggcggatc acacgaggtc 129780

aggaattcga gaccagcctg gccgacatgg tgaaacccca tctctactaa aaatacaaaa 129840

attagccggg catggtggca ggcacctgta atcctagcta cttgggaggc tgaggcagga 129900

gaatcgcttg aacccaggag gcagaggttg caatgaacca aaatcacgcc actgcactcc 129960

agcctgggtg acaaagtgag actgtgtctc aaaaaaaaaa aaaaaagaga gaaataaaat 130020

tagcctactt actatcttct aatcaaagca tttgtggtaa cttaaaatat actgtattgt 130080

aaagtatcat gctgtttcat ttaggccatt attctatttg aatctgtggc tgtttctctt 130140

aataaatcaa gtaatatgga atatattcat agcctctgaa gagctcttta tgtaagtatt 130200

tatttaggat actttttgta aaataagtga atgaattctt aggtctcctt tttttttctt 130260

ttcttgagac agggtctcct cgctgcaacc tggaaattct gggctcaaat aatccaccca 130320

ccacagcctc ctgaatagct gggactagag gcatgcacca ccacgcctgg ctaatttgaa 130380

attttttttt ggccaggcat gatggttcac gcctgtaatc ccagcacttt gggagaccga 130440

ggcaggcaga tcacgaggtc gggagatgga gaccagcctg gccaacgtgg tgaaaccccg 130500

tctctactaa aaatacaaaa attagctggt tatggtggct catgcctgta atcccagcta 130560

cttgggaggc tgaggcagga gaatggcttc aaccagggag tcggaggttg cagtgagccg 130620

agatcacgcc actgcactcc tgcatggtga cagagtgaga ctccatctca aaaaaaattt 130680

tttttttaaa tgatggagtc ttgctgtgtt gctcaggctg gtcttgaacc cctgacctca 130740

aatgccgcct gcttcagcct aagtttcttt tttttttgta aagagacagg gtcttgctat 130800

gttggccagg gtagtctcaa actcctggct tcaagcagtc ctcccacctt ggcctctcaa 130860

agtgctggga ttacaggcgt gaaccactac ctataatgtt gtgtttcact caaggccttt 130920

tgatttcgtt ttgcattacc gtgccacatt gtgcatttcc ttgacctttt ttgggttttt 130980

tggagtgctt tcatatgtta aaccatacct gattctcctc aaaatcacac aaagtagaat 131040

atcctaagac aagaaatcta aggaggcata aagaagttaa ctggttttat taaactcaca 131100

cagtaaatga tagagccaga aatattcccc ttctagtgtt cttcaccatc agcttaatgt 131160

agcataataa ttttctaatt actgttgaca aataaataac cctttgaatt ttcaatactg 131220

ggccttggat aaattttcct aatttgtaag agagtattat cgtattgcca tttacaaagc 131280

tctcctgagt atctttttct tctgttaagt ttacctagga gataaactgc tgagtatggt 131340

tgccattttg gttttttgat ataggttaga atgtcttggt tttttttttt tttttttttg 131400

gtttttgttg ttgtcattgt ttgagacagc atcttgctct gtcgcccagg ctggagtgca 131460

atggcacgat cgtggctcac tgcaacctcc acctcccggg ttcaagcaat tctcctgcct 131520

cagcttcctg agtagctggg attacaggca tgtgcaacca cacctggcta atttttgtgt 131580

ttttagtaga gaaggggttt caccatgttg gtcaggctgg tattgaactg ctgacctcat 131640

gatccacctg cctcggcctc ccaaagtgct gggattgcag gcatgagcca ctgcacctgg 131700

ctgaatgtct tgtttttgat taggcactta agaaaggcct aggtactaac cataaaatat 131760

atttttatac cttttgttga tactatatat atagaaaact gcacttatca taaccttaga 131820

caccttgaag aatgttcaca agcagaacta acccatgtga cccagcatcc agatcaaaaa 131880

cagcattatc agcccctcta gaagccctct tgggcccctt ccattcactg tccttcttgt 131940

caccagggta gctactatcc tgacttttga tggcatagat tagcattacc tgttcttgtc 132000

attttataaa taaaaccata ctgtgtattc ttttcttgta cagctttatt gtgctaattc 132060

acatttacat catacaattc agtggttttt atatggtcac agagttaggt aaccattacc 132120

acatcgattt tagaacattt ttttcactcc agatagaaac cccctttact taaactccaa 132180

atcccccact ccaccagccc taggcagcca ctagtctact ttttatctct atagagacaa 132240

tagatttgct tattctggac atttcataaa catggaaccg tatattatgt ggtcttttgt 132300

tgccaactgt ctttcactta gcatcatgtg ttcaaaagag catcatgtta tccatgtttg 132360

gcatgtatca gaattttatt cctcattatg gccaaatatc ccattgcaag gatttatgac 132420

attttatttg aattgtaccc tcctttctgc catttatcaa taatgctact gtgaccattt 132480

gtgtacaagt ttttgtgtgg atacaggttt tctttttgtt tttaaatttg aggtggagtc 132540

ttgctctgtc gcccaggctg gagtgcagtg gcacaatctc ggctcactgc aacctctgtc 132600

tcctgggttc aagcagttct cctgcctcag cctcccgagt atctgggact ataggcacgc 132660

accaccacgc ccagctaatt ttttagtaga gatggggttt caccatgttg gccagtctgg 132720

tctcgaactc ttgacctcaa gtgatccacc catctcggcc tcccaaagtg ctgggattac 132780

aggggtgagc cactatgccc ggctgtggtt ttcatttctt ttgttgtata tacataggag 132840

tagaattgct gagtcaagag gtaactctta aacttattga aaaactgcca gattgttttc 132900

cgaaaaggct gcaccatttt gcaatcccac cagcagtgta tgagttttac agcttctcca 132960

catttcattg gaacttatta tctgtttggc tgtttttaaa aatgatagtc attccaataa 133020

gttctacttc agtgtggttt ttgcacttct ctgatgagta atgatgttga gcatcttttc 133080

atttgcttat tggcctttgt tctagctttg gaaaaatgtt tattcaaatc ctttggccat 133140

ttttattttt atttttattt atttattttt ttttgagacc aagtctcact ctgtcagcca 133200

ggctggagta caatggtgtg gtctcagctc actgcaacct ccgcctcctg tgttcaagtg 133260

attctcctgc ctcagcctcc cgagtagctg ggattacatt tcaggcacct gccagcatgc 133320

cgggctgatt tttgtatttt tactagtgac agggtttcac catgttagcc aggctggtca 133380

caaactcctg acctcaggtg atctgcctgc ctaggcttcc caaagtgctg ggattacagg 133440

cgtgagccat tgggcccagc ctagattttc ttttttcttt ttttttttga gaaggagtct 133500

tgctcttgtt gcccaggctg gagtgcaatg gcacaatctt ggctcactgc aacctctgcc 133560

tcctgggttc aagcgatttt cctgcctcag cctccccagt agctgggatt acaggtgcct 133620

accaccacac ccagctaact tttgtatttt ttttagagac agggtttcac catgttggcc 133680

aggctggtct caactcctga cctcaggtga tccacctgcc ttggcctccc gaagtgctgg 133740

gattaccggc atgagctacc aggcccagcc aattttctca ttatattgcc caggctggtc 133800

tcaaactcct gggttcaagt gatcctcctg ccttggcctc ccaaagtgtg gggagtacag 133860

gcgtgagcca ccttgctcag cccctttgcc catttttaaa ttagattgcc tttttatatt 133920

gagtttcagg agtcctttat atattctaga taaatgtccc ttatcaaatt atattatttc 133980

caggtatttt cttcattctg tgagttgtct ttcctctacc ttttaaaaaa ggtgggtttt 134040

tgtttgtttg tttgtttgtt tttttaagat aaggtctcat tctgctgccc aggctggagt 134100

gcagtggcac aatcacagct cactgccacc tcaacttcct gggccgaagt gatcctctta 134160

cttcagcctc ctgaatagct agggccatag atacacacta tcacacccag cttttttttt 134220

ctgtttgtag agacagatct tactgtgttg cccaagttgg tctcaaactc taggctcaaa 134280

gtgattctcc cacctctgcc tcccagagtg ctgggattac aggtgtgagc cacacgcaac 134340

ctgtcttttc actattaata gtgtcttcct gcttcagcct cccgagtagc tgggattaca 134400

ggcacccacc accatgcctg gctaattttt ttgcattttt agtagagaca gtgtttcacc 134460

atgttcaccc ggctggtctt gaactcctga cctcaggtga ttcacctgcc atggcctccc 134520

aaagtgctgg gattacaggc gtgagccact gcacccggcc aaaatattgc cttcttaaca 134580

gtattgtctt ctaatttgtg aacatggatg tatcttcatg tatttatgtg ttctttcatt 134640

tcagcagaat tttgtagttt tcagagtaga agcctttcac ctccttgggt catttattcc 134700

tatgttttaa gttcttttcg attccattat aaatagaatt gttttcttaa tttcattttc 134760

agattgtttg atgagagagc atagaaatac aagtgatttt tacatgttga tcttgcaact 134820

tcaactttga taaatctgat tgttagctct aatagttttc ttgtggattc tttaggattt 134880

tcaatatata agatcatgtc atttatggat agagatagtt ttttttctgg ctagaactta 134940

cagagcaatg atgagtagaa gtggcagaag caaaaatctt tgtcttgttt cctatctgac 135000

agggaaagct ttcagtttca tcatttaata tgatgttagg tgtgggtttt caataaatgc 135060

cttttttcag attcaggaat ttccctatca ttcctgattt tttaaggctt tttttttttt 135120

ttaaatcatg aaagggtgtt gaatattgtc atgttctttc tgtatcagta taaatgatcc 135180

tatggatttt gggttttatt ctgttgatgt gaaatattaa ttgattttca gatgttaaac 135240

caaccttgca tacctgagat gaatctcact tggtcatggt gtataatctt ttcaatatgc 135300

tgctggattc catttactgg tattttgttg aagattttgt atctgaacgc ttaagataac 135360

atttacactc tatcagaaat gaattgacca taaatgtgag agtgtatttg tgggttcttg 135420

attctcttcc attccaaaga tagacataca tccgtctgta tgtctgtctt tatgccagta 135480

ccatactctc ttgattacta ttgctttgta ataagttttg aaatcagaaa gtataaatga 135540

gattttggta tctgagtaac agtcctcata gaattagttg ggaaatattc cctctttatt 135600

ctggtccctc tttctttttt gtttaactgt gtatcttgga gattgttcct tctcaacaca 135660

tgagagccgc tttccctacc ctcccacccc tgctatagag aggtctataa gtgtctgttc 135720

aattatttta tttacttaac ctattactta gtcggggaca ttaagcttgt ttatgtcttt 135780

tattttaaac aatgctgcag tgaataatct tgtatataag tcattttcca tcaatataag 135840

tctctctgta actgaatttt tagaagtgga atttctaggt caacctatgg ctctgtattt 135900

cacaaaaata ccaattctgg tttttcttgt ggaggtgggg agtaggaggt agaatgctgg 135960

aggagaactt gctgtactca gctggctagt cattttagaa aggtttcctt agcttctttt 136020

tgtcatatgg cctcaccaag aatcaaaaac attcctattt accctgtaaa catggggctt 136080

tactacccaa gatacatatt tctggatgta tgacagcttt tcatattgaa gaaataatgc 136140

tgtgagtaca gcacatttgt tggaacttag gtcgttaaga atgtcttata aattcataca 136200

ttatacattt tattttattt tattttttag tttttgatac agagtcttcc tctgtcgccc 136260

aggccagcgt gcagtggtac aatcttggct cactgcgacc tccatctcct gggctcaagt 136320

gattctcatg tctcagcctc cagagtagct atggttacag gcatgcacca ccatgcccgg 136380

ctaatttttt tatttttagt agaaactggg tttcaccata ttgaccatgc tggcctcgaa 136440

ctcttggcct caagtgatcg gcctgcctca gcctcccaaa gtgctgggat ccttgtattg 136500

ggtaaaagat gaatattgag ggctgcatgg tggctcatac ctgtaatccc agcactttct 136560

gagactgagg tgggaggagt cctggagccc aggagggtga ggctgcagtg agttgtgatc 136620

gcgccattgc acttcaacct aggaattata ggcttcagtc actgtgcccg gcatgtacat 136680

tttaatattg tgctttcctc ttttagctat agtatgaggt tacatttcag agtcattgtt 136740

gttaagcatc ttaatagtga tgaggttgag tgaaagttac ttctatttca aacactgaag 136800

aaaattttgt acaaatctgt cacattccaa gcccaggact gattgtttca tatacttcta 136860

attttacaat ttctattgta gtccagtgtg aaaaaagcca gtattaaaat actgaaaaat 136920

tttgatgaag cgataattgt ggatgcggca agtctggatc cagaatcttt atatcaacgg 136980

acatatgccg ggtaagctta gctcatgcct agaattttta caagtgtaaa taactttgca 137040

tcttttaaat tttttaatta aattttacat ttttttctaa tctattatta tatgcccaga 137100

actttcactt agagtgtgca gtataatgtg gtggttaagt ataaaggctc tggagtgact 137160

tcctgggttt taatcttggc tctgccattt attggcagcc gctaacctct tggtatctca 137220

gtttcttcat ctgtaaaatg agaataataa agtgaaaaga tgccaacatc atttactctg 137280

ggctgcataa ctgatacttg gaaaaagtat tcctttgagt ttaagaatta agttggttat 137340

tcattttagc ttgtaataaa aagatagtga ttcataggat atgccactta ctgaaattta 137400

ccacagatcc aatcataaaa tcactttctc ttccctaaag atagcttgat taacatgtaa 137460

aggtgtgtaa aggcttgatt acactaccct gatccgtacc ccagttccca gcagcaccat 137520

gaaaaaggga tttcaacata tttaattact ttcagtagaa agtaacagtg gtaggccagg 137580

cgcagtggct cacacctgta atcccagcac tttgggaggc cgaggtgggc ggatcacgag 137640

gtcaggagat tgagaccatc ctggctaaca cgatgaaacc ccgtctctac taaaaataca 137700

aaaaattagc cgggcatggt ggcaggcacc tgtagtccca gctacttggg aggctgagac 137760

aggagaatgg cgtgagcccg ggaggcggag cttgcagtga gcttagattg tgccactgca 137820

ctccagcctg cgcagtggag cgagactctt gtctcaaaaa aaaagaaagt aacagtggta 137880

ttgggagact gaggagccta gaaagtactt gaaggaagta aaaggtttgt ttgaccacat 137940

tgtatttgga aagccagctt tttcagctgt gtcagctttg tgtagtgatt tttagttctt 138000

cttttagaaa ataacggaca aggccgggca cggtggctca cgcctgtaat cccaccactt 138060

tgggaggccg agacgggcgg attacctgat ctcaggagtt cgagaccagc ctgggcaaca 138120

tggtgaaacc ccgtctctac taaaatacaa aaagttagcc gggcgtggtg gcgtgtgcct 138180

gtagtcccag ctactccgga ggctgaggca ggagaattgc ttgaacccgg gaggcggagg 138240

ttgcagtgag ccaagatcac accattgcac tgcagcctgc gcgacagagt aagactctgt 138300

ctcaaaaaat aataataaaa taaaaaagaa tggacagtaa acctaaatga gttcattccc 138360

aaagatgatg ttattcttaa gggatggttc atttatttaa gaccttacat aaagtctatc 138420

aattgcgtga tttttcactt ctgtaattgt gtgtatgtat aatgtaaata tatatgtttt 138480

tgttttgttt tggttttttg agacggagtc tcgctctgtt gctcaggctg gaatgcagtg 138540

gtgcaatctc agctctctgc aacctctgtc tcccaggttc aagcgtttct tctgcctcat 138600

cctcccaagt agctgggact acaggcacgt gccaccacgc ccggctaatt ttttgtattt 138660

ttagtagaga tggggtttca ccgtgttagc caggatggtc tcaatctcct gacctcgtga 138720

tccacccgcc ttggcttccc aaagtgttgc tattacaggc atgagccacc acacccagca 138780

tgtatttttt aaatgtataa aatgaagcag aaaagagaaa tgataatttt tcttcatctt 138840

gaaagattat cttcaccagg cgcagtggct cacacttgta atcccagcac tttgggaggc 138900

ctcggcaggc ggctcacttg agttcgaaac cagcctggcc gacatggtga aactccgtct 138960

ctactaaaaa taaataaata aagatggttt taatatatgt tttagtttta tgattttagc 139020

atctttctga aatttttctc aaggcaagta aatttgtatc agttggtata ttggtaccca 139080

tctatgaaat aacttattag gaagatatct ctaaaataag atcactttgc ctaaaataaa 139140

ctgatatatt gatgttcaca gaatttttct tttaaccgac ttgataaatg cattattctt 139200

gacgtcaagt gatccacctt cctcagcctc ccaaagtgct gggattacac acatgagcca 139260

ccgcacctgg cattattctt ataaaaggtt aaatttctag ttaagtttaa tgtcctcttt 139320

gttcatgtac cattgcttat tttcttccct tcctactcac agtaatcatt cttatggtat 139380

gcacttttgt ttgcttattt ttatgtaatt gatattacgc tccattctgt acgttgtact 139440

ttcattcaca gtgagttttg gacattccta tgttcatcta tacagactta cttcatttta 139500

actacactgt agtattccgt atgtaatatt tactataact catcactgta gcagagcatc 139560

tcatagtgta tgtattactg ttttgccatt ttggtatcaa tgagtattta agtcatttgc 139620

agtttttccc tcttataccc agtattacag aggatctctt tttatatgct tctttgtacc 139680

aagaggcaga ttaaaaaatt tttttttgaa aaaatttttg aaaaaaaatg aaatgaagtc 139740

tcactatgtt gcccaggctg gtctcaaact cctaggctca agcaatcctt ccatcttggc 139800

ctcccaaagt gctggggtta caggcatgag ccaccatgcc tggcctacat tttaaatttt 139860

gatagctctt acaatttact ttgtaaagta tctgcatcat tttatgttct caccagtctt 139920

taataagaat acttcatact tttggctgga cacagtggct cacgcctgta atcccagcac 139980

tttgggaggc cgaggcgggc agatcaagag atcgagacca ccctggccaa tatggtgaaa 140040

ccctgtctct actaaaaata caaaaattag ctgggcgtgg tggcgcaccc gtagtcccag 140100

ctactcgaga ggctgagaca ggagaatcac ttgaacccgg gaggtggagg ttgcagtgaa 140160

cttagatcac accactgcac tccagcctag caacagagtg agactctgtc tcaaaaaaaa 140220

aaaagaatac ttcagactta attttttttc cagtcttaag tgtttgctaa tgagattgag 140280

tttcttttgg tatgtctctt gattgttcag gttttttctt ttatgaattg actgttcatc 140340

tctttttcac attatttctg ttgggtgatt ttattagtga cttgttaaaa ttctgtatat 140400

tttttcagca tgacacttca ttattcaaaa aaaaaaaaag attctctatg tttctcgata 140460

ctaatcattg gttggtaata ccttaaaaat aagaccctta ctgtattttt tgcttttttt 140520

tttttttttt tttttttttt tttgagatag agtcttgctc tgttgcccag gctggagtgc 140580

aatggtatga tctcggctct cagctcactg caactgcaac ctctacctcc ctgtttcaag 140640

caattctcct gccttagcct cccaagtagc tgggattaca ggcatccacc accacaccca 140700

gctaattttt gtatttttag tagagacagg gtttcaccat gttggccagg ctggtctcaa 140760

actactggcc tcaagtgatc cgcctgcctc ggcatcccaa agtactggga ttacaggcat 140820

gagccacagt gcctagccac tttttgcttt ttaactttgt tttatagtac tatagtttta 140880

gtataaacag atgtatgtat acacacaact atggctttat aatatgtttc agtcattgtt 140940

agagcaaggc ctaccttttg ggtgcttctt ttacaaaatt gtcttggcta ttcttgtgcc 141000

ttttttctta tttgtgaatt ttagaattgt gaattacctg ttgactcacc atgttttgta 141060

aactgaggat tttgaatgga attgcactca attaaagatt atcttgcttt ctgtgcagca 141120

atgttttatt tcaaataatc cctactttaa attacttagg atagctataa attgtgtttc 141180

tggctttcta gatttagatg aaacgcttta aattgattgt tttctcctaa atttaaaact 141240

gattgttaga agttaaagtc ttctgttcat tcttatttag gaagatgaca tttggaagag 141300

tcagtgactt ggggcaattc atccgagaat ctgagcctga acctgatgta aggaaatcaa 141360

aaggtttgtg gtgtttttat acttcatatt aagcctttac tcacattagt gattgactgt 141420

aagtcaaaga ccacttaagg tttaaactgt ttattttgta aagtaaccac tgtatctttc 141480

accttgtgtt tatagtcaga agtaagtaca agggcttcct gtagtcacat ctttatgcaa 141540

tctcctctga atcaaaagtt agtgaacttg ctttgccact ccagaaggca catgaatatg 141600

aaaaagcatt gtctattttc ttatttaatg gcaaaatacc cgacctaagt tggacttaat 141660

gtttgagacc gtttatttta ttaaattata ttttttctct tttctttttt ttttttgaga 141720

cagttcttgc tctgtcaccc agaccggagt gcagtggtct gaccgcacct cactgcaacc 141780

tctgcttcct aggttcaagc gattttcctg cctcatcctc ctgagtagct gggactacaa 141840

gtgcgcacca ccacacctgg ctaatttttg tatttttagc agagatgagg tttcaccacg 141900

ttggctaggc tggtctcata ctcctgacct caagcaatcc atccgccttg gcttcccaaa 141960

gtgctgggat tacaagtgtg agccaccatg cctggcctta ttaaattatt tttattaaat 142020

ttcctcaaga ttgatgaaag taatgaaata taaaagtaat gaaatatatg tggaaaatag 142080

actggattaa gaaaatgtgg cacatataca ccatggatac tatgcagcca taaaaaagga 142140

tgagttcatg tcctttgtag ggacatggat gaagctggaa accatcattc tgagcaaact 142200

gtctcaagga tagaaaacca aacaccgcat gctctcactc ataggtggga attgaacaat 142260

gagaacactt ggacacaggg tggggaacat cacacgctgg ggcctgtcgt ggggtggggg 142320

gctgggggag gaatagcatt aggagatata cctaatataa atgacgagtt aatgggtgca 142380

gcacaccaac atggtacatg tatacatatg taacaaagct gcacgttgtg cacatgtacc 142440

ctagaactta aagtataata aatttaaaaa aaataaatat atgtggaaaa tattaatagg 142500

tcaaaattca aattgttcat ttaatcagaa gagtagttta gtcaaatcca agggttagac 142560

aacagaaatc ttttttgtca agtgcattct ttgtgactga tttcattttc ttcctggttt 142620

acacaggaag atttcagaaa caaatgtgga tccgtgacag atggtatcta gaagttttta 142680

gtttggttga attgacagta ttttattgag taaaagatac taatttttgt aagaagaaaa 142740

attcaatttt gataagtatg tttaagatta agagctattg gccaggcgct gtggctcatg 142800

cctgtaatcc tagcactttg ggaagctgga gcaggtgggt cacgaggtca agagattgag 142860

accatcctgg ccaacatggt gaaaccctgt ctctactaaa ttagccaggc gtggtggcac 142920

atgcctgtgc acccgcctcc gggtttaagc gatcctactg cctcaggctc ctgagtagct 142980

gggattacag gcgccatggc taatttttgc atttttagta gagacagggt ttcactacat 143040

tggccaggct ggtctggtct caaactcctg acctcaggtg atctgcccgc cttagcctcc 143100

caaagtgctg ggattacagg catgattcac catgtctggc catttatctt attttctttt 143160

tttttttttt ttttgtttga gacggagtct tgctgtgtcg cccagagctg gagtgcaatg 143220

gtgcgatctc agctcactgc aacctctgcc tcctgggttc aagcaattct cctgcctcag 143280

tcttccaagt agctgggatt acaggcgcgt gccaccacat ctagctaatt tttgtatttt 143340

tagtagagac agggtttcac catgttggcc aggctggtct cggaactcct gacctcgtaa 143400

tctgcccacc tcggcctccc aaagtgctga gattacaagt gtgagccact gtgcccagcc 143460

atcttatttt ctttcttttt ttttgtcggg tgggaggggg acagagtcta gctctgtcgc 143520

caggcttggc tcactgcaac ctctgccccc caggttctag caattattct gcctcagcct 143580

cccaagtagc tgggattata ggcacctgcc accacgcctg gctaattttt tgttattttt 143640

agtagagatg gggttttgct atgttgacca tgctggcctc aagtgatccg cccaccttgg 143700

cctcccaaag tactgggctt acaggcgtga gcttgtattg ggtaaaagaa caatattggg 143760

ggctgcatgg tggttcatac ctgtaatctg agcactttgt gagactgaga tggaaggagt 143820

gttggagccc aggagggtga ggctgcggct gcagtgaatt gtgatcacgc cattgcactt 143880

ccacctaggt aatggagcaa gaccatgtct ctaaaaaaca aaacacaatt tttttaagga 143940

atactgggaa gaggtcagtg gtggttttag aacagaggaa gtgccagatg acctttgtga 144000

ggcattggcc aggaagaact ctacagtgtc tttaggtagc ttctgtccat aaggataatg 144060

gggtctcctc cccagtatta atagaaaatc tctgagctgt ttttttttgt ttgtttgttt 144120

tgtttttttt tcctgagatg gagtctctct ctgtcggcca ggctggagtg ctgtggcgcg 144180

atcttggctc actgcaagct ctgcctccca ggttcacacc attctcctgc ctcagcctcc 144240

caagtagctg ggactacagg tgtccaccac cacgcccagc taattttttg ttatttttag 144300

tagagatggg gtttcaccat gtcagccagg atggtctcga tctcctgacc tcgtgatccg 144360

ctcgcctctg ccttgcaaag tgctggagtt acaggcgtga gccaccgtgc ctggcctggt 144420

ttttttgttg ttgttattta tttatttatt tatttatttt ttgagacaga ctctcgctct 144480

gtcgcccggg ctggagtgta gtggcacgat gtcggctcac tgcaagctct gcctgccagg 144540

ttcaagccat tctcctgcct cagcctcctg agtagcaggg accacaggcg ctcgccacca 144600

cgcccggcta attttttgta tttttagaag agacggggtt tcaccgcatt agccaggatg 144660

gtctcgatct cctgatgtcg tgatccgccc acctcggcct cccaaagtgc tgggattaca 144720

ggtgtgagcc accgtgcctg gcctgatttt tttttttttt taatctggtc tcatacctct 144780

gacagctcat gaagaagtgc tcctgcttca tatgtatatg tgttagcata gtgttaacat 144840

agcataggtg ttcggtgttt gcagtttctg tttgttttat atgaattaag gtgtattatg 144900

agcagttgaa gatatatagg aaattttttc ccaaaccact atctctgctc gttctattca 144960

ttcagtctgt ttatgttatt ccttcattca ttcattttat agaacagtgg agtgcctact 145020

gtatgcatct attgttctgg gtcctgggga agaaaacaaa gttcctgctt tcatggaact 145080

tacattatat tggcggagac agtaacagac aaacaaatgt agcctgtgta catgtgttac 145140

atgaaaagca gggtaggggg ctgggagaga gtagtaggga gtgctatttt cgaggtggtt 145200

gtcaggaaag gcctcactga ggaggtggca ttttgagtag acctgagcgc agcgggggcg 145260

taagcccagg cagcatgtgg aggaagagtg ttcttggtga aaggaacaag gatagaggcc 145320

cgaagctaga gagctcagca tgatcaagga acagcaagcc ccgtgtggct ggaatggagt 145380

gagcaaagga atgagcagta gaaggtgagt gagttgggag gtcaccagag accatggcaa 145440

ggacttgaaa gtgtcaggga cacattggaa gttggagcag ggaaatgatg ggatttatgt 145500

tttgtttttg ttttatgttt agtgttttta agggattgct ctatcagcta tttggaaaat 145560

ttagtgtagg gcttcaagaa gagaagcaga gaaacaacat tcttgccata gtcatagtct 145620

aagtaaggga tgatggtggt gtggattagg ctggtagtgg aagaccagtc cagttcgggt 145680

tgtatttgaa ggtagaggca aaaagattat atttctacca gcaagcccat ctatgaagtt 145740

acttgtatta ttaatttaat tgagacatgc ccacataaac taataaatag gaatttctgc 145800

agtttggtta aacacccctg tatatcctgg ttcttctttt agttgtccag atgtctcttt 145860

aagtcaagta ttttttggtg gtgtaggagc ctagagattg aatttattca cccaaaaggc 145920

atttgagtga ttactatgtg ccaggcacta tgctgaatgc caaggatgta aataagaggg 145980

cgtagtctca gtctgtttta ctccagcttg gttccttttt aatgaccctg acttgttaag 146040

catatcagtt atcctacaga atgtttaatc ttctgtactt tcctggttgt gttatttagc 146100

ttatttctct ttccttgaca tttcttgtaa actggaagtt acacctatag tcttgatgat 146160

tcgtgttaca cattttagat tagaacacat catgtgttgt atatggtgtt tttgaaagcc 146220

tctctgtata ttggtctgta cattaaaatg ttgcctgaat ggatacacat aaaatttaac 146280

agtgattaca ttagagatga gaagaaagag gtgcctttta cttttcaata taccttttcc 146340

tctgcttttt gaactttctt gccctatgca tacgttattg cttaatcatc cacctcatct 146400

cttcccctgt ggctttctgt tgcatttgga atgaaatcta gcctctttgc tgttacctgt 146460

ggatgtccct tgctggcctc tatcacctta ctttgaacca ctcctttcat ggactgagct 146520

ctcattggac tatcttttat tcttttgctg aagtttcttc actttgagtg cctctgcagt 146580

tgctatttca tggctgtggc aagccctgcc atggctttca tgcaaggatg gttcctcctt 146640

ctcatctcaa tattatctct tcagagaggg accttcccaa ctccgatgat ctaaaatcct 146700

ttgtatatac cactcactac cacttctttc ttttcttttc cttttatctt tttttttttt 146760

tttttttttt gagatagggt cttgctctgt tgcccaggct ggaatcacga ctcactgcag 146820

cctcatcttc ttgggctcaa atgatcctct cacctcagcc tctcgagtag ctggaactgc 146880

aggcacacac caccatactt ggcttattat tttacttttt gtagagacag ggtttcacca 146940

aggctggtct caagctcctg ccgcaagcaa tccacatctc tcagcctccc aaagtattgg 147000

gattatagga gtgagccact actcctggcc tattttctta ttcactgtct aaaattatct 147060

tgttcattta tttacatact tgtttatagc ttatttctca gctggacatg gtgcctcaca 147120

cctgtaatct caatactttg ggaggctggg ttggagaatt ggttgagccc aggacttcaa 147180

gaccagcctg ggcaacaaag tgagaccctg tctataaaaa attgtttaaa aattagctgg 147240

gcatggtggc acatgcctgt ggtcccagct acttgggagg cagaggtggg agaatcgctt 147300

gggcccagga ggttgaggcg acggtgagcc atgattgtgc cactgcactc tagcctagtg 147360

acagagtgag accatgtgtc taaaaagtaa ataaaaatag tttctctttc atgactagaa 147420

tattacctct atgtgggcag ggagtttgtc tatactattt ggcactatat ttcctgattc 147480

tgaaattatg cctagcacat ggtaagtact ccttaaatat ttattgactg aattatttaa 147540

tacttaagaa tttcatttgg gattatctga gtggtaagat tacggattat atttatgtaa 147600

gaaaaaatca ttttttaaac ttggttgccc tttgccacac tgacatagac actaagtttt 147660

cttagccaga ttacttccga ggatactcac agaggccatt ctcttctcaa tccccaaata 147720

attgatattt cttagcactt tcaagctaat gcaattctta gatgatgtat ctgtgtatat 147780

catatcctca ttctacaaat gtagaaattg aagtctgggc acagtggctc tcacctgtaa 147840

tctcagcagt ttgggaggcc aaggcgagcg gatcactgag gacaagagtt aagaccagcc 147900

tggccaacat ggtaaagcct tgcctctatt aaaaatacaa caattagggc cgggcgtggt 147960

ggctcacgcc tataatccca gcacgttggg aggccaaggc aggcagatca cgaggtcagg 148020

agttcgagac catcctggct aacacagtga aaccccatct ctactaaaaa tacaaaaaat 148080

tagccaggca tggtggcacg cgcttgtagt cccagctatc gggaggctga ggcaggtgaa 148140

tcccttgaac ccgggaggcg gaggttgcaa tgagctgaga ttgcaccgct gaactccagc 148200

ctggtcaaca gagggagact ctgtctcaaa aaaaaaaaaa aaaaacaatt agccaggcgt 148260

ggtggcgggt acgagtacct gtaatcccag ctactaggga ggctgaggga ggagaatcac 148320

ttaaacccag gaggtggagt ttgcagcggg ctgataatgc accactacat tccagcctgg 148380

gcaacagagt gagactctgt cttaaaaaaa aaaaaaagaa agaaagaaat tgaggaatgt 148440

ggagattgtg gtctgtgatt tgttaggaat cacacagcag gttagtagca actacagggc 148500

tttggttcag aataccacct tgacaatggt ttgtttacag ttcggctccc cttcctctgc 148560

ctttctctcc ttccttattg agggcagctg gaaagaattt tcatcattta ctagcctata 148620

gctttaattt gagttttgaa accttgataa tagagcacag aggaaaagac tgagttttct 148680

ttttttgaga cagtcttgct ctatggccca ggctggagtg cagtgacacc atctcagctg 148740

gttgcaacct ctgcctccca ggttcaagca attctgcctc agcctctcga gtagctgaga 148800

ttacaggcac gtgtcaccac gcccagctaa ttttctgttt ttgtttcgtt ttgttttttt 148860

ctgagatgga gtcttgctct gtcacccagg ctggagtgca gtggtgcgat gttggctcac 148920

tcaaacctct gtctcctggg ttcaagcaat tcttctgcct cagcctcccc agtagctggg 148980

actacaggta cgtgccacca tccctagttc atttttgtat gtttagtaga gatggggttt 149040

cactatgttg accaggctgg tctcgaactc ctgatctcag gtgatctact cgtctcagtt 149100

tcccaaagtg ctgggattat tggcacacgc ctatttttgt atttttagta gagacggggt 149160

ttcaccatgt tggttagact ggtctcaaac ttctgacctc aagtgatttg cccgccccag 149220

cctcccaaag tgctgggatt acaggcgtga gccaccgtgc ccagccaaga ttgagttttg 149280

aaaagagcct tctgagatta tgagaagggc aagcaagata acttaagaag ttacattaaa 149340

atcatctaag agacagtgta acaagaagga attgtaaaat gatgttatga gcacgtgccc 149400

aatgtagtgg caatcccttg tgcttcgata cattggtggg agacaaaact gtacttaaat 149460

tgataaatcc cttacatgtc attttaagga gcttagactg actcccatca tgtagacatc 149520

agagatttct tttttttttt tttttttttt tttttttttt tttgtgacag agttttgctc 149580

ttgttgccga ggctggagtg caatggcgtg atctcggctc accacaacct ccacctccca 149640

ggttcaagca attctcctgc ctcagcctcc cgagtagctg ggattacagc catgcaccac 149700

cacgcctggc taattttgta tttttagtag agacggggtt tctccatgtt gtggctggtc 149760

tcgaactcct gacctcaggt gatcctcccg cctcagccac ccaaagttct gaaattacag 149820

gcgtgagcca ccgcgcccag cccagagatt tctaaacaga gttctaacca gatgcttttc 149880

cctgtcagta gaatgagaat gaattggagg tgggagagac tggcatgagg gacaccagtc 149940

agccagtgga attagctggt aatgttgata ggagaagaaa aagattcaaa gttaggtagt 150000

ggtagcaaga attagaggga aggtcggatt tatgatatgt ccaaggttga attctaaggt 150060

gaaatttggt ggcagatttc atgtgtaaat tgggaaggta gattgagttt ttttaacatg 150120

ggttttctaa catgtcaata gagtgactct gcaggggggc ctgacgagag aacagtgcat 150180

ggggtgattc aacagccagt tgagccttca tgcagagcat ttaacactgt gactctgtag 150240

actctggttg gcagtaaaat ttcattaaac caatatttaa acccttaggt aataataaaa 150300

attgagggaa aaggatccag gttttgtatt ttttatgaat tcagttattg aattaaacag 150360

gaccttgcct caagaaataa tctaccaaca attaacttgt tttaaagcaa agttaggaag 150420

tgagcatgtt caaattatta aataaaaaag taagctgtgt atttcattca tagaaataga 150480

ggctggccta cttcggatga ttctcagcat gtgattacag atgtgggctt atacatccta 150540

gggagttaag gcgtactctg gcttggatag agtagagctc tttgaaactc ttctctcacc 150600

cagctagttt atatagacta gagaactaga atgtagcagc atactctgtc ttagaagccc 150660

ttttatatag gagctggtct ggaaggtttg aaaacataac aaatgtgttg gtgtctccca 150720

atgtattgct agattcttac ccaagagcat tatcctggtt agggtttggt ttggttttgt 150780

tttgtttttt aatgtttgcc acaaactaac actagatgtt agttctttca tcaagtgagg 150840

agagtagaag aaaagtccag aactctgaaa caccttttca aaagtttttc aagccatgat 150900

gtttgcaagt taaatgctct gttatgtaag caatataatc agtttttatt aatgtaacat 150960

tccttagtgt tttggggtat cacacaaaaa agaatatcca tatctggaag caacagcttt 151020

taaataagag cattgtggtg gtggtggtga tagtggtttt tttttttttt tttgagttgg 151080

agtctcgctc tgttgcccag gttggagtgc agtggcacga tctcagctcg cttcaacctc 151140

tgctcccagg ttcaagcaat tcttctgcct cagcctcctg agtagctggg attataggca 151200

cctgctacca tgcctggctg atttttatta ttttagtaga gacaggtttc accatgttgg 151260

ccaggctggt cttgaactct taacctcagg tgaatcaccc acctcggcct cccaaagtgc 151320

tggaattaca ggcatgaacc accatggcca gccaaataag agcattttta atgtaaaatt 151380

atgcatgaaa tgtacattca attttgtctt tgtttactag gatccatgtt ctcacaagct 151440

atgaagaaat gggtgcaagg aaatactgat gaggtaaatc ctacctttag gataaaaaga 151500

tttctgttta taagtgccac cctcatgtaa gtgaggttta aaattttcct tttctttagg 151560

tcccatgttt aagcagcatg gcacatttat gttctcttac ccagaatgta ccaagaaagg 151620

gtggtccctt cttaacatct aacaattgcc tggtagtagc agtgaaggta tcttcagtca 151680

gaggctagga ccactgaagg atatacatgc attcaagttt ccatcagcca gcaggcatca 151740

gtaatcagtg tgtagatcaa aagctcaaat gtttccttcc ccactggcag ttttacttca 151800

agtagtggag gcttgctttt ttaatagtta attaagtaca ttgagagatg ggaggtgaaa 151860

aaaggaaaat gttttatttt gaccatctaa tatgaaagta gttcggtgtt aggtatccag 151920

tagttgacac tggaagacag ggaatgacat gttaatattc atagccagag ggtggcccag 151980

gttttttcgt acatgggaat gaaattctta tccaaataag tagaaattat gtgcgtaagc 152040

catttgttaa gagcactgag tatgtgcatc tcgatccatc taatgaataa ccattatcac 152100

cagtttaaat tattttcttt aggcccagga agagctagct tggaagattg ctaaaatgat 152160

agtcagtgac attatgcagc aggctcagta tgatcaaccg ttagagaaat ctacaaaggt 152220

aaggatgact tcgttttgtg taaactaaaa agtattattt tccaggtgta aaaataaaaa 152280

agaacataag gggtttcttt gcctttgaag gattaactgc tgtggggatt accttcttat 152340

cataagcaac tagaaaattg acaaactaaa tgaaacaact gtttgcatat attggacaat 152400

gggcaataca gggaaaccat ggaaaccaaa cagagcccag tagtcttgct gaacgaaaga 152460

gttaaatatc aaagttcagg ccaggtgcag tggctcacgc ctgtaatccc agcactttgg 152520

gaggccaagg cgggtgaatc acttgaggtc aggagttcaa gaccagcctg gccaacatgg 152580

tgaaaccctg tcttagccgg gtgtggtggc aggcacctgt aatcccaact atttgggagg 152640

ctgaggcagg agaatcgctt gaaccaggga ggcggaggtt gcagtgagcc gagatcacac 152700

cactgcactc cagcctgggc gacgagcgaa accccatttc aaaaaaaaaa tcaaagttca 152760

gagagctcaa tttgagtaga agttgtagga taaggtagca gaaaagagga agctgcccag 152820

aaagaaagcc gtagagatat ttagagagat tcccatggat ccttggccta ggagtgatct 152880

gtatatgtgt ggggtgaaaa cgcatgtgtc caggtagaga accccccaga aattagtagg 152940

ctgaatgatt gctggaacat agggctaaga aaagttcatg gccagaagga tctggccaga 153000

gtagagagac ttagtaatac acaaggcatt gggtagtgtc ttcacagagg ttatgcctta 153060

ctactgaaga taaattagtc ctagagtaca agcacctgaa ccaagtttca aagcaaattt 153120

ttaaagggtc aaattaccta acaactgcat gccaaaacaa aggcctaacc ctctttacag 153180

taacacaaca aaattcagca cttcacagtg taaagttaga atgtctgacg tccaggctgg 153240

gcgcagtggc tcatgcctgt aatcccagca ctttgggagg ccgaggcagg tagatgacct 153300

gaggtcagga gttcaagacc agcctggcta acatggtgca accccgtctc tattaaaaat 153360

acaaaaactt agccaggcat ggtggccggc acctgtgatc ccggctactt gggaggctga 153420

ggcaggagaa ttgcctgaac ccaggaggtg aaggttgcag tgagccgaga tcgcaccact 153480

gcactctggt ctgggcaaaa agagcaaaac tcaggctcaa aaaaaaaaaa gaatgtctga 153540

cgtcaatcac aaattaccaa gcatgacatg aagttgacct ataaccagga gaaaactcaa 153600

tctatagaaa cagacccaga tgtgagaaag atgatgaatt tagcagacaa agaccatcaa 153660

gtggctattt taaatattaa aaatatgttc aagtggccag gtgcagtggc tcatgcctgt 153720

aatcccagca ctttgggagg ccaaggtggg taggagttca agaccagctt ggccaatatg 153780

gtgaaacccc ttctctacta aaaatacaaa aaaattagct gggcatggtg gcaggtgcct 153840

atagtcccag ctatatggga ggctgaggca caagaatcac ttgaacccgg gaggtggagg 153900

ttgaggttgc agtaagccga gattgtgcca cttgtactcc agcctggaca acagagtgag 153960

actctgtctc aaaaaaaaaa aaaaaaaagt taaagaaaac aagagtataa tgagaaaaat 154020

gcaaaatagt tttaaaagaa ccaaatggaa tttcttaaaa taaaaaatac cagaaatggg 154080

ggccgggcgt ggtagctcac gtctataatc ccagcacttt gtgggggctg aggcaggcag 154140

atcacctgag atcggtagtt caaggccagc ctgaccaaca tggagaaacc tcatctctac 154200

taaaaataca aaattagctg ggcgtggtgg cgcattgcct gtaatcccag ctacttggga 154260

ggctgaggca ggagaattgc ttgaacccgg gaggcagagg ttgcggtgag ctgagattgc 154320

accagtgcac tccagcttgg gccacaagag tgaaactccg tctcaaaaaa aaaacaaaaa 154380

aaaacagtag actcgaagaa ctagctgagt ttttctttac tttaggcagt aagtgtgacc 154440

ttttgcaggt gactacttta gttcctcatg tcctcattag tagatcagag aaattcgaca 154500

ccaaaacccc aaaagaaaaa ccccttctaa tcctcattcc atgattttat gaatgcatga 154560

agtcctaggc ctgcgaagga atactcattc tctttatcct gtgttgatac ctctctgctt 154620

caacctccaa ctcgacattt gcctatagga tgtacttgga cattcagcat aaactacctc 154680

acaccattac tgaattgctt catgtgcaca tgtcccatgc cacaataccg gggaccttgt 154740

cttccgtgat atttgtccgc agtgctgtga ctacaggagg gagtcagtga atgtctgcat 154800

gtgtgtcttt accatccctc ttgaatatgc tctagggtta attcctagaa gtagaattac 154860

tctattgaaa attggcaata tttttcattc taatatctat tgccaacatg ggaaagcaag 154920

tctggatgcc agtccttgtt atatgcccct tgggtaagtt acgtaacctc tttaagcttc 154980

tgttcactca tattttaaca aggaaaatta caatatttta cctcacaaaa ttgtagtcag 155040

cttctggctg tcttaaactc tggtatatag taaacactaa gtgttggtgt ccatccttaa 155100

tttgtaataa taggtcactt gttagagaaa tgcaccttac cattttcttt tcttttcttt 155160

tttcagttat gactcaaaac ttgagataaa ggaaatctgc ttgtgaaaaa taagagaact 155220

tttttccctt ggttggattc ttcaacacag ccaatgaaaa cagcactata tttctgatct 155280

gtcactgttg tttccaggag agaatgggag acaatcctag acttccacca taatgcagtt 155340

acctgtaggc ataattgatg cacatgatgt tcacacagtg agagtcttaa agatacaaaa 155400

tggtattgtt tacattacta gaaaattatt agttttccaa tggcaataac ccatttatga 155460

gagtgtttta gcctactgga atagacaggg accacatcct ctgggaagca gataagcata 155520

gaactgatac ttgatgcaca ctcgtagtgg taactcatcc ctaatcagca ttgtaaagca 155580

ggtgccagag gtggtttgct ttgtccttcc aaagcaggtg agtcagcccc accgagagcc 155640

aggcagcttt gagtggcagc gtggtgctag cagcttcagc ggaacagggt gagagttaat 155700

tatgcagtct tcttgacagc ggcattaatt tggaaggaaa ctgacaagtc atgggtcaag 155760

tttcagtgac ttcctccttc ctctgatggc agtatatagt tttcacattt taattcctcc 155820

tcctgagatg cactatactt aaaaccattc tctcccctgc taacagaagg gtgtgaatct 155880

ggtttacttt gagcattagg atttgcccct ttggaattct gcactccagt tacttaactt 155940

tcccttcaga atacatgtgg aaagaaagaa agaaatagcg atgactccac ttttgcccct 156000

gtggcacctt gaacaaagca gttcttccca aattatactt tttttttttt taaataaggt 156060

gagcaggatg actggggaga gagaaacatt tgactttgac tgcctccccc attctttgct 156120

gtgagctgga aagtgtgcag ttggtcgtct ttcttctcct ttctttagga tagtaagaga 156180

ctcactcact gcacttctgc tcagttggct tctgcatcgg gatcacacag ccatcagcag 156240

gactgcccag ttggtgagca cactccattg accacgcggc gccagcgctt cctcaatgca 156300

catgattgag aggaaagaaa gttctcttag atgttactgc ttttgctcag actttgcaaa 156360

aaaaaaaata tatatatata tgtataaata tataattatt aatcactttt gtccttgaga 156420

aagtcttgaa tgaacagaga atttattcca ttgcaatatt tgattgtata gaggcacact 156480

gtttcatcga cagaagaagc aaaaaggctt tgtgtaagtt tttggtacta tgtaccacct 156540

ctgttattct tttaaagctg aagtattcat gtacttaaac catattatat ttaattgtgt 156600

ttgattttaa aatatatata tatgaattct atttaaaatt gtgtcaactt tctgctttca 156660

gggcatttat ggctcttctg ttgaaatata ttgatctttc caaatatttt catttgcttt 156720

ctaaaaaccc agaacatgag ccactactgg actttgcctt gtgtttgaag tgtatggcat 156780

aaacccaagg tttttattag tcatctatgc tgtgattaat tcattttgtt cttttaacaa 156840

aatatttcca tccacttcac attgcttcaa tctttaacag aaaagcaata taaaggttat 156900

agaataaaat gtggttttgg gcaactcttg ctgcctctgc atgttttgga ataacaattt 156960

ctacaagact ctaggctgtt taaactagtg ctttcagtta agataaattc taatcatttc 157020

tttgtatata cattttgtgc ttctgagcta gagatgccaa gtagttgtaa actgcttata 157080

aagagaatag cagcaaattt gagactcggc tacttttttc tgccccacct gctttgagac 157140

acagaagcgg agtgtggccc gaaattatta gccagattta atatttgatc taaagtaggt 157200

ccttgtactc attttaaagt tggaatttga ttcctccaac attgagcacc caccatgttc 157260

caggctctgt gcattgtgcc cacaaaataa gattccctgg tggagttttt atgggttcaa 157320

ataatcagtt gaacaccctt catctttatc atgttgttga cattgacaca aattgtttaa 157380

aaagaaaaga tattagagag aaagtggtac ctttgtaact tgatgtgtct tcatcattcg 157440

gtaagatttg atgaaagtaa aaagcaaatg tcagccaaat ccagtgaaca gcaataaaac 157500

agggagtaac tttttataac tttttctact tggatttcaa cattcagtag agcttttcga 157560

aatgtaagta gtttacagta ctggaggttt gactagttca gtaggaattt ggaggggaag 157620

gtcattctga attgtaacaa agtacaaact tctttgctgt tttatttaag tactgagagc 157680

taagcacctg atgaagtgac tgacctctct ccagtgacag tgtttgggta cctgcctgac 157740

ttcaggagtg gggtttatgt ttctacacag tgaccttttc tctcgccctc tcctccctct 157800

tgcccacaca ccagttgatt ggacctgggt tgaactcctg atccagacag gcccaagaca 157860

gttcttaatg ttaagaattt tggggccggg cacggtggct catgcctgta attgcaacac 157920

tttgggaggc cgagacaggc ggatcacttg aggtcagggg ttcgaggcca gcctggccaa 157980

catggtgaaa ccctgtcttt actaaaaata caaaaattag ctgggcatgg tggcgcacgc 158040

ctgtaatccc agctacgtgg gtggctgaga caggggaatc gcttgaacct ggaggcggag 158100

gttgtgcaat gagccgagac cgtgtcactg cattccagcc tgggtgacag agggagactc 158160

tgtctccaaa aataaaaata agaaaaagaa ttttgggcta ggtgcagtgg ctcacgcctg 158220

taattacagc attttggaag gcccaagatg ggcagatcac ttgaggacag gagttcgaga 158280

ccagcctgga caacatggtg aaactccatc tctactaaaa agacaaaagt tagccagatg 158340

tggtgatggg cacctataat cctagctcct cgggaggctg gggcaggaga atcacttgaa 158400

cccaggaagc agagattgca gtgagccaag atcacatctc tgcactccag cctgggcaac 158460

agagcaagac tctgtctcaa aaaaaaaaga atttggccag gcgcagtggt tcacgcctgt 158520

aatcccagca ctttgggagg ccaaggcagg cagatcacga ggtcaggaga tcgagattgt 158580

cctggctaac atggtgaaac cctgtctcta ctaaaaatac aaaacattag ccgggtgtgg 158640

tggtgggcac ctgtagtccc agctactagg gaggctgagg cagaggaagg atgtgaaccc 158700

aggaggcgga gcttgcagta agccaagatc gtgccactgc actacagtct gggcgacaga 158760

gtgagactcc gtctcaaaaa aaaaaagaat tttggccggg tgcggtggca catgcctgta 158820

gtcccagcac tttgggagac caaagtgggc ggattacctg aggtcaggag ttcaagacca 158880

gtccggccaa tatggcgaaa ccctgtctct tactaaaaaa aatacaaaaa ttagccaggt 158940

gtggtggcgg gcacctgggg aggctgaggc agggagaaat gcttgaaccg gggaggcaga 159000

ggttgcagta agccaagatc gtgccactgc actccagagc aagactcttt ctcaaaaaaa 159060

aaaaaaaaag aattttgcat ggggaaggag agatactgtt caccatctgg aatggtgctt 159120

ggatgtggca cttacaaaat caggagccag cactgcatgg acaaacagaa gcatgtgggc 159180

ctgagatagc aggtaccttg ataaccctga agacatcctt ggtttctgca tctattcctg 159240

catccttgca ttggactaca ttaatctgtc agttatcctt ataatgattt ttgatttttt 159300

ttttttgaga tggagtttcg ctcttgttgc ccaggctgga gtgcaatggc acgatctcgg 159360

ctcaccacaa cctccacctc ccaggttcaa gtgattctgc tgcctcagcc tcctgagtaa 159420

ctgggattac aggcatgcgc caccacacct ggctaatttt gtatttttag tagagacggg 159480

gtttctccat gttggtcagg ctggtctcga actcccaacc tcaggtgatc accctgtctc 159540

ggcctcccaa agtgctggga ttacaggcgt aagccatggt acccggtctg ttttttgatt 159600

ttttgaaacc agtctgaagt gagttttttt aattacgtga aaggagtttg gctaaaatac 159660

tgccatactg ccctaatgcc taatgattat gtattctcag catgtctgca aagtactgct 159720

gatttctgga gaataatttt tctttagtaa acttcactta agtcgtcatg tgtattctct 159780

caaaatggta tcctaaccta atggagctaa aagacacccc ttgtttttat aacaagcagt 159840

tactgaggcc caggaagggg agaagtccct ggcttgtgag atgatcacca ttagaactca 159900

ggcctgggcc agtgcctttt catgcttctc agatccttcc aaagaataat gaagattata 159960

accgctttta gcaattgtaa taaacccaga aatagaaagc tttttggtta gagtactggt 160020

agaagtttgg cgggagagat aatttttaca aaatttgtaa atacctgcca attctatata 160080

ctaggcaagg tctctggcct tgtaaaaccc ctcaaggtta caactttggt ggcccacact 160140

aatagttacc cactgaggcc ctctccgggt gaacattgag cactagagga agcccctctg 160200

cttgggcagg actgggcgtg gtgcagagta ggagcggtga tactgtggat tctgggcagg 160260

tggagatggc cagtgatgtc caataaagga cactggaggg agcagtgtga gtaaaggccc 160320

tgagggcatt catgttcagg gagggttgct gcccactggc ttgcttggca cacaggagag 160380

tgggtattcc tgccttagta actttatgta aacaagtatt tcctcagtct gttcctctca 160440

aactgcctgc tctggcacat tcagaatgtc acagaactca cctggatgca ttcagcccct 160500

tgcctaaagg tgacagtgca tctccttccc caccccaccc ctcataccac tgaagcacct 160560

gtcagactgg cccagtctgt gggcaaggag cctagagagg gcttagtttc agcttgaaag 160620

gagctgggat ttaccaagaa gcaaatgaga gacgaggatt gcaacaactg tgccatttcc 160680

ccagcttcag ctgactcctg tatattgact gtgccttcag actcatccgt aagtgacccc 160740

aggctggcct ctcccacatc acagtaagaa ttccacacac catacaactt ggaaagaggc 160800

tccagctgaa ggaagcccca cacttctttc aagtttttct tagtcttctc ttcttggcaa 160860

agagtacctt ttgtttcttc taattatgta actattggtt tagtaaatat tcacccattc 160920

agtcaccctg taagtggcag gcactgttta cagggacaca ggaaggaata aaaacttgca 160980

ggcaccttgg agcttgcatt ctattgaaga ggtaatggaa gttgggatag cagctaaact 161040

atgctggtat tggccaggcg cagtggctca cacctgtaat cccagcactt tggaggccaa 161100

ggtgggcaga tcatgaagtc aggagatcga gaccatcctg gctaacatgg tgaaaccccg 161160

tctctactaa aagtaaaaaa aaaaattagc caggtgtggt ggcgggcgcc tgtagtccca 161220

gctacttggg aggctgaggc aggagaatgg tgtgaaccca ggaggcgaag attgcagtga 161280

gccgagatgg caccactgca ctccagcctg ggtgacagag cgagactctg tctcagaaaa 161340

aaaaaatatg ctggtagttt tgattcaaga tggcctttgg agcccatgat ttaggtctcg 161400

tacccaccaa ggtctactgg aaaacatcag gctctcctgc tatagaccca tagggagagc 161460

tgcagccgag agggggagct gaagagaagt gccccttctg tgtcctgtca gcctcatcct 161520

tccgcaagga ccagttgctg tgccactcca ttcacttgct gcaagactgg aggtttttcc 161580

tcaggtgttg agcacctggt ttacaagatg tcagcatctt gatgcctgag accatcaagg 161640

caagtctctg aacagggctt accttagagt aaggcttaga agaggccgta aagtcagtct 161700

cagctccgtg gctctgcaga gctttgggac atgtgaattc ttaaaaacaa gactattgta 161760

cagttactat atgcatgcag tataaaatta taaccttgga aaatcctagc tagctgttga 161820

gctaattcca taaagtaatc agctcctgag ttctgcagtg gtaataataa tcagcataat 161880

gagtaaacac tgtgtgtgcc aggcagcgtc tcatttgatc cttgtgataa tcttgtaagt 161940

actgattttc tcccttcttt aaacaaagtt tttttttttt ttttagagag ggtctcacta 162000

tgttgcccag gctagtcttg aattc 162025

<210> SEQ ID NO 37

<211> LENGTH: 1350

<212> TYPE: DNA

<213> ORGANISM: Homo Sapien

<220> FEATURE:

<221> NAME/KEY: CDS

<222> LOCATION: (213)...(920)

<300> PUBLICATION INFORMATION:

<308> DATABASE ACCESSION NUMBER: GenBank AJ242973

<309> DATABASE ENTRY DATE: 1999-10-26

<400> SEQUENCE: 37

gcggccgcgt cgacgtgaca gccggtacgc ccgggtttgg gcaacctcga ttacgggcgg 60

cctccaggcc cgccagcagc gccccgcgcc gcccgcccgc gcccctgccg ccccccggtt 120

ccggccgcgg accccactct ctgccgttcc ggctgcggct ccgctgccgg tagcgccgtc 180

ccccgggacc acccttcggc tggcgccctc cc atg ctc tcg gcc acc cgg agg 233

Met Leu Ser Ala Thr Arg Arg

1 5

gct tgc cag ctc ctc ctc ctc cac agc ctc ttt ccc gtc ccg agg atg 281

Ala Cys Gln Leu Leu Leu Leu His Ser Leu Phe Pro Val Pro Arg Met

10 15 20

ggc aac tcg gcc tcg aac atc gtc agc ccc cag gag gcc ttg ccg ggc 329

Gly Asn Ser Ala Ser Asn Ile Val Ser Pro Gln Glu Ala Leu Pro Gly

25 30 35

cgg aag gaa cag acc cct gta gcg gcc aaa cat cat gtc aat ggc aac 377

Arg Lys Glu Gln Thr Pro Val Ala Ala Lys His His Val Asn Gly Asn

40 45 50 55

aga aca gtc gaa cct ttc cca gag gga aca cag atg gct gta ttt gga 425

Arg Thr Val Glu Pro Phe Pro Glu Gly Thr Gln Met Ala Val Phe Gly

60 65 70

atg gga tgt ttc tgg gga gct gaa agg aaa ttc tgg gtc ttg aaa gga 473

Met Gly Cys Phe Trp Gly Ala Glu Arg Lys Phe Trp Val Leu Lys Gly

75 80 85

gtg tat tca act caa gtt ggt ttt gca gga ggc tat act tca aat cct 521

Val Tyr Ser Thr Gln Val Gly Phe Ala Gly Gly Tyr Thr Ser Asn Pro

90 95 100

act tat aaa gaa gtc tgc tca gaa aaa act ggc cat gca gaa gtc gtc 569

Thr Tyr Lys Glu Val Cys Ser Glu Lys Thr Gly His Ala Glu Val Val

105 110 115

cga gtg gtg tac cag cca gaa cac atg agt ttt gag gaa ctg ctc aag 617

Arg Val Val Tyr Gln Pro Glu His Met Ser Phe Glu Glu Leu Leu Lys

120 125 130 135

gtc ttc tgg gag aat cac gac ccg acc caa ggt atg cgc cag ggg aac 665

Val Phe Trp Glu Asn His Asp Pro Thr Gln Gly Met Arg Gln Gly Asn

140 145 150

gac cat ggc act cag tac cgc tcg gcc atc tac ccg acc tct gcc aag 713

Asp His Gly Thr Gln Tyr Arg Ser Ala Ile Tyr Pro Thr Ser Ala Lys

155 160 165

caa atg gag gca gcc ctg agc tcc aaa gag aac tac caa aag gtt ctt 761

Gln Met Glu Ala Ala Leu Ser Ser Lys Glu Asn Tyr Gln Lys Val Leu

170 175 180

tca gag cac ggc ttc ggc ccc atc act acc gac atc cgg gag gga cag 809

Ser Glu His Gly Phe Gly Pro Ile Thr Thr Asp Ile Arg Glu Gly Gln

185 190 195

act ttc tac tat gcg gaa gac tac cac cag cag tac ctg agc aag aac 857

Thr Phe Tyr Tyr Ala Glu Asp Tyr His Gln Gln Tyr Leu Ser Lys Asn

200 205 210 215

ccc aat ggc tac tgc ggc ctt ggg ggc acc ggc gtg tcc tgc cca gtg 905

Pro Asn Gly Tyr Cys Gly Leu Gly Gly Thr Gly Val Ser Cys Pro Val

220 225 230

ggt att aaa aaa taa ttgctcccca catggtgggc ctttgaggtt ccagtaaaaa 960

Gly Ile Lys Lys *

235

tgctttcaac aaattgggca atgcttgtgt gattcacaat cgtggcattt aaagtgcaca 1020

aagtacaaag gaatttatac agattgggtt taccgaagta taatctatag gaggcgcgat 1080

ggcaagttga taaaatgtga cttatctcct aataagttat ggtgggagtg gagctgtgcg 1140

gtttcctgtg tcttctgggg tctgagtgaa gatagcaggg atgctgtgtt cacccttctt 1200

ggtagaagct aaggtgtgag ctgggaggtt gctggacagg atgggggacc ccagaagtcc 1260

tttatctgtg ctctctgccc gccagtgcct tacaatttgc aaacgtgtat agcctcagtg 1320

actcattcgc tgaaatcctt cgctttacca 1350

<210> SEQ ID NO 38

<211> LENGTH: 235

<212> TYPE: PRT

<213> ORGANISM: Homo Sapien

<400> SEQUENCE: 38

Met Leu Ser Ala Thr Arg Arg Ala Cys Gln Leu Leu Leu Leu His Ser

1 5 10 15

Leu Phe Pro Val Pro Arg Met Gly Asn Ser Ala Ser Asn Ile Val Ser

20 25 30

Pro Gln Glu Ala Leu Pro Gly Arg Lys Glu Gln Thr Pro Val Ala Ala

35 40 45

Lys His His Val Asn Gly Asn Arg Thr Val Glu Pro Phe Pro Glu Gly

50 55 60

Thr Gln Met Ala Val Phe Gly Met Gly Cys Phe Trp Gly Ala Glu Arg

65 70 75 80

Lys Phe Trp Val Leu Lys Gly Val Tyr Ser Thr Gln Val Gly Phe Ala

85 90 95

Gly Gly Tyr Thr Ser Asn Pro Thr Tyr Lys Glu Val Cys Ser Glu Lys

100 105 110

Thr Gly His Ala Glu Val Val Arg Val Val Tyr Gln Pro Glu His Met

115 120 125

Ser Phe Glu Glu Leu Leu Lys Val Phe Trp Glu Asn His Asp Pro Thr

130 135 140

Gln Gly Met Arg Gln Gly Asn Asp His Gly Thr Gln Tyr Arg Ser Ala

145 150 155 160

Ile Tyr Pro Thr Ser Ala Lys Gln Met Glu Ala Ala Leu Ser Ser Lys

165 170 175

Glu Asn Tyr Gln Lys Val Leu Ser Glu His Gly Phe Gly Pro Ile Thr

180 185 190

Thr Asp Ile Arg Glu Gly Gln Thr Phe Tyr Tyr Ala Glu Asp Tyr His

195 200 205

Gln Gln Tyr Leu Ser Lys Asn Pro Asn Gly Tyr Cys Gly Leu Gly Gly

210 215 220

Thr Gly Val Ser Cys Pro Val Gly Ile Lys Lys

225 230 235

<210> SEQ ID NO 39

<211> LENGTH: 481

<212> TYPE: DNA

<213> ORGANISM: Homo Sapien

<300> PUBLICATION INFORMATION:

<308> DATABASE ACCESSION NUMBER: GenBank AW195104

<309> DATABASE ENTRY DATE: 1999-11-29

<400> SEQUENCE: 39

ggcattattg gactgtaggt ttttattaaa acaaacattt ctcatagctc taagcaaagc 60

attagaattc atcaagcgga ctcacatctt ttctctgcac agagaggggc tgaaaaggga 120

gagaaagtcc cttatgtatg tctagatttg gtaaagcgaa ggatttcagc gaatgagtca 180

ctgaggctat acacgtttgc aaattgtaag gcactggcgg gcagagagca cagataaagg 240

acttctgggg tcccccatcc tgtccagcaa cctcccagct cacaccttag cttctaccaa 300

gaagggtgaa cacagcatcc ctgctatctt cactcagacc ccagaaaacc cagggaaacc 360

cgacagctcc actcccacca taacttatta ggagataagt cacattttat caacttgcca 420

tcgcgcctcc tatagattat acttcggtaa acccaatctg tataaattcc tttgtacttt 480

g 481

<210> SEQ ID NO 40

<211> LENGTH: 390

<212> TYPE: DNA

<213> ORGANISM: Homo Sapien

<300> PUBLICATION INFORMATION:

<308> DATABASE ACCESSION NUMBER: GenBank AW874187

<309> DATABASE ENTRY DATE: 2000-05-22

<400> SEQUENCE: 40

ttttttttat tggactgtag gtttttatta aaacaaacat ttctcatagc tctaagcaaa 60

gcattagaat tcatcaagcg gactcacatc ttttctctgc acagagaggg ctgaaaaggg 120

agagaaagcc ccttatgtat gtctagattt ggtaaagcga aggatttcag cgaatgagtc 180

actgaggcta tacacgtttg caaattgtaa ggcactggcg ggcagagagc acagataaag 240

gacttttggg ggtcccccat tcctgtccag caacctccca gctcacacct tagcttctac 300

caagaagggg tgaacacagc atccctgcta tcttcactca gacccccaga agacacagga 360

aaccgcacag ctccactccc accataactt 390

<210> SEQ ID NO 41

<211> LENGTH: 43

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 41

agcggataac aatttcacac agggagctag cttggaagat tgc 43

<210> SEQ ID NO 42

<211> LENGTH: 22

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 42

gtccaatata tgcaaacagt tg 22

<210> SEQ ID NO 43

<211> LENGTH: 23

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 43

agcggataac aatttcacac agg 23

<210> SEQ ID NO 44

<211> LENGTH: 18

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 44

actgagcctg ctgcataa 18

<210> SEQ ID NO 45

<211> LENGTH: 21

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 45

tctcaatcat gtgcattgag g 21

<210> SEQ ID NO 46

<211> LENGTH: 43

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 46

agcggataac aatttcacac agggatcaca cagccatcag cag 43

<210> SEQ ID NO 47

<211> LENGTH: 23

<212> TYPE: DNA

<213> ORGANISM: oligonucleotide primer

<400> SEQUENCE: 47

agcggataac aatttcacac agg 23

<210> SEQ ID NO 48

<211> LENGTH: 18

<212> TYPE: DNA

<213> ORGANISM: Oligonucleotide primer

<400> SEQUENCE: 48

ctggcgccac gtggtcaa 18

<210> SEQ ID NO 49

<211> LENGTH: 20

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 49

tttctctgca cagagagggc 20

<210> SEQ ID NO 50

<211> LENGTH: 44

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 50

agcggataac aatttcacac agggctgaaa tccttcgctt tacc 44

<210> SEQ ID NO 51

<211> LENGTH: 23

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 51

agcggataac aatttcacac agg 23

<210> SEQ ID NO 52

<211> LENGTH: 18

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 52

ctgaaaaggg agagaaag 18

<210> SEQ ID NO 53

<211> LENGTH: 20

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 53

tcccaaagtg ctggaattac 20

<210> SEQ ID NO 54

<211> LENGTH: 22

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 54

gtccaatata tgcaaacagt tg 22

<210> SEQ ID NO 55

<211> LENGTH: 20

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Primer

<400> SEQUENCE: 55

cccacagcag ttaatccttc 20

<210> SEQ ID NO 56

<211> LENGTH: 18

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 56

gcgctcctgt cggtgcca 18

<210> SEQ ID NO 57

<211> LENGTH: 18

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 57

gcctgactgg tggggccc 18

<210> SEQ ID NO 58

<211> LENGTH: 15

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 58

catgcatgca cggtc 15

<210> SEQ ID NO 59

<211> LENGTH: 30

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 59

cagagagtac ccctcgaccg tgcatgcatg 30

<210> SEQ ID NO 60

<211> LENGTH: 15

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 60

catgcatgca cggtt 15

<210> SEQ ID NO 61

<211> LENGTH: 30

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 61

gtacgtacgt gccaactccc catgagagac 30

<210> SEQ ID NO 62

<211> LENGTH: 14

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 62

catgcatgca cggt 14

<210> SEQ ID NO 63

<211> LENGTH: 18

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 63

gcctgactgg tggggccc 18

<210> SEQ ID NO 64

<211> LENGTH: 26

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 64

gtgctgcagg tgtaaacttg taccag 26

<210> SEQ ID NO 65

<211> LENGTH: 28

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 65

cacggatccg gtagcagcgg tagagttg 28

<210> SEQ ID NO 66

<211> LENGTH: 19

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 66

actgggcatg tggagacag 19

<210> SEQ ID NO 67

<211> LENGTH: 18

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 67

gcactttctt gccatgag 18

<210> SEQ ID NO 68

<211> LENGTH: 14

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 68

tcagtcacga cgtt 14

<210> SEQ ID NO 69

<211> LENGTH: 14

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 69

cggataacaa tttc 14

<210> SEQ ID NO 70

<211> LENGTH: 37

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 70

caatttcatc gctggatgca atctgggcta tgagatc 37

<210> SEQ ID NO 71

<211> LENGTH: 37

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 71

caatttcaca cagcggatgc ttcttttggc tctgact 37

<210> SEQ ID NO 72

<211> LENGTH: 40

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 72

tcagtcacga cgttggatgc caataaaagt gactctcagc 40

<210> SEQ ID NO 73

<211> LENGTH: 37

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 73

cggataacaa tttcggatgc actgggagca ttgaggc 37

<210> SEQ ID NO 74

<211> LENGTH: 38

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 74

tcagtcacga cgttggatga gcagatccct ggacaggc 38

<210> SEQ ID NO 75

<211> LENGTH: 38

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 75

cggataacaa tttcggatgg acaaaatacc tgtattcc 38

<210> SEQ ID NO 76

<211> LENGTH: 36

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 76

tcagtcacga cgttggatgc agagcagctc cgagtc 36

<210> SEQ ID NO 77

<211> LENGTH: 32

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 77

cagcggtgat cattggatgc aggaagctct gg 32

<210> SEQ ID NO 78

<211> LENGTH: 38

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 78

tcagtcacga cgttggatgc ccacatgcca cccactac 38

<210> SEQ ID NO 79

<211> LENGTH: 35

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 79

cggataacaa tttcggatgc ccgtcaggta ccacg 35

<210> SEQ ID NO 80

<211> LENGTH: 37

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 80

tcagtcacga cgttggatgc ccacagtgga gcttcag 37

<210> SEQ ID NO 81

<211> LENGTH: 22

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 81

gctcatacct tgcaggatga cg 22

<210> SEQ ID NO 82

<211> LENGTH: 36

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 82

tcagtcacga cgttggatga ccagctgttc gtgttc 36

<210> SEQ ID NO 83

<211> LENGTH: 34

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 83

tacatggagt tcggggatgc acacggcgac tctc 34

<210> SEQ ID NO 84

<211> LENGTH: 40

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 84

tcagtcacga cgttggatgg ggaagagcag agatatacgt 40

<210> SEQ ID NO 85

<211> LENGTH: 29

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 85

gaggggctga tccaggatgg gtgctccac 29

<210> SEQ ID NO 86

<211> LENGTH: 30

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 86

tgaagcactt gaaggatgag ggtgtctgcg 30

<210> SEQ ID NO 87

<211> LENGTH: 38

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 87

cggataacaa tttcggatgc tgcgtgatga tgaaatcg 38

<210> SEQ ID NO 88

<211> LENGTH: 26

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 88

gatgaagctc ccaggatgcc agaggc 26

<210> SEQ ID NO 89

<211> LENGTH: 27

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 89

gccgccggtg taggatgctg ctggtgc 27

<210> SEQ ID NO 90

<211> LENGTH: 31

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide Template

<400> SEQUENCE: 90

cgcagggttt cctcgtcgca ctgggcatgt g 31

<210> SEQ ID NO 91

<211> LENGTH: 43

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Biotinylatd primer

<400> SEQUENCE: 91

tgcttatccc tgtagctacc ctgtcttggc cttgcagatc caa 43

<210> SEQ ID NO 92

<211> LENGTH: 42

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 92

agcggataac aatttcacac aggccatcac accgcggtac tg 42

<210> SEQ ID NO 93

<211> LENGTH: 44

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 93

cccagtcacg acgttgtaaa acgtcttggc cttgcagatc caag 44

<210> SEQ ID NO 94

<211> LENGTH: 42

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 94

agcggataac aatttcacac aggccatcac accgcggtac tg 42

<210> SEQ ID NO 95

<211> LENGTH: 20

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 95

ctccagctgg gcaggagtgc 20

<210> SEQ ID NO 96

<211> LENGTH: 17

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Oligonucleotide primer

<400> SEQUENCE: 96

cacttcagtc gctccct 17

<210> SEQ ID NO 97

<211> LENGTH: 23

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Biotinylated primer

<400> SEQUENCE: 97

cccagtcacg acgttgtaaa acg 23

<210> SEQ ID NO 98

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 98

cctttgagaa agggctctgc ttgagttgta gaaagaaccg ctgcaacaat ctgggctatg 60

agatcaataa agtcagagcc aaaagaagca gcaaaatgta 100

<210> SEQ ID NO 99

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 99

cctttgagaa agggctctgc ttgagttgta gaaagaaccg ctgcaacaat ctgggctatg 60

agatcagtaa agtcagagcc aaaagaagca gcaaaatgta 100

<210> SEQ ID NO 100

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 100

gaattatttt tgtgtttcta aaactatggt tcccaataaa agtgactctc agcgagcctc 60

aatgctccca gtgctattca tgggcagctc tctgggctca 100

<210> SEQ ID NO 101

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 101

gaattatttt tgtgtttcta aaactatggt tcccaataaa agtgactctc agcaagcctc 60

aatgctccca gtgctattca tgggcagctc tctgggctca 100

<210> SEQ ID NO 102

<211> LENGTH: 84

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 102

taataggact acttctaatc tgtaagagca gatccctgga caggcgagga atacaggtat 60

tttgtccttg aagtaacctt tcag 84

<210> SEQ ID NO 103

<211> LENGTH: 84

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 103

taataggact acttctaatc tgtaagagca gatccctgga caggcaagga atacaggtat 60

tttgtccttg aagtaacctt tcag 84

<210> SEQ ID NO 104

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 104

ctcaccatgg gcatttgatt gcagagcagc tccgagtccg tccagagctt cctgcagtca 60

atgatcaccg ctgtgggcat ccctgaggtc atgtctcgta 100

<210> SEQ ID NO 105

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 105

ctcaccatgg gcatttgatt gcagagcagc tccgagtcca tccagagctt cctgcagtca 60

atgatcaccg ctgtgggcat ccctgaggtc atgtctcgta 100

<210> SEQ ID NO 106

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 106

agcaaggact cctgcaaggg ggacagtgga ggcccacatg ccacccacta ccagggcacg 60

tggtacctga cgggcatcgt cagctggggc cagggctgcg 100

<210> SEQ ID NO 107

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 107

agcaaggact cctgcaaggg ggacagtgga ggcccacatg ccacccacta ccggggcacg 60

tggtacctga cgggcatcgt cagctggggc cagggctgcg 100

<210> SEQ ID NO 108

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Hom sapien

<400> SEQUENCE: 108

caataactct aatgcagcgg aagatgacct gcccacagtg gagcttcagg gcgtggtgcc 60

ccggggcgtc aacctgcaag gtatgagcat accccccttc 100

<210> SEQ ID NO 109

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 109

caataactct aatgcagcgg aagatgacct gcccacagtg gagcttcagg gcttggtgcc 60

ccggggcgtc aacctgcaag gtatgagcat accccccttc 100

<210> SEQ ID NO 110

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 110

ttgaagcttt gggctacgtg gatgaccagc tgttcgtgtt ctatgatcat gagagtcgcc 60

gtgtggagcc ccgaactcca tgggtttcca gtagaatttc 100

<210> SEQ ID NO 111

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 111

ttgaagcttt gggctacgtg gatgaccagc tgttcgtgtt ctatgatgat gagagtcgcc 60

gtgtggagcc ccgaactcca tgggtttcca gtagaatttc 100

<210> SEQ ID NO 112

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 112

ggataacctt ggctgtaccc cctggggaag agcagagata tacgtgccag gtggagcacc 60

caggcctgga tcagcccctc attgtgatct gggagccctc 100

<210> SEQ ID NO 113

<211> LENGTH: 100

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 113

ggataacctt ggctgtaccc cctggggaag agcagagata tacgtaccag gtggagcacc 60

caggcctgga tcagcccctc attgtgatct gggagccctc 100

<210> SEQ ID NO 114

<211> LENGTH: 80

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 114

tgaagcactt gaaggagaag gtgtctgcgg gagccgattt catcatcacg cagcttttct 60

ttgaggctga cacattcttc 80

<210> SEQ ID NO 115

<211> LENGTH: 80

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 115

tgaagcactt gaaggagaag gtgtctgcgg gagtcgattt catcatcacg cagcttttct 60

ttgaggctga cacattcttc 80

<210> SEQ ID NO 116

<211> LENGTH: 80

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 116

tccagatgaa gctcccagaa tgccagaggc tgctccccgc gtggcccctg caccagcagc 60

tcctacaccg gcggcccctg 80

<210> SEQ ID NO 117

<211> LENGTH: 80

<212> TYPE: DNA

<213> ORGANISM: Homo sapien

<400> SEQUENCE: 117

tccagatgaa gctcccagaa tgccagaggc tgctcccccc gtggcccctg caccagcagc 60

tcctacaccg gcggcccctg 80

<210> SEQ ID NO 118

<211> LENGTH: 48

<212> TYPE: DNA

<213> ORGANISM: Artificial Sequence

<220> FEATURE:

<223> OTHER INFORMATION: Hair pin structure

<400> SEQUENCE: 118

cagagagtac ccctcaaccg tgcatgcatg aaacatgcat gcacggtt 48

Claims

What is claimed is:

1. A high throughput method of determining frequencies of genetic variations, comprising:

selecting a healthy target population and a genetic variation to be assessed;

pooling a plurality of samples of biopolymers obtained from members of the population;

determining or detecting the biopolymer that comprises the variation by mass spectrometry;

obtaining a mass spectrum or a digital representation thereof; and

determining the frequency of the variation in the population.

2. The method of claim 1, wherein:

the variation is selected from the group consisting of an allelic variation, a post-translational modification, a nucleic modification, a label, a mass modification of a nucleic acid and methylation; and/or

the biopolymer is a nucleic acid, a protein, a polysaccharide, a lipid, a small organic metabolite or intermediate, wherein the concentration of biopolymer of interest is the same in each of the samples; and/or

the frequency is determined by assessing the method comprising determining the area under the peak in the mass spectrum or digital representation thereof corresponding to the mass of the biopolymer comprising the genomic variation.

3. The method of claim 2, wherein the method for determining the frequency is effected by determining the ratio of the signal or the digital representation thereof to the total area of the entire mass spectrum, which is corrected for background.