Asthma related genes

Asthma is a disease of reversible bronchial obstruction, characterized by airway inflammation, epithelial damage, airway smooth muscle hypertrophy and bronchial hyperreactivity. Many asthma symptoms can be controlled by medical intervention, but incidence of asthma-related death and severe illness continue to rise in the United States. The approximately 4,800 deaths in 1989 marked a 46 percent increase since 1980. As many as 12 million people in the United States have asthma, up 66 percent since 1980, and annually, the disease's medical and indirect costs are estimated at over $6 billion.
Two common subdivisions of asthma are atopic (allergic, or extrinsic) asthma and non-atopic (intrinsic) asthma. Atopy is characterized by a predisposition to raise an IgE antibody response to common environmental antigens. In atopic asthma, asthma symptoms and evidence of allergy, such as a positive skin test to common allergens, are both present. Non-atopic asthma may be defined as reversible airflow limitation in the absence of allergies.
The smooth muscle surrounding the bronchi are able to rapidly alter airway diameter in response to stimuli. When the response is excessive, it is termed bronchial hyperreactivity, a characteristic of asthma thought to have a heritable component. Studies have demonstrated a genetic predisposition to asthma by showing, for example, a greater concordance for this trait among monozygotic twins than among dizygotic twins. The genetics of asthma is complex, however, and shows no simple pattern of inheritance. Environment also plays a role in asthma development, for example, children of smokers are more likely to develop asthma than are children of non-smokers.
In recent years thousands of human genes have been cloned. In many cases, gene discovery has been based on prior knowledge about the corresponding protein, such as amino acid sequence, immunological reactivity, etc. This approach has been very successful, but is limited in some important ways. One limitation is that genes in these cases are identified based on knowledge of molecular level protein properties. For a large number of important human genes, however, there is little or no biochemical data concerning the encoded product. For example, genes that predispose to human diseases, such as cystic fibrosis, Huntington's disease, etc. are of interest because of their phenotypic effect. Biochemical characterization of such genes may be secondary to genetic characterization.
A solution to this impasse has been found in combining classical genetic mapping with the ability to identify genes and, if necessary, to sequence large regions of chromosomes. Population and family studies enable genes associated with a trait of interest to be localized to a relatively small region of a chromosome. At this point, physical mapping can be used to identify candidate genes, and various molecular biology techniques used to pick out mutated genes in affected individuals. This "top-down" approach to gene discovery has been termed positional cloning, because genes are identified based on position in the genome.
Positional cloning is now being applied to complex genetic diseases, which affect a greater fraction of humanity than do the more simple and usually rarer single gene disorders. Such studies must take into account the contribution of both environmental and genetic factors to the development of disease, and must allow for contributions to the genetic component by more than one, and potentially many, genes. The clinical importance of asthma makes it of considerable interest to characterize genes that underlie a genetic predisposition to this disease. Positional cloning provides an approach to this goal.
Relevant Literature
The symptoms and biology of asthma are reviewed in Chanez et al. (1994) Odyssey 1:24-33. A review of bronchial hyperreactivity may be found in Smith and McFadden (1995) Ann. Allergy. Asthma and Immunol. 74:454. Moss (1989) Annals of Allergy 63:566 review the allergic etiology and immunology of asthma.
The genetic dissection of complex traits is discussed in Lander and Schork (1994) Science 265:2037-2048. Genetic mapping of candidate genes for atopy and/or bronchial hyperreactivity is described in Postma et al. (1995) N.E.J.M. 333:894; Marsh et al. (1994) Science 264:1152; and Meyers et al. (1994) Genomics 23:464. Lawrence et al. (1994) Ann. Hum. Genet. 58:359 discuss an approach to the genetic analysis of atopy and asthma. Genetic linkage between the alpha subunit of the T cell receptor and IgE reactions has been noted by Moffat et al. (1994) The Lancet 343:1597. Caraballo and Hernandez (1990) Tissue Antigens 35:182 noted an association between HLA alleles and allergic asthma. Evidence of linkage of atopy to markers on chromosome 11q has been seen in some British asthma families (Cookson et al. (1989) Lancet i:1292-1295; Young et al. (1991) J. Med. Genet. 29:236, but not in other British families (Lympany et al. (1992) Clin. Exp. Allergy 22:1085-1092) or in families from Minnesota or Japan (Rich et al. (1992) Clin. Exp. Allergy 22:1070-1076; and Hizawa et al. (1992) Clin. Exp. Allergy 22:1065).
The association of a polymorphism for the Fc.epsilon.RI-.beta. gene and risk of atopy is described in Hill et al. (1995) B.M.J. 311:776; Hill and Cookson (1996) Human Mol. Genet. 5:959; and Shirakawa et al. (1994) Nature Genetics 7:125; an association of Fc.epsilon.RI-.beta. with bronchial hyperreactivity is described in van Herwerden (1995) The Lancet 346:1262.
Collections of polymorphic markers from throughout the human genome have been tested for linkage to asthma, described in Meyers et al. (1996) Am. J. Hum. Genet. 59:A228 and Daniels et al. (1996) Nature 383:247-250. No linkage to human chromosome 11p was detected in these studies.
SUMMARY OF THE INVENTION
Human genes associated with a genetic predisposition to asthma are provided. The genes, herein termed ASTH1I and ASTH1J, are located close to each other on human chromosome 11p, have similar patterns of expression, and common sequence motifs. The nucleic acid compositions are used to produce the encoded proteins, which may be employed for functional studies, as a therapeutic, and in studying associated physiological pathways. The nucleic acid compositions and antibodies specific for the protein are useful as diagnostics to identify a hereditary predisposition to asthma.

BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1: Genomic organization of the ASTH1I and ASTH1J genes. The sizes of the exons are not to scale. Alternative exons are hatched. The direction of transcription is indicated below each gene.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS
The provided ASTH1 genes and fragments thereof, encoded protein, ASTH1 genomic regulatory regions, and anti-ASTH1 antibodies are useful in the identification of individuals predisposed to development of asthma, and for the modulation of gene activity in vivo for prophylactic and therapeutic purposes. The encoded ASTH1 protein is useful as an immunogen to raise specific antibodies, in drug screening for compositions that mimic or modulate ASTH1 activity or expression, including altered forms of ASTH1 protein, and as a therapeutic.
Asthma, as defined herein, is reversible airflow limitation in a patient over a period of time. The disease is characterized by increased airway responsiveness to a variety of stimuli, and airway inflammation. A patient diagnosed as asthmatic will generally have multiple indications over time, including wheezing, asthmatic attacks, and a positive response to methacholine challenge, i.e. a PC.sub.20 on methacholine challenge of less than about 4 mg/ml. Guidelines for diagnosis may be found in the National Asthma Education Program Expert Panel. Guidelines for diagnosis and management of asthma. National Institutes of Health, 1991; Pub. #91-3042. Atopy, respiratory infection and environmental predisposing factors may also be present, but are not necessary elements of an asthma diagnosis. Asthma conditions strictly related to atopy are referred to as atopic asthma.
The human ASTH1I and ASTH1J gene sequences are provided, as are the genomic sequences 5' to ASTH1J. The major sequences of interest provided in the sequence listing are as follows:
______________________________________ASTH1J5' Genomic Region DNA (SEQ ID NO:1)ASTH1J alt1 cDNA (SEQ ID NO:2)ASTH1J alt2 cDNA (SEQ ID NO:3)ASTH1J alt3 cDNA (SEQ ID NO:4)ASTH1J protein protein (SEQ ID NO:5)ASTH1l alt1 cDNA (SEQ ID NO:6)ASTH1l alt1 protein protein (SEQ ID NO:7)ASTH1l alt2 cDNA (SEQ ID NO:8)ASTH1l alt2 protein protein (SEQ ID NO:9)ASTH1l alt3 cDNA (SEQ ID NO:10)ASTH1l alt3 protein protein (SEQ ID NO:11)CAAT box "A" form DNA (SEQ ID NO:12)CAAT box "G" form DNA (SEQ ID NO:13)ASTH1J5' promoter region DNA (SEQ ID NO:14)Mouse asth1j cDNA (SEQ ID NO:338)Mouse asth1j protein (SEQ ID NO:339)Polymorphisms DNA (SEQ ID NO:16-159)Microsatellite flanking sequences DNA (SEQ ID NO:160-281)Microsatellite repeats DNA (SEQ ID NO:282-292)Intron-Exon boundaries DNA (SEQ ID NO:293-335)______________________________________
The ASTH1 locus has been mapped to human chromosome 11p. The traits for a positive response to methacholine challenge and a clinical history of asthma were shown to be genetically linked in a genome scan of the population of Tristan da Cunha, a single large extended family with a high incidence of asthma (discussed in Zamel et al. (1996) Am. J. Respir. Crit. Care Med. 153:1902-1906). The linkage finding was replicated in a set of Canadian asthmatic families. The region of strongest linkage was the marker D11S907 on the short arm of chromosome 11. Additional markers were identified from the four megabase region surrounding D11 S907 from public databases and by original cloning of new polymorphic microsatellite markers. Refinement of the region of interest was obtained by genotyping new markers in the studied populations, and applying the transmission disequilibrium test (TDT), which reflects the level of association between marker alleles and disease status. TDT curves were superimposed on the physical map. Molecular genetic techniques for gene identification were applied to the region of interest. A one megabase genomic region was sequenced to high accuracy, and the resulting data used for the sequence-based prediction of genes and determination of the intron/exon structure of genes in the region.
Nucleic Acid Compositions
ASTH1I produces a 2.8 kb mRNA expressed at high levels in trachea and prostate, and at lower levels in lung and kidney and possibly other tissues. ASTH1I cDNA clones have also been identified in prostate, testis and lung libraries. Sequence polymorphisms are shown in Table 3. ASTH1I has at least three alternate forms denoted as alt1, alt2, and alt3. The alternative splicing and start codons give the three forms of ASTH1I proteins different amino termini. The ASTH1I proteins, alt1, alt2 and alt3 are 265, 255 and 164 amino acids in length, respectively.
A domain of the ASTH1I and ASTH1J proteins is similar in sequence to transcription factors of the ets family. The ets family is a group of transcription factors that activate genes involved in a variety of immunological and other processes. The family members most similar to ASTH1I and ASTH1J are: ETS1, ETS2, ESX, ELF, ELK1, TEL, NET, SAP-1, NERF and FLI. The ASTH1I and ASTH1J proteins show similarity to each other. Over the ets domain they are 66% similar (ie. have amino acids with similar properties in the same positions) and 46% identical to each other. All forms of ASTH1I and ASTH1J have a helix turn helix motif, characteristic of some transcription factors, located near the carboxy terminal end of the protein.
ASTH1J produces an approximately 6 kb mRNA expressed at high levels in the trachea, prostate and pancreas and at lower levels in colon, small intestine, lung and stomach. ASTH1J has at least three forms, consisting of the alt1, alt2 and alt3 forms. The open reading frame is identical for the three forms, which differ only in the 5' UTR. The protein encoded by ASTH1J is 300 amino acids in length.
Mouse coding region sequence of asth1j is provided in SEQ ID NO:326, and the amino acid sequence is provided in SEQ ID NO:327. The mouse and human proteins have 88.4% identity throughout their length. The match in the ets domain is 100%. The mouse cDNA was identified by hybridization of a full-length human cDNA to a mouse lung cDNA library (Stratagene).
The term "ASTH1 genes" is herein used generically to designate ASTH1I and ASTH1J genes and their alternate forms. The two genes lie in opposite orientations on a native chromosome, with the 5' regulatory sequences between them. Part of the genomic sequence between the two coding regions is provided as SEQ ID NO:1. The term "ASTH1 locus" is used herein to refer to the two genes in all alternate forms and the genomic sequence that lies between the two genes. Alternate forms include splicing variants, and polymorphisms in the sequence. Specific polymorphic sequences are provided in SEQ ID NOs:16-159. For some purposes the previously known EST sequences described herein may be excluded from the sequences defined as the ASTH1 locus.
The DNA sequence encoding ASTH1 may be cDNA or genomic DNA or a fragment thereof. The term "ASTH1 gene" shall be intended to mean the open reading frame encoding specific ASTH1 polypeptides, introns, as well as adjacent 5' and 3' non-coding nucleotide sequences involved in the regulation of expression, up to about 1 kb beyond the coding region, but possibly further in either direction. The gene may be introduced into an appropriate vector for extrachromosomal maintenance or for integration into the host.
The term "cDNA" as used herein is intended to include all nucleic acids that share the arrangement of sequence elements found in native mature mRNA species, where sequence elements are exons and 3' and 5' non-coding regions. Normally mRNA species have contiguous exons, with the intervening introns removed by nuclear RNA splicing, to create a continuous open reading frame encoding the ASTH1 protein.
The genomic ASTH1 sequence has non-contiguous open reading frames, where introns interrupt the protein coding regions. A genomic sequence of interest comprises the nucleic acid present between the initiation codon and the stop codon, as defined in the listed sequences, including all of the introns that are normally present in a native chromosome. It may further include the 3' and 5' untranslated regions found in the mature mRNA. It may further include specific transcriptional and translational regulatory sequences, such as promoters, enhancers, etc., including about 1 kb, but possibly more, of flanking genomic DNA at either the 5' or 3' end of the transcribed region. The genomic DNA may be isolated as a fragment of 100 kbp or smaller; and substantially free of flanking chromosomal sequence.
Genomic regions of interest include the non-transcribed sequences 5' to ASTH1J, as provided in SEQ ID NO:1. This region of DNA contains the native promoter elements that direct expression of the linked ASTH1J gene. Usually a promoter region will have at least about 140 nt of sequence located 5' to the ASTH1 gene and further comprising a TATA box and CMT box motif sequence (SEQ ID NO:14, nt. 597-736). The promoter region may further comprise a consensus ets binding motif, (C/A)GGA(A/T) (SEQ ID NO:14, nt 1-5). A region of particular interest, containing the ets binding motif, TATA box and CAAT box motifs 5' to the ASTH1J gene, is provided in SEQ ID NO:14. The position of SEQ ID NO:14 within the larger sequence is SEQ ID NO:1, nt 60359-61095. The promoter sequence may comprise polymorphisms within the CAAT box region, for example those shown in SEQ ID NO:12 and SEQ ID NO:13, which have been shown to affect the function of the promoter. The promoter region of interest may extend 5' to SEQ ID NO:14 within the larger sequence, e.g. SEQ ID NO:1, nt 59000-61095; SEQ ID NO:1, nt 5700-61095, etc.
The sequence of this 5' region, and further 5' upstream sequences and 3' downstream sequences, may be utilized for promoter elements, including enhancer binding sites, that provide for expression in tissues where ASTH1J is expressed. The tissue specific expression is useful for determining the pattern of expression, and for providing promoters that mimic the native pattern of expression. Naturally occurring polymorphisms in the promoter region are useful for determining natural variations in expression, particularly those that may be associated with disease. See, for example, SEQ ID NO:12 and 13. Alternatively, mutations may be introduced into the promoter region to determine the effect of altering expression in experimentally defined systems. Methods for the identification of specific DNA motifs involved in the binding of transcriptional factors are known in the art, e.g. sequence similarity to known binding motifs, gel retardation studies, etc. For examples, see Blackwell et al. (1995) Mol Med 1: 194-205; Mortlock et al. (1996) Genome Res. 6: 327-33; and Joulin and Richard-Foy (1995) Eur J Biochem 232: 620-626.
The regulatory sequences may be used to identify cis acting sequences required for transcriptional or translational regulation of ASTH1 expression, especially in different tissues or stages of development, and to identify cis acting sequences and trans acting factors that regulate or mediate ASTH1 expression. Such transcription or translational control regions may be operably linked to a ASTH1 gene in order to promote expression of wild type or altered ASTH1 or other proteins of interest in cultured cells, or in embryonic, fetal or adult tissues, and for gene therapy.
The nucleic acid compositions of the subject invention may encode all or a part of the subject polypeptides. Fragments may be obtained of the DNA sequence by chemically synthesizing oligonucleotides in accordance with conventional methods, by restriction enzyme digestion, by PCR amplification, etc. For the most part, DNA fragments will be of at least 15 nt, usually at least 18 nt, more usually at least about 50 nt. Such small DNA fragments are useful as primers for PCR, hybridization screening, etc. Larger DNA fragments, i.e. greater than 100 nt are useful for production of the encoded polypeptide. For use in amplification reactions, such as PCR, a pair of primers will be used. The exact composition of the primer sequences is not critical to the invention, but for most applications the primers will hybridize to the subject sequence under stringent conditions, as known in the art. It is preferable to choose a pair of primers that will generate an amplification product of at least about 50 nt, preferably at least about 100 nt. Algorithms for the selection of primer sequences are generally known, and are available in commercial software packages. Amplification primers hybridize to complementary strands of DNA, and will prime towards each other.
The ASTH1 genes are isolated and obtained in substantial purity, generally as other than an intact mammalian chromosome. Usually, the DNA will be obtained substantially free of other nucleic acid sequences that do not include an ASTH1 sequence or fragment thereof, generally being at least about 50%, usually at least about 90% pure and are typically "recombinant", i.e. flanked by one or more nucleotides with which it is not normally associated on a naturally occurring chromosome.
The DNA sequences are used in a variety of ways. They may be used as probes for identifying ASTH1 related genes. Mammalian homologs have substantial sequence similarity to the subject sequences, i.e. at least 75%, usually at least 90%, more usually at least 95% sequence identity with the nucleotide sequence of the subject DNA sequence. Sequence similarity is calculated based on a reference sequence, which may be a subset of a larger sequence, such as a conserved motif, coding region, flanking region, etc. A reference sequence will usually be at least about 18 nt long, more usually at least about 30 nt long, and may extend to the complete sequence that is being compared. Algorithms for sequence analysis are known in the art, such as BLAST, described in Altschul et al. (1990) J Mol Biol 215:403-10.
Nucleic acids having sequence similarity are detected by hybridization under low stringency conditions, for example, at 50.degree. C. and 10.times.SSC (0. 9 M saline/0.09 M sodium citrate) and remain bound when subjected to washing at 55.degree. C. in 1.times.SSC. Sequence identity may be determined by hybridization under stringent conditions, for example, at 50.degree. C. or higher and 0.1.times.SSC (9 mM saline/0.9 mM sodium citrate). By using probes, particularly labeled probes of DNA sequences, one can isolate homologous or related genes. The source of homologous genes may be any species, e.g. primate species, particularly human; rodents, such as rats and mice, canines, felines, bovines, ovines, equines, yeast, Drosophila, Caenhorabditis, etc.
The DNA may also be used to identify expression of the gene in a biological specimen. The manner in which one probes cells for the presence of particular nucleotide sequences, as genomic DNA or RNA, is well established in the literature and does not require elaboration here. mRNA is isolated from a cell sample. mRNA may be amplified by RT-PCR, using reverse transcriptase to form a complementary DNA strand, followed by polymerase chain reaction amplification using primers specific for the subject DNA sequences. Alternatively, mRNA sample is separated by gel electrophoresis, transferred to a suitable support, e.g. nitrocellulose, nylon, etc., and then probed with a fragment of the subject DNA as a probe. Other techniques, such as oligonucleotide ligation assays, in situ hybridizations, and hybridization to DNA probes arrayed on a solid chip may also find use. Detection of mRNA hybridizing to the subject sequence is indicative of ASTH1 gene expression in the sample.
The subject nucleic acid sequences may be modified for a number of purposes, particularly where they will be used intracellularly, for example, by being joined to a nucleic acid cleaving agent, e.g. a chelated metal ion, such as iron or chromium for cleavage of the gene; or the like.
The sequence of the ASTH1 locus, including flanking promoter regions and coding regions, may be mutated in various ways known in the art to generate targeted changes in promoter strength, sequence of the encoded protein, etc. The DNA sequence or product of such a mutation will be substantially similar to the sequences provided herein, i.e. will differ by at least one nucleotide or amino acid, respectively, and may differ by at least two but not more than about ten nucleotides or amino acids. The sequence changes may be substitutions, insertions or deletions. Deletions may further include larger changes, such as deletions of a domain or exon. Other modifications of interest include epitope tagging, e.g. with the FLAG system, HA, etc. For studies of subcellular localization, fusion proteins with green fluorescent proteins (GFP) may be used. Such mutated genes may be used to study structure-function relationships of ASTH1 polypeptides, or to alter properties of the protein that affect its function or regulation. For example, constitutively active transcription factors, or a dominant negatively active protein that binds to the ASTH1 DNA target site without activating transcription, may be created in this manner.
Techniques for in vitro mutagenesis of cloned genes are known. Examples of protocols for scanning mutations may be found in Gustin et al., Biotechniques 14:22 (1993); Barany, Gene 37:111-23 (1985); Colicelli et al., Mol Gen Genet 199:537-9 (1985); and Prentki et al., Gene 29:303-13 (1984). Methods for site specific mutagenesis can be found in Sambrook et al., Molecular Cloning. A Laboratory Manual, CSH Press 1989, pp. 15.3-15.108; Weiner et al., Gene 126:35-41 (1993); Sayers et al., Biotechniques 13:592-6 (1992); Jones and Winistorfer, Biotechniques 12:528-30 (1992); Barton et al., Nucleic Acids Res 18:7349-55 (1990); Marotti and Tomich, Gene Anal Tech 6:67-70 (1989); and Zhu Anal Biochem 177:120-4 (1989).
Synthesis of ASTH1 Proteins
The subject gene may be employed for synthesis of a complete ASTH1 protein, or polypeptide fragments thereof, particularly fragments corresponding to functional domains; binding sites; etc.; and including fusions of the subject polypeptides to other proteins or parts thereof. For expression, an expression cassette may be employed, providing for a transcriptional and translational initiation region, which may be inducible or constitutive, where the coding region is operably linked under the transcriptional control of the transcriptional initiation region, and a transcriptional and translational termination region. Various transcriptional initiation regions may be employed that are functional in the expression host.
The polypeptides may be expressed in prokaryotes or eukaryotes in accordance with conventional ways, depending upon the purpose for expression. For large scale production of the protein, a unicellular organism, such as E. coli, B. subtilis, S. cerevisiae, or cells of a higher organism such as vertebrates, particularly mammals, e.g. COS 7 cells, may be used as the expression host cells. In many situations, it may be desirable to express the ASTH1 gene in mammalian cells, where the ASTH1 gene will benefit from native folding and post-translational modifications. Small peptides can also be synthesized in the laboratory.
With the availability of the polypeptides in large amounts, by employing an expression host, the polypeptides may be isolated and purified in accordance with conventional ways. A lysate may be prepared of the expression host and the lysate purified using HPLC, exclusion chromatography, gel electrophoresis, affinity chromatography, or other purification technique. The purified polypeptide will generally be at least about 80% pure, preferably at least about 90% pure, and may be up to and including 100% pure. Pure is intended to mean free of other proteins, as well as cellular debris.
The polypeptide is used for the production of antibodies, where short fragments provide for antibodies specific for the particular polypeptide, and larger fragments or the entire protein allow for the production of antibodies over the surface of the polypeptide. Antibodies may be raised to the wild-type or variant forms of ASTH1. Antibodies may be raised to isolated peptides corresponding to these domains, or to the native protein, e.g. by immunization with cells expressing ASTH1, immunization with liposomes having ASTH1 inserted in the membrane, etc.
Antibodies are prepared in accordance with conventional ways, where the expressed polypeptide or protein is used as an immunogen, by itself or conjugated to known immunogenic carriers, e.g. KLH, pre-S HBsAg, other viral or eukaryotic proteins, or the like. Various adjuvants may be employed, with a series of injections, as appropriate. For monoclonal antibodies, after one or more booster injections, the spleen is isolated, the lymphocytes immortalized by cell fusion, and then screened for high affinity antibody binding. The immortalized cells, i.e. hybridomas, producing the desired antibodies may then be expanded. For further description, see Monoclonal Antibodies: A Laboratory Manual, Harlow and Lane eds., Cold Spring Harbor Laboratories, Cold Spring Harbor, N.Y., 1988. If desired, the mRNA encoding the heavy and light chains may be isolated and mutagenized by cloning in E. coli, and the heavy and light chains mixed to further enhance the affinity of the antibody. Alternatives to in vivo immunization as a method of raising antibodies include binding to phage "display" libraries, usually in conjunction with in vitro affinity maturation.
Detection of ASTH1 Associated Asthma
Diagnosis of ASTH1 associated asthma is performed by protein, DNA or RNA sequence and/or hybridization analysis of any convenient sample from a patient, e.g. biopsy material, blood sample, scrapings from cheek, etc. A nucleic acid sample from a patient having asthma that may be associated with ASTH1, is analyzed for the presence of a predisposing polymorphism in ASTH1. A typical patient genotype will have at least one predisposing mutation on at least one chromosome. The presence of a polymorphic ASTH1 sequence that affects the activity or expression of the gene product, and confers an increased susceptibility to asthma is considered a predisposing polymorphism. Individuals are screened by analyzing their DNA or mRNA for the presence of a predisposing polymorphism, as compared to an asthma neutral sequence. Specific sequences of interest include any polymorphism that leads to clinical bronchial hyperreactivity or is otherwise associated with asthma, including, but not limited to, insertions, substitutions and deletions in the coding region sequence, intron sequences that affect splicing, or promoter or enhancer sequences that affect the activity and expression of the protein. Examples of specific ASTH1 polymorphisms in asthma patients are listed in Tables 3-8.
The CAAT box polymorphism of SEQ ID NO:12 and 13 (which is located within SEQ ID NO:14) is of particular interest. The "G" form, SEQ ID NO:13, can be associated with a propensity to develop bronchial hyperreactivity or asthma. Other polymorphisms in the surrounding region affect this association. It has been found that substitution of "G" for "A" results in decreased binding of nuclear proteins to the DNA motif.
The effect of an ASTH1 predisposing polymorphism may be modulated by the patient genotype in other genes related to asthma and atopy, including, but not limited to, the Fc.epsilon. receptor, Class I and Class II HLA antigens, T cell receptor and immunoglobulin genes, cytokines and cytokine receptors, and the like.
Screening may also be based on the functional or antigenic characteristics of the protein. Immunoassays designed to detect predisposing polymorphisms in ASTH1 proteins may be used in screening. Where many diverse mutations lead to a particular disease phenotype, functional protein assays have proven to be effective screening tools.
Biochemical studies may be performed to determine whether a candidate sequence polymorphism in the ASTH1 coding region or control regions is associated with disease. For example, a change in the promoter or enhancer sequence that affects expression of ASTH1 may result in predisposition to asthma. Expression levels of a candidate variant allele are compared to expression levels of the normal allele by various methods known in the art. Methods for determining promoter or enhancer strength include quantitation of the expressed natural protein; insertion of the variant control element into a vector with a reporter gene such as .beta.-galactosidase, luciferase, chloramphenicol acetyltransferase, etc. that provides for convenient quantitation; and the like. The activity of the encoded ASTH1 protein may be determined by comparison with the wild-type protein.
A number of methods are available for analyzing nucleic acids for the presence of a specific sequence. Where large amounts of DNA are available, genomic DNA is used directly. Alternatively, the region of interest is cloned into a suitable vector and grown in sufficient quantity for analysis. Cells that express ASTH1 genes, such as trachea cells, may be used as a source of mRNA, which may be assayed directly or reverse transcribed into cDNA for analysis. The nucleic acid may be amplified by conventional techniques, such as the polymerase chain reaction (PCR), to provide sufficient amounts for analysis. The use of the polymerase chain reaction is described in Saiki, et al. (1985) Science 239:487, and a review of current techniques may be found in Sambrook, et al. Molecular Cloning: A Laboratory Manual, CSH Press 1989, pp.14.2-14.33. Amplification may also be used to determine whether a polymorphism is present, by using a primer that is specific for the polymorphism. Alternatively, various methods are known in the art that utilize oligonucleotide ligation as a means of detecting polymorphisms, for examples see Riley et al. (1990) N.A.R. 18:2887-2890; and Delahunty et al. (1996) Am. J. Hum. Genet. 58:1239-1246.
A detectable label may be included in an amplification reaction. Suitable labels include fluorochromes, e.g. fluorescein isothiocyanate (FITC), rhodamine, Texas Red, phycoerythrin, allophycocyanin, 6-carboxyfluorescein (6-FAM), 2',7'-dimethoxy-4',5'-dichloro-6-carboxyfluorescein (JOE), 6-carboxy-X-rhodamine (ROX), 6-carboxy-2',4',7',4,7-hexachlorofluorescein (HEX), 5-carboxyfluorescein (5-FAM) or N,N,N',N'-tetramethyl-6-carboxyrhodamine (TAMRA), radioactive labels, e.g. .sup.32 P, 35S, .sup.3 H; etc. The label may be a two stage system, where the amplified DNA is conjugated to biotin, haptens, etc. having a high affinity binding partner, e.g. avidin, specific antibodies, etc., where the binding partner is conjugated to a detectable label. The label may be conjugated to one or both of the primers. Alternatively, the pool of nucleotides used in the amplification is labeled, so as to incorporate the label into the amplification product.
The sample nucleic acid, e.g. amplified or cloned fragment, is analyzed by one of a number of methods known in the art. The nucleic acid may be sequenced by dideoxy or other methods, and the sequence of bases compared to a neutral ASTH1 sequence. Hybridization with the variant sequence may also be used to determine its presence, by Southern blots, dot blots, etc. The hybridization pattern of a control and variant sequence to an array of oligonucleotide probes immobilised on a solid support, as described in U.S. Pat. No. 5,445,934, or in WO95/35505, may also be used as a means of detecting the presence of variant sequences. Single strand conformational polymorphism (SSCP) analysis, denaturing gradient gel electrophoresis (DGGE), mismatch cleavage detection, and heteroduplex analysis in gel matrices are used to detect conformational changes created by DNA sequence variation as alterations in electrophoretic mobility. Alternatively, where a polymorphism creates or destroys a recognition site for a restriction endonuclease (restriction fragment length polymorphism, RFLP), the sample is digested with that endonuclease, and the products size fractionated to determine whether the fragment was digested. Fractionation is performed by gel or capillary electrophoresis, particularly acrylamide or agarose gels.
The hybridization pattern of a control and variant sequence to an array of oligonucleotide probes immobilised on a solid support, as described in U.S. Pat. No. 5,445,934, or in WO95135505, may be used as a means of detecting the presence of variant sequences. In one embodiment of the invention, an array of oligonucleotides are provided, where discrete positions on the array are complementary to at least a portion of mRNA or genomic DNA of the ASTH1 locus. Such an array may comprise a series of oligonucleotides, each of which can specifically hybridize to a nucleic acid, e.g. mRNA, cDNA, genomic DNA, etc. from the ASTH1 locus.
An array may include all or a subset of the polymorphisms listed in Table 3 (SEQ ID NOs:16-126). One or both polymorphic forms may be present in the array, for example the polymorphism of SEQ ID NO:12 and 13 may be represented by either, or both, of the listed sequences. Usually such an array will include at least 2 different polymorphic sequences, i.e. polymorphisms located at unique positions within the locus, usually at least about 5, more usually at least about 10, and may include as many as 50 to 100 different polymorphisms. The oligonucleotide sequence on the array will usually be at least about 12 nt in length, may be the length of the provided polymorphic sequences, or may extend into the flanking regions to generate fragments of 100 to 200 nt in length. For examples of arrays, see Hacia et al. (1996) Nature Genetics 14:441-447; Lockhart et al. (1996) Nature Biotechnol. 14:1675-1680; and De Risi et al. (1996) Nature Genetics 14:457-460.
Antibodies specific for ASTH1 polymorphisms may be used in screening immunoassays. A reduction or increase in neutral ASTH1 and/or presence of asthma associated polymorphisms is indicative that asthma is ASTH1-associated. A sample is taken from a patient suspected of having ASTH1-associated asthma. Samples, as used herein, include biological fluids such as tracheal lavage, blood, cerebrospinal fluid, tears, saliva, lymph, dialysis fluid and the like; organ or tissue culture derived fluids; and fluids extracted from physiological tissues. Also included in the term are derivatives and fractions of such fluids. Biopsy samples are of particular interest, e.g. trachea scrapings, etc. The number of cells in a sample will generally be at least about 101, usually at least 104 more usually at least about 10.sup.5. The cells may be dissociated, in the case of solid tissues, or tissue sections may be analyzed. Alternatively a lysate of the cells may be prepared.
Diagnosis may be performed by a number of methods. The different methods all determine the absence or presence or altered amounts of normal or abnormal ASTH1 in patient cells suspected of having a predisposing polymorphism in ASTH1. For example, detection may utilize staining of cells or histological sections, performed in accordance with conventional methods. The antibodies of interest are added to the cell sample, and incubated for a period of time sufficient to allow binding to the epitope, usually at least about 10 minutes. The antibody may be labeled with radioisotopes, enzymes, fluorescers, chemiluminescers, or other labels for direct detection. Alternatively, a second stage antibody or reagent is used to amplify the signal. Such reagents are well known in the art. For example, the primary antibody may be conjugated to biotin, with horseradish peroxidase-conjugated avidin added as a second stage reagent. Final detection uses a substrate that undergoes a color change in the presence of the peroxidase. The absence or presence of antibody binding may be determined by various methods, including flow cytometry of dissociated cells, microscopy, radiography, scintillation counting, etc.
An alternative method for diagnosis depends on the in vitro detection of binding between antibodies and ASTH1 in a lysate. Measuring the concentration of ASTH1 binding in a sample or fraction thereof may be accomplished by a variety of specific assays. A conventional sandwich type assay may be used. For example, a sandwich assay may first attach ASTH1-specific antibodies to an insoluble surface or support. The particular manner of binding is not crucial so long as it is compatible with the reagents and overall methods of the invention. They may be bound to the plates covalently or non-covalently, preferably non-covalently.
The insoluble supports may be any compositions to which polypeptides can be bound, which is readily separated from soluble material, and which is otherwise compatible with the overall method. The surface of such supports may be solid or porous and of any convenient shape. Examples of suitable insoluble supports to which the receptor is bound include beads, e.g. magnetic beads, membranes and microtiter plates. These are typically made of glass, plastic (e.g. polystyrene), polysaccharides, nylon or nitrocellulose. Microtiter plates are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples.
Patient sample lysates are then added to separately assayable supports (for example, separate wells of a microtiter plate) containing antibodies. Preferably, a series of standards, containing known concentrations of normal and/or abnormal ASTH1 is assayed in parallel with the samples or aliquots thereof to serve as controls. Preferably, each sample and standard will be added to multiple wells so that mean values can be obtained for each. The incubation time should be sufficient for binding, generally, from about 0.1 to 3 hr is sufficient. After incubation, the insoluble support is generally washed of non-bound components. Generally, a dilute non-ionic detergent medium at an appropriate pH, generally 7-8, is used as a wash medium. From one to six washes may be employed, with sufficient volume to thoroughly wash non-specifically bound proteins present in the sample.
After washing, a solution containing a second antibody is applied. The antibody will bind ASTH1 with sufficient specificity such that it can be distinguished from other components present. The second antibodies may be labeled to facilitate direct, or indirect quantification of binding. Examples of labels that permit direct measurement of second receptor binding include radiolabels, such as .sup.3 H or .sup.125 I, fluorescers, dyes, beads, chemilumninescers, colloidal particles, and the like. Examples of labels which permit indirect measurement of binding include enzymes where the substrate may provide for a colored or fluorescent product. In a preferred embodiment, the antibodies are labeled with a covalently bound enzyme capable of providing a detectable product signal after addition of suitable substrate. Examples of suitable enzymes for use in conjugates include horseradish peroxidase, alkaline phosphatase, malate dehydrogenase and the like. Where not commercially available, such antibody-enzyme conjugates are readily produced by techniques known to those skilled in the art. The incubation time should be sufficient for the labeled ligand to bind available molecules. Generally, from about 0.1 to 3 hr is sufficient, usually 1 hr sufficing.
After the second binding step, the insoluble support is again washed free of non-specifically bound material. The signal produced by the bound conjugate is detected by conventional means. Where an enzyme conjugate is used, an appropriate enzyme substrate is provided so a detectable product is formed.
Other immunoassays are known in the art and may find use as diagnostics. Ouchterlony plates provide a simple determination of antibody binding. Western blots may be performed on protein gels or protein spots on filters, using a detection system specific for ASTH1 as desired, conveniently using a labeling method as described for the sandwich assay.
Other diagnostic assays of interest are based on the functional properties of ASTH1 proteins. Such assays are particularly useful where a large number of different sequence changes lead to a common phenotype, ie. altered protein function leading to bronchial hyperreactivity. For example, a functional assay may be based on the transcriptional changes mediated by ASTH1 gene products. Other assays may, for example, detect conformational changes, size changes resulting from insertions, deletions or truncations, or changes in the subcellular localization of ASTH1 proteins.
In a protein truncation test, PCR fragments amplified from the ASTH1 gene or its transcript are used as templates for in vivo transcription/translation reactions to generate protein products. Separation by gel electrophoresis is performed to determine whether the polymorphic gene encodes a truncated protein, where truncations may be associated with a loss of function.
Diagnostic screening may also be performed for polymorphisms that are genetically linked to a predisposition for bronchial hyperreactivity, particularly through the use of microsatellite markers or single nucleotide polymorphisms. Frequently the microsatellite polymorphism itself is not phenotypically expressed, but is linked to sequences that result in a disease predisposition. However, in some cases the microsatellite sequence itself may affect gene expression. Microsatellite linkage analysis may be performed alone, or in combination with direct detection of polymorphisms, as described above. The use of microsatellite markers for genotyping is well documented. For examples, see Mansfield et al. (1994) Genomics 24:225-233; Ziegle et al. (1992) Genomics 14:1026-1031; Dib et al., supra.
Microsatellite loci that are useful in the subject methods have the general formula:
U(R).sub.n U',
where U and U' are non-repetitive flanking sequences that uniquely identify the particular locus, R is a repeat motif, and n is the number of repeats. The repeat motif is at least 2 nucleotides in length, up to 7, usually 2-4 nucleotides in length. Repeats can be simple or complex. The flanking sequences U and U' uniquely identify the microsatellite locus within the human genome. U and U' are at least about 18 nucleotides in length, and may extend several hundred bases up to about 1 kb on either side of the repeat. Within U and U', sequences are selected for amplification primers. The exact composition of the primer sequences are not critical to the invention, but they must hybridize to the flanking sequences U and U', respectively, under stringent conditions. Criteria for selection of amplification primers are as previously discussed. To maximize the resolution of size differences at the locus, it is preferable to chose a primer sequence that is close to the repeat sequence, such that the total amplification product is between 100-500 nucleotides in length.
The number of repeats at a specific locus, n, is polymorphic in a population, thereby generating individual differences in the length of DNA that lies between the amplification primers. The number will vary from at least 1 repeat to as many as about 100 repeats or more.
The primers are used to amplify the region of genomic DNA that contains the repeats. Conveniently, a detectable label will be included in the amplification reaction, as previously described. Multiplex amplification may be performed in which several sets of primers are combined in the same reaction tube. This is particularly advantageous when limited amounts of sample DNA are available for analysis. Conveniently, each of the sets of primers is labeled with a different fluorochrome.
After amplification, the products are size fractionated. Fractionation may be performed by gel electrophoresis, particularly denaturing acrylamide or agarose gels. A convenient system uses denaturing polyacrylamide gels in combination with an automated DNA sequencer, see Hunkapillar et al. (1991) Science 254:59-74. The automated sequencer is particularly useful with multiplex amplification or pooled products of separate PCR reactions. Capillary electrophoresis may also be used for fractionation. A review of capillary electrophoresis may be found in Landers, et al. (1993) BioTechniques 14:98-111. The size of the amplification product is proportional to the number of repeats (n) that are present at the locus specified by the primers. The size will be polymorphic in the population, and is therefore an allelic marker for that locus.
A number of markers in the region of the ASTH1 locus have been identified, and are listed in Table 1 in the Experimental section (SEQ ID NOs:160-273). Of particular interest for diagnostic purposes is the marker D11S2008, in which individuals having alleles C or F at this locus, particularly in combination with the CAAT box polymorphism and other polymorphisms, are predisposed to develop bronchial hyperreactivity or asthma. The association of D11 S2008 alleles is as follows:
______________________________________ Number of TATC repeats Association relative to allele CAllele with asthma (SEQ ID NO:15)______________________________________A no -2B no -1C yes equivalentD no +1E no +2F yes +3G no +4H no +5______________________________________
A DNA sequence of interest for diagnosis comprises the D11S2008 primer sequences shown in Table 1 (SEQ ID NO:242 and 243), flanking one or three repeats of SEQ ID NO-15.
Other microsatellite markers of interest for diagnostic purposes are CA39.sub.-- 2; 774F; 774J; 774O; L19PENTA1; 65P14TE1; AFM205YG5; D11S907; D11S4200; 774N; CA11-11; 774L; AFM283WH9; ASMI14 and D11S1900 (primer sequences are provided in Table 1, the repeats are provided in Table 1 B).
Regulation of ASTH1 Expression
The ASTH1 genes are useful for analysis of ASTH1 expression, e.g. in determining developmental and tissue specific patterns of expression, and for modulating expression in vitro and in vivo. The regulatory region of SEQ ID NO:1 may also be used to investigate analysis of ASTH1 expression. Vectors useful for introduction of the gene include plasmids and viral vectors. Of particular interest are retroviral-based vectors, e.g. Moloney murine leukemia virus and modified human immunodeficiency virus; adenovirus vectors, etc. that are maintained transiently or stably in mammalian cells. A wide variety of vectors can be employed for transfection and/or integration of the gene into the genome of the cells. Alternatively, micro-injection may be employed, fusion, or the like for introduction of genes into a suitable host cell. See, for example, Dhawan et al. (1991) Science 254:1509-1512 and Smith et al. (1990) Molecular and Cellular Biology 3268-3271.
Administration of vectors to the lungs is of particular interest. Frequently such methods utilize liposomal formulations, as described in Eastman et al. (1997) Hum Gene Ther 8:765-773; Oudrhiri et al. (1997) P.N.A.S. 94:1651-1656; McDonald et al. (1997) Hum Gene Ther 8:411-422.
The expression vector will have a transcriptional initiation region oriented to produce functional mRNA. The native transcriptional initiation region, e.g. SEQ ID NO:14, or an exogenous transcriptional initiation region may be employed. The promoter may be introduced by recombinant methods in vitro, or as the result of homologous integration of the sequence into a chromosome. Many strong promoters are known in the art, including the .beta.-actin promoter, SV40 early and late promoters, human cytomegalovirus promoter, retroviral LTRs, methallothionein responsive element (MRE), tetracycline-inducible promoter constructs, etc.
Expression vectors generally have convenient restriction sites located near the promoter sequence to provide for the insertion of nucleic acid sequences. Transcription cassettes may be prepared comprising a transcription initiation region, the target gene or fragment thereof, and a transcriptional termination region. The transcription cassettes may be introduced into a variety of vectors, e.g. plasmid; retrovirus, e.g. lentivirus; adenovirus; and the like, where the vectors are able to transiently or stably be maintained in the cells, usually for a period of at least about one day, more usually for a period of at least about several days to several weeks.
Antisense molecules are used to down-regulate expression of ASTH1 in cells. The anti-sense reagent may be antisense oligonucleotides (ODN), particularly synthetic ODN having chemical modifications from native nucleic acids, or nucleic acid constructs that express such anti-sense molecules as RNA. The antisense sequence is complementary to the mRNA of the targeted gene, and inhibits expression of the targeted gene products. Antisense molecules inhibit gene expression through various mechanisms, e.g. by reducing the amount of mRNA available for translation, through activation of RNAse H, or steric hindrance. One or a combination of antisense molecules may be administered, where a combination may comprise multiple different sequences.
Antisense molecules may be produced by expression of all or a part of the target gene sequence in an appropriate vector, where the transcriptional initiation is oriented such that an antisense strand is produced as an RNA molecule. Alternatively, the antisense molecule is a synthetic oligonucleotide. Antisense oligonucleotides will generally be at least about 7, usually at least about 12, more usually at least about 20 nucleotides in length, and not more than about 500, usually not more than about 50, more usually not more than about 35 nucleotides in length, where the length is governed by efficiency of inhibition, specificity, including absence of cross-reactivity, and the like. It has been found that short oligonucleotides, of from 7 to 8 bases in length, can be strong and selective inhibitors of gene expression (see Wagner et al. (1996) Nature Biotechnoloay 14:840-844).
A specific region or regions of the endogenous sense strand mRNA sequence is chosen to be complemented by the antisense sequence. Selection of a specific sequence for the oligonucleotide may use an empirical method, where several candidate sequences are assayed for inhibition of expression of the target gene in an in vitro or animal model. A combination of sequences may also be used, where several regions of the mRNA sequence are selected for antisense complementation.
Antisense oligonucleotides may be chemically synthesized by methods known in the art (see Wagner et al. (1993) supra. and Milligan et al., supra.) Preferred oligonucleotides are chemically modified from the native phosphodiester structure, in order to increase their intracellular stability and binding affinity. A number of such modifications have been described in the literature, which alter the chemistry of the backbone, sugars or heterocyclic bases.
Among useful changes in the backbone chemistry are phosphorothioates; phosphorodithioates, where both of the non-bridging oxygens are substituted with sulfur; phosphoroamidites; alkyl phosphotriesters and boranophosphates. Achiral phosphate derivatives include 3'-0'-5'-S-phosphorothioate, 3'-S-5'-0-phosphorothioate, 3'-CH2-5'-0-phosphonate and 3'-NH-5'-0-phosphoroamidate. Peptide nucleic acids replace the entire ribose phosphodiester backbone with a peptide linkage. Sugar modifications are also used to enhance stability and affinity. The .alpha.-anomer of deoxyribose may be used, where the base is inverted with respect to the natural .beta.-anomer. The 2'-OH of the ribose sugar may be altered to form 2'-O-methyl or 2'-O-allyl sugars, which provides resistance to degradation without comprising affinity. Modification of the heterocyclic bases must maintain proper base pairing. Some useful substitutions include deoxyuridine for deoxythymidine; 5-methyl-2'-deoxycytidine and 5-bromo-2'-deoxycytidine for deoxycytidine. 5-propynyl-2'-deoxyuridine and 5-propynyl-2'-deoxycytidine have been shown to increase affinity and biological activity when substituted for deoxythymidine and deoxycytidine, respectively.
As an alternative to anti-sense inhibitors, catalytic nucleic acid compounds, e.g. ribozymes, anti-sense conjugates, etc. may be used to inhibit gene expression. Ribozymes may be synthesized in vitro and administered to the patient, or may be encoded on an expression vector, from which the ribozyme is synthesized in the targeted cell (for example, see International patent application WO 9523225, and Beigelman et al. (1995) Nucl. Acids Res 23:4434-42). Examples of oligonucleotides with catalytic activity are described in WO 9506764. Conjugates of anti-sense ODN with a metal complex, e.g. terpyridylCu(II), capable of mediating mRNA hydrolysis are described in Bashkin et al. (1995) Appl Biochem Biotechnol 54:43-56.
Therapeutic Use of ASTH1 Protein
A host may be treated with intact ASTH1 protein, or an active fragment thereof to modulate or reduce bronchial hypereactivity. Desirably, the peptides will not induce an immune response, particularly an antibody response. Xenogeneic analogs may be screened for their ability to provide a therapeutic effect without raising an immune response. The protein or peptides may also be administered to in vitro cell cultures.
Various methods for administration may be employed. The polypeptide formulation may be given orally, or may be injected intravascularly, subcutaneously, peritoneally, etc. Methods of administration by inhalation are well-known in the art. The dosage of the therapeutic formulation will vary widely, depending upon the nature of the disease, the frequency of administration, the manner of administration, the clearance of the agent from the host, and the like. The initial dose may be larger, followed by smaller maintenance doses. The dose may be administered as infrequently as weekly or biweekly, or fractionated into smaller doses and administered daily, semi-weekly, etc. to maintain an effective dosage level. In many cases, oral administration will require a higher dose than if administered intravenously. The amide bonds, as well as the amino and carboxy termini, may be modified for greater stability on oral administration.
The subject peptides may be prepared as formulations at a pharmacologically effective dose in pharmaceutically acceptable media, for example normal saline, PBS, etc. The additives may include bactericidal agents, stabilizers, buffers, or the like. In order to enhance the half-life of the subject peptide or subject peptide conjugates, the peptides may be encapsulated, introduced into the lumen of liposomes, prepared as a colloid, or another conventional technique may be employed that provides for an extended lifetime of the peptides.
The peptides may be administered as a combination therapy with other pharmacologically active agents. The additional drugs may be administered separately or in conjunction with the peptide compositions, and may be included in the same formulation.
Models for Asthma
The subject nucleic acids can be used to generate genetically modified non-human animals or site specific gene modifications in cell lines. The term "transgenic" is intended to encompass genetically modified animals having a deletion or other knock-out of ASTH1 gene activity, having an exogenous ASTH1 gene that is stably transmitted in the host cells, or having an exogenous ASTH1 promoter operably linked to a reporter gene. Transgenic animals may be made through homologous recombination, where the ASTH1 locus is altered. Alternatively, a nucleic acid construct is randomly integrated into the genome. Vectors for stable integration include plasmids, retroviruses and other animal viruses, YACs, and the like. Of interest are transgenic mammals, e.g. cows, pigs, goats, horses, etc., and particularly rodents, e.g. rats, mice, etc.
A "knock-out" animal is genetically manipulated to substantially reduce, or eliminate endogenous ASTH1 function. Different approaches may be used to achieve the "knock-out". A chromosomal deletion of all or part of the native ASTH1 homolog may be induced. Deletions of the non-coding regions, particularly the promoter region, 3' regulatory sequences, enhancers, or deletions of gene that activate expression of ASTH1 genes. A functional knock-out may also be achieved by the introduction of an anti-sense construct that blocks expression of the native ASTH1 genes (for example, see Li and Cohen (1996) Cell 85:319-329).
Transgenic animals may be made having exogenous ASTH1 genes. The exogenous gene is usually either from a different species than the animal host, or is otherwise altered in its coding or non-coding sequence. The introduced gene may be a wild-type gene, naturally occurring polymorphism, or a genetically manipulated sequence, for example those previously described with deletions, substitutions or insertions in the coding or non-coding regions. The introduced sequence may encode an ASTH1 polypeptide, or may utilize the ASTH1 promoter operably linked to a reporter gene. Where the introduced gene is a coding sequence, it usually operably linked to a promoter, which may be constitutive or inducible, and other regulatory sequences required for expression in the host animal.
Specific constructs of interest, but are not limited to, include anti-sense ASTH1, which will block ASTH1 expression, expression of dominant negative ASTH1 mutations, and over-expression of a ASTH1 gene. A detectable marker, such as lac Z may be introduced into the ASTH1 locus, where upregulation of ASTH1 expression will result in an easily detected change in phenotype. Constructs utilizing the ASTH1 promoter region, e.g. SEQ ID NO:1; SEQ ID NO:14, in combination with a reporter gene or with the coding region of ASTH1J or ASTH1I are also of interest.
The modified cells or animals are useful in the study of ASTH1 function and regulation. Animals may be used in functional studies, drug screening, etc., e.g. to determine the effect of a candidate drug on asthma. A series of small deletions and/or substitutions may be made in the ASTH1 gene to determine the role of different exons in DNA binding, transcriptional regulation, etc. By providing expression of ASTH1 protein in cells in which it is otherwise not normally produced, one can induce changes in cell behavior. These animals are also useful for exploring models of inheritance of asthma, e.g. dominant v. recessive; relative effects of different alleles and synergistic effects between ASTH1I and ASTH1J and other asthma genes elsewhere in the genome.
DNA constructs for homologous recombination will comprise at least a portion of the ASTH1 gene with the desired genetic modification, and will include regions of homology to the target locus. DNA constructs for random integration need not include regions of homology to mediate recombination. Conveniently, markers for positive and negative selection are included. Methods for generating cells having targeted gene modifications through homologous recombination are known in the art. For various techniques for transfecting mammalian cells, see Keown et al. (1990) Methods in Enzymology 185:527-537.
For embryonic stem (ES) cells, an ES cell line may be employed, or embryonic cells may be obtained freshly from a host, e.g. mouse, rat, guinea pig, etc. Such cells are grown on an appropriate fibroblast-feeder layer or grown in the presence of appropriate growth factors, such as leukemia inhibiting factor (LIF). When ES cells have been transformed, they may be used to produce transgenic animals. After transformation, the cells are plated onto a feeder layer in an appropriate medium. Cells containing the construct may be detected by employing a selective medium. After sufficient time for colonies to grow, they are picked and analyzed for the occurrence of homologous recombination or integration of the construct. Those colonies that are positive may then be used for embryo manipulation and blastocyst injection. Blastocysts are obtained from 4 to 6 week old superovulated females. The ES cells are trypsinized, and the modified cells are injected into the blastocoel of the blastocyst. After injection, the blastocysts are returned to each uterine horn of pseudopregnant females. Females are then allowed to go to term and the resulting litters screened for mutant cells having the construct. By providing for a different phenotype of the blastocyst and the ES cells, chimeric progeny can be readily detected.
The chimeric animals are screened for the presence of the modified gene and males and females having the modification are mated to produce homozygous progeny. If the gene alterations cause lethality at some point in development, tissues or organs can be maintained as allogeneic or congenic grafts or transplants, or in in vitro culture.
Investigation of genetic function may utilize non-mammalian models, particularly using those organisms that are biologically and genetically well-characterized, such as C. elegans, D. melanogaster and S. cerevisiae. For example, transposon (Tcl) insertions in the nematode homolog of an ASTH1 gene or promoter region may be made. The subject gene sequences may be used to knock-out or to complement defined genetic lesions in order to determine the physiological and biochemical pathways involved in ASTH1 function. A number of human genes have been shown to complement mutations in lower eukaryotes.
Drug screening may be performed in combination with the subject animal models. Many mammalian genes have homologs in yeast and lower animals. The study of such homologs' physiological role and interactions with other proteins can facilitate understanding of biological function. In addition to model systems based on genetic complementation, yeast has been shown to be a powerful tool for studying protein-protein interactions through the two hybrid system described in Chien et al. (1991) P.N.A.S. 88:9578-9582. Two-hybrid system analysis is of particular interest for exploring transcriptional activation by ASTH1 proteins.
Drug Screening Assays
By providing for the production of large amounts of ASTH1 protein, one can identify ligands or substrates that bind to, modulate or mimic the action of ASTH1. Areas of investigation are the development of asthma treatments. Drug screening identifies agents that provide a replacement or enhancement for ASTH1 function in affected cells. Conversely, agents that reverse or inhibit ASTH1 function may stimulate bronchial reactivity. Of particular interest are screening assays for agents that have a low toxicity for human cells. A wide variety of assays may be used for this purpose, including labeled in vitro protein-protein binding assays, protein-DNA binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, and the like. The purified protein may also be used for determination of three-dimensional crystal structure, which can be used for modeling intermolecular interactions, transcriptional regulation, etc.
The term "agent" as used herein describes any molecule, e.g. protein or pharmaceutical, with the capability of altering or mimicking the physiological function of ASTH1. Generally a plurality of assay mixtures are run in parallel with different agent concentrations to obtain a differential response to the various concentrations. Typically, one of these concentrations serves as a negative control, i.e. at zero concentration or below the level of detection.
Candidate agents encompass numerous chemical classes, though typically they are organic molecules, preferably small organic compounds having a molecular weight of more than 50 and less than about 2,500 daltons. Candidate agents comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Candidate agents are also found among biomolecules including, but not limited to: peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof.
Candidate agents are obtained from a wide variety of sources including libraries of synthetic or natural compounds. For example, numerous means are available for random and directed synthesis of a wide variety of organic compounds and biomolecules, including expression of randomized oligonucleotides and oligopeptides. Alternatively, libraries of natural compounds in the form of bacterial, fungal, plant and animal extracts are available or readily produced. Additionally, natural or synthetically produced libraries and compounds are readily modified through conventional chemical, physical and biochemical means, and may be used to produce combinatorial libraries. Known pharmacological agents may be subjected to directed or random chemical modifications, such as acylation, alkylation, esterification, amidification, etc. to produce structural analogs.
Where the screening assay is a binding assay, one or more of the molecules may be joined to a label, where the label can directly or indirectly provide a detectable signal. Various labels include radioisotopes, fluorescers, chemiluminescers, enzymes, specific binding molecules, particles, e.g. magnetic particles, and the like. Specific binding molecules include pairs, such as biotin and streptavidin, digoxin and antidigoxin etc. For the specific binding members, the complementary member would normally be labeled with a molecule that provides for detection, in accordance with known procedures.
A variety of other reagents may be included in the screening assay. These include reagents like salts, neutral proteins, e.g. albumin, detergents, etc that are used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions. Reagents that improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc. may be used. The mixture of components are added in any order that provides for the requisite binding. Incubations are performed at any suitable temperature, typically between 4 and 40.degree. C. Incubation periods are selected for optimum activity, but may also be optimized to facilitate rapid high-throughput screening. Typically between 0.1 and 1 hours will be sufficient.
Other assays of interest detect agents that mimic ASTH1 function. For example, candidate agents are added to a cell that lacks functional ASTH1, and screened for the ability to reproduce ASTH1 in a functional assay.
The compounds having the desired pharmacological activity may be administered in a physiologically acceptable carrier to a host for treatment of asthma attributable to a defect in ASTH1 function. The compounds may also be used to enhance ASTH1 function. The therapeutic agents may be administered in a variety of ways, orally, topically, parenterally e.g. subcutaneously, intraperitoneally, by viral infection, intravascularly, etc. Inhaled treatments are of particular interest. Depending upon the manner of introduction, the compounds may be formulated in a variety of ways. The concentration of therapeutically active compound in the formulation may vary from about 0.1-100 wt. %.
The pharmaceutical compositions can be prepared in various forms, such as granules, tablets, pills, suppositories, capsules, suspensions, salves, lotions and the like. Pharmaceutical grade organic or inorganic carriers and/or diluents suitable for oral and topical use can be used to make up compositions containing the therapeutically-active compounds. Diluents known to the art include aqueous media, vegetable and animal oils and fats. Stabilizing agents, wetting and emulsifying agents, salts for varying the osmotic pressure or buffers for securing an adequate pH value, and skin penetration enhancers can be used as auxiliary agents.
Pharmacogenetics
Pharmacogenetics is the linkage between an individual's genotype and that individual's ability to metabolize or react to a therapeutic agent. Differences in metabolism or target sensitivity can lead to severe toxicity or therapeutic failure by altering the relation between bioactive dose and blood concentration of the drug. In the past few years, numerous studies have established good relationships between polymorphisms in metabolic enzymes or drug targets, and both response and toxicity. These relationships can be used to individualize therapeutic dose administration.
Genotyping of polymorphic alleles is used to evaluate whether an individual will respond well to a particular therapeutic regimen. The polymorphic sequences are also used in drug screening assays, to determine the dose and specificity of a candidate therapeutic agent. A candidate ASTH1 polymorphism is screened with a target therapy to determine whether there is an influence on the effectiveness in treating asthma. Drug screening assays are performed as described above. Typically two or more different sequence polymorphisms are tested for response to a therapy.
Drugs currently used to treat asthma include beta 2-agonists, glucocorticoids, theophylline, cromones, and anticholinergic agents. For acute, severe asthma, the inhaled beta 2-agonists are the most effective bronchodilators. Short-acting forms give rapid relief; long-acting agents provide sustained relief and help nocturnal asthma. First-line therapy for chronic asthma is inhaled glucocorticoids, the only currently available agents that reduce airway inflammation. Theophylline is a bronchodilator that is useful for severe and nocturnal asthma, but recent studies suggest that it may also have an immunomodulatory effect. Cromones work best for patients who have mild asthma: they have few adverse effects, but their activity is brief, so they must be given frequently. Cysteinil leukotrienes are important mediators of asthma, and inhibition of their effects may represent a potential breakthrough in the therapy of allergic rhinitis and asthma.
Where a particular sequence polymorphism correlates with differential drug effectiveness, diagnostic screening may be performed. Diagnostic methods have been described in detail in a preceding section. The presence of a particular polymorphism is detected, and used to develop an effective therapeutic strategy for the affected individual.
EXPERIMENTAL
The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the subject invention, and are not intended to limit the scope of what is regarded as the invention. Efforts have been made to ensure accuracy with respect to the numbers used (e.g. amounts, temperature, concentrations, etc.) but some experimental errors and deviations should be allowed for. Unless otherwise indicated, parts are parts by weight, molecular weight is average molecular weight, temperature is in degrees centigrade; and pressure is at or near atmospheric.
Materials and Methods
Asthma families for genetic mapping studies
Asthma phenotype measurements and blood samples were obtained from the inhabitants of Tristan da Cunha, an isolated island in the South Atlantic, and from asthma families in Toronto, Canada (see Zamel et al., (1996) supra.) The 282 inhabitants of Tristan da Cunha form a single large extended family descended from 28 original founders. Settlement of Tristan da Cunha occurred beginning in 1817 with soldiers who remained behind when a British garrison was withdrawn from the island, followed by the survivors of several shipwrecks. In 1827 five women from St. Helena, one with children, emigrated to Tristan da Cunha and married island men. One of these women is said to have been asthmatic, and could be the origin of a genetic founder effect for asthma in this population. Inbreeding has resulted in kinship resemblances of at least first cousin levels for all individuals.
The Tristan da Cunha family pedigrees were ascertained through review of baptismal, marriage and medical records, as well as reliably accurate historical records of the early inhabitants (Zamel (1995) Can. Respir. J. 2:18). The prevalence of asthma on Tristan da Cunha is high; 23% had a definitive diagnosis of asthma.
The Toronto cohort included 59 small families having at least one affected individual. These were ascertained based on the following criteria: (i) an affected proband; (ii) availability of at least one sibling of the proband, either affected or unaffected; (iii) at least one living parent from whom DNA could be obtained. A set of 156 "triad" families consisting of an affected proband and his or her parents were also collected. Signed consent forms were obtained from each individual prior to commencement of phenotyping and blood sample collection. The Toronto patients were mainly of mixed European ancestry.
Clinical characterization
A standardized questionnaire based on that of the American Thoracic Society (American Lung Association recommended respiratory diseases questionnaire for use with adults and children in epidemiology research. 1978. American Review of Respiratory Disease 118(2):7-53) was used to record the presence of respiratory symptoms such as cough, sputum and wheezing; the presence of other chest disorders including recent upper respiratory tract infection, allergic history; asthmatic attacks including onset, offset, confirmation by a physician, prevalence, severity and precipitating factors; other illnesses and smoking history; and all medications used within the previous 3 months. A physician-confirmed asthmatic attack was the principal criterion for a diagnosis of asthma.
Skin atopy was determined by skin prick tests to common allergens: A. fumigatus, Cladosporium, Alternaia, egg, milk, wheat, tree, dog, grass, horse, house dust, cat, feathers, house dust mite D. fadnae, and house dust mite D. pteronyssinus. Atopy testing of Toronto subjects omitted D. pteronyssinus and added cockroach and ragweed allergens. Saline and histamine controls were also performed (Bencard Laboratories, Mississauga, Ontario). Antihistamines were withdrawn for at least 48 hours prior to testing. Wheal diameters were corrected by subtraction of the saline control wheal diameter, and a corrected wheal size of >3 mm recorded 10 min after application was considered a positive response.
Airway responsiveness was assessed by a methacholine challenge test in those subjects with a baseline FEV1 (forced exhalation volume in one second) >70% of predicted (Crapo et al. (1981) Am. Rev. Respir. Dis. 123:659). Methacholine challenge response was determined using the tidal breathing method (Cockcroft et al. (1977) Clin. Allergy 7:235). Doubling doses of methacholine from 0.03 to 16 mg/ml were administered using a Wright nebulizer at 4-min intervals to measure the provocative concentration of methacholine producing a 20% fall in FEV1 (PC20). If FEV1 was <70% of predicted, a bronchodilator response to 400 mg salbutamol aerosol was used to determine airway responsiveness. Both methacholine challenges and bronchodilator responses were measured using a computerized bronchial challenge system (S&M Instrument Co. Inc., Doyleston, Pa.) consisting of a software package and interface board installed in a Toshiba T1850C laptop computer and connected to a flow sensor (RS232FS). The power source for instruments used on Tristan da Cunha has been described (Zamel et al. (1996) supra.) Increased airway responsiveness was defined as a PC20<4.0 mg/ml or a >15% improvement in FEV1 15 min postbronchodilator. Participants were asked to withhold bronchodilators at least 8 h before testing; inhaled or systemic steroids were maintained at the usual dosage. Subjects with a history of an upper respiratory tract infection within a month of testing were rechallenged at a later date.
Genotyping
PCR primer pairs were synthesized using Applied Biosystems 394 automated oligo synthesizer. The forward primer of each pair was labeled with either FAM, HEX, or TET phosphoramidites (Applied Biosystems). No oligo purification step was performed.
Genomic DNA was extracted from whole blood. PCR was performed using PTC100 thermocyclers (MJ Research). Reactions contained 10 mM Tris-HCl, pH 8.3; 1.5-3.0 mM MgCl.sub.2 ; 50 mM KCl; 0.01% gelatin; 250 .mu.M each dGTP, dATP, dTTP, dCTP; 20 .mu.M each PCR primer; 20 ng genomic DNA; and 0.75 U Taq Polymerase (Perkin Elmer Cetus) in a final volume of 20 .mu.l. Reactions were performed in 96 well polypropylene microtiter plates (Robbins Scientific) with an initial 94.degree. C., 3 min. denaturation followed by 35 cycles of 30 sec. at 94.degree. C., 30 sec. at the annealing temp., and 30 sec. at 72.degree. C., with a final 2 min. extension at 72.degree. C. following the last cycle. Dye label, annealing temperature, and final magnesium concentration were specific to the individual marker.
Dye label intensity and quantity of PCR product (as assessed on agarose gels) were used to determine the amount to be pooled for each marker locus. The pooled products were precipitated and the product pellets mixed with 0.4 .mu.l Genescan 500 Tamra size standard, 2 .mu.l formamide, and 1 .mu.l ABI loading dye. Plates of PCR product pools were heated to 80.degree. C. for 5 minutes and immediately placed on ice prior to gel loading.
PCR products were electrophoresed on denaturing 6% polyacrylamide gels at a constant 1000 volts using ABI 373a instruments. Peak detection, sizing, and stutter band filtering were achieved using Genescan 1.2 and Genotyper 1.1 software (Applied Biosystems). Genotype data were subsequently submitted to quality control and consistency checks (Hall et al. (1996) Genome Res. 6:781).
Genotyping of `saturation` markers in the ASTH1 region was done by the method described above with several exceptions. In most cases, the unlabeled primer of each pair was modified with the sequence GTTTCTT at the 5' end (Smith et al. 1995 Genome Res. 5:312). Amplitaq Gold (Perkin Elmer Cetus) and buffer D (2.5 mM MgCl.sub.2, 33.5 mM Tris-HCl pH 8.0, 8.3 mM (NH.sub.4).sub.2 SO.sub.4, 25 mM KCl, 85 .mu.g/ml BSA) were used in the PCR. A `touchdown` amplification profile was employed in which the annealing temperature began at 66.degree. C. and decreased one degree per cycle to a final 20 cycles at 56.degree. C. Products were run on 4.25% polyacrylamide gels using ABI 377 instruments. The data was processed with Genescan 2.1 and Genotyper 1.1 software.
The Genome Scan
A genome scan was performed in the population of Tristan da Cunha using 274 polymorphic microsatellite markers chosen from among those developed at Oxford (Reed et al. (1994) Nature Genetics 7:390), Genethon (Dib et al. (1996) Nature 380:152) and the Cooperative Human Linkage Center (CHLC, Murray et al. (1994) Science 265:2049). Markers with heterozygosity values of 0.75 or greater were selected to cover all the human chromosomes, as well as for ease of genotyping and size of PCR product for multiplexing of markers on gels. Fifteen multiplexed sets were used to provide a ladder of PCR products in each of three dyes when separated by size. Published distances were used initially to estimate map resolution. More accurate genetic distances were calculated using the study population as the data was generated. The 274 markers gave an average 14 cM interval for the genome scan.
Linkage analysis
Parametric linkage analyses of marker data were conducted using the methods of Haseman and Elston (1972) Behav. Genet. 2:3, and FASTLINK (Schaffer et al. (1996) Hum. Hered. 46:226), assuming a dominant mode of transmission with incomplete penetrance. Linkage to three primary phenotypes including asthma diagnosis (history), airway responsiveness (PC20<4 mg/ml for methacholine challenge) and atopy (one or more skin-prick test which yielded a wheal diameter >3 mm) and combinations of these, were tested.
Small scale yeast artificial chromosome (YAC) DNA preparation
Small scale isolation of YAC DNA for STS mapping was done by a procedure which uses glass beads and physical shearing to damage the yeast cell wall (Scherer and Tsui (1991) Cloning and analysis of large DNA molecules, In Advanced Techniques in Chromosome Research. (K. W. Adolph, ed.) pp. 33-72. Marcel Dekker, Inc. New York, Basel, Hong Kong.)
YAC block prep and pulsed field gel electrophoresis (PFGE)
A 50 ml culture of each YAC was grown in 2.times. AHC at 30.degree. C. The cells were pelleted by centrifugation and washed twice in sterile water. After resuspension of the cells in 4 ml of SCEM (1 M sorbitol, 0.1 M sodium citrate (pH 5.8), 10 mM EDTA, 30 mM .beta.-mercaptoethanol), 5 ml of 1.2% low melting temperature agarose in SCEM was added, mixed, pipetted into 100 ml plug molds and allowed to solidify.
Plugs were incubated overnight in 50 ml of SCEM containing 30 U/ml lyticase (Sigma). Plugs were rinsed 3 times in TE (10 mM Tris pH 8.0, 1 mM EDTA) and incubated twice for 12 hours each at 50.degree. C. in lysis solution (0.5 M EDTA, pH 8.0; 1% w/v sodium lauryl sarcosine; 0.5 mg/ml proteinase K). They were washed 5 times with TE and stored in 0.5 M EDTA (pH 8.0) at 4.degree. C.
YACs and yeast chromosomes were separated on pulsed field gels using a CHEF Mapper (BIO-RAD) and according to methods supplied by the manufacturer, then transferred to nitrocellulose. YACs which comigrated with yeast chromosomes were visualized by hybridization of the blot with radiolabelled YAC vector sequences (Scherer and Tsui (1991) supra.)
Hybridization of YAC DNA to bacterial artificial chromosome (BAC) and cosmid grids
Size-purified YAC DNA was prepared by pulsed field gel electrophoresis on a low melting temperature Seaplaque GTG agarose (FMC) gel, purified by GeneClean (BIO101) and radiolabeled for 30 mins with .sup.32 P-dCTP using the Prime-It II kit (Stratagene). 50 .mu.l of water was added and unincorporated nucleotide was removed by Quick Spin Column (Boehringer Mannheim). 23 .mu.l of 11.2 mg/ml human placental DNA (Sigma) and 36 .mu.l of 0.5 M Na.sub.2 HPO.sub.4, pH 6.0 were added to the approximately 150 .mu.l of eluant. The probe was boiled for 5 mins and incubated at 65.degree. C. for exactly 3 hours, then added to the prehybridized gridded BAC (Shizuya et al. (1992) Proc. Natl. Acad. Sci. 89:8794; purchased from Research Genetics) or chromosome 11 cosmid [Resource Center/Primary Database of the German Human Genome Project, Berlin; Lehrach et al. (1990), In Davies, K. E. and Tilghman, S. M. (eds.), Genome Analysis Volume 1: Genetic and Physical Mapping. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp. 39-81] filters in dextran sulfate hybridization mix (10% dextran sulfate, 1% SDS, 1 M NaCl). Hybridizations were at 65.degree. C. for 12-48 hours, followed by 2 washes at room temperature in 2.times. SSC for 10 mins each, and 3 washes at 65.degree. C. in 0.2.times. SSC, 0.2% SDS for 20 mins each.
Metaphase fluorescence in situ hybridization (FISH) and direct visual in situ hybridisation (DIRVISH)
Metaphase FISH was carried out by standard methods (Heng and Tsui (1994) FISH detection on DAPI banded chromosomes. In Methods of Molecular Biology: In Situ Hybridisation Protocols (K. H. A. Choo, ed.) pp. 35-49. Human Press, Clifton, N.J.). High resolution FISH, or DIRVISH, was used to map the relative positions of two or more clones on genomic DNA. The protocol used was as described by Parra and Windle (1993) Nature Genet. 5:17. Briefly, slides containing stretched DNA were prepared by adding 2 .mu.l of a suspension of normal human lymphoblast cells at one end of a glass slide and allowing to dry. 8 .mu.l lysis buffer (0.5% SDS, 50 mM EDTA, 200 mM Tris-HCL, pH 7.4) was added and the slide incubated at room temperature for 5 minutes. The slide was tilted so that the DNA ran down the slide, then dried. The DNA was fixed by adding 400 .mu.l 3:1 methanol/acetic acid. Probes were labeled either with biotin or with digoxygenin by standard nick translation (Rigby et al. (1977) J. Mol. Biol. 113:237). Hybridization and detections were carried out using standard fluorescence in situ hybridization techniques (Heng and Tsui (1994) supra.). Results were visualised using a Mikrophot SA microscope (Nikon) equipped with a CCD camera (Photometrics). Images were recorded using Smartcapture software (Vysis).
Gap filling
Clones flanking gaps in the map were end cloned by digestion with enzymes that do not cut the respective vector sequences (NsiI for BAC clones and XbaI for PAC clones), followed by religation and transformation into competent DH5.alpha.. Clones which produced two end fragments and plasmid vector upon digestion with NotI and NsiI or XbaI were sequenced. Gaps in the tiling path were filled by screening a gridded BAC library with the end clone probes or by screening DNA pools of a human genomic PAC library (loannou et al. (1994) Nature Genetics 6:84; licensed from Health Research, Inc.) by PCR using primers designed from end clone sequences.
Direct cDNA selection
Direct cDNA selection (Lovett et al., (1991) Proc. Natl. Acad. Sci. 88:9628) was carried out using cDNA derived from both adult whole lung tissue and fetal whole lung tissue (Clontech). 5 .mu.g of Poly(A)+ RNA was converted to double stranded cDNA using the Superscript Choice System for cDNA synthesis and the supplied protocol (Gibco BRL). First strand priming was achieved by both oligo(dT) and random hexamers. The resulting cDNA was split into 2 equal aliquots and digested with either MboI or TaqI prior to the addition of specific linker primers. Linker primers for MboI-digested DNA were as described by Morgan et a/. (1992) Nucleic Acid Res. 20:5173. Linker primers for TaqI-digested DNA were a modification of these: (SEQ ID NO:336) Taq1a: 5'-CGAGAATTCACTCGAGCATCAGG; (SEQ ID NO:337) Taq1b: 5'-CCTGATGCTCGAGTGAATTCT. The modified cDNA was ethanol precipitated and resuspended in 200 .mu.l of H.sub.2 O. 1 .mu.l of cDNA was amplified with the linker primer MboI b in a 100 .mu.l PCR reaction. The resulting cDNA products, approximately 1 .mu.g, were blocked with 1 .mu.g of COT1 DNA (Gibco BRL) for 4 hours at 600C in 120 mM NaPO.sub.4 buffer, pH 7.0.
Approximately 1 .mu.g of the appropriate genomic clones was biotinylated using the BioNick Labeling System (Gibco BRL). Unincorporated biotin was removed by spin column chromatography. Approximately 100 ng of biotinylated genomic DNA was denatured and allowed to hybridize to 1 .mu.g of blocked cDNA in a total volume of 20 .mu.l in 120 mM NaPO.sub.4 for 60 hours at 600C under mineral oil. After hybridization, the biotinylated DNA was captured on streptavidin-coated magnetic beads (Dynal) in 100 .mu.l of binding buffer (1 M NaCl, 10 mM Tris, pH 7.4, 1 mM EDTA) for 20 minutes at room temperature with constant rotation. Two 15 minute washes at room temperature with 500 .mu.l of 1.times. SSC/0.1% SDS were followed by four washes for 20 minutes at 65.degree. C. with 500 ul of 0.1.times. SSC/0.1% SDS with constant rotation. After each wash, the beads were collected on the side of the tube using magnet separation and the supernatant was removed with a pipette. Following the last wash, the beads were briefly rinsed once with wash solution prior to eluting the bound cDNA with 50 .mu.l of 0.1 M NaOH for 10 minutes at room temperature. The supernatant was removed and neutralized with 50 .mu.l 1 M Tris pH 7.4. The primary selected cDNA was desalted using a Sephadex G-50 column (Boehringer Mannheim). PCR was performed on 1, 2, 5, and 10 .mu.l of eluate with MboI b primers. Amplified products were analyzed on a 1.4% agarose gel. The reaction with the cleanest bands and least background was scaled up to produce approximately 1 .mu.g of primary selected cDNA. This amplified primary selected cDNA was blocked with 1 .mu.g of COT1 at 60.degree. C. for 1 hour followed by a second round of hybridization to 100 ng of the appropriate genomic DNA under the same conditions as the first round of selection. Washing of the bound cDNA, elution, and PCR of the selected cDNA was identical to the first round. 1 .mu.l of PCR amplified secondary selected cDNA was cloned using the TA cloning system according to the manufacturers protocol (Invitrogen). Colonies were picked into 96-well microtiter plates and grown overnight prior to sequencing.
Exon Trapping
Exon trapping was performed by the method of Buckler et al. (1991, Proc. Natl. Acad. Sci. USA 88:4005) with modifications described in Church et al., (1994) Nature Genetics 6:98. Each BAC clone of the minimal set of clones required to the cover the ASTH1 region (i.e. the tiling path) was subject to exon trapping separately. Briefly, restriction fragments (PstI or BamHI/BgIII) of each cosmid were shotgun subcloned into PstI- or BamHI-digested and phosphatase-treated psPL3B which had been modified as in Burns et al. (1995) Gene 161:183 (GIBCO BRL). Ligations were electroporated into ElectroMax HB101 cells (Gibco BRL) and plated on 20 cm diameter LB ampicillin plates. DNA was prepared from plates with >2000 colonies by collection of the bacteria in LB ampicillin liquid and plasmid DNA purification by a standard alkaline lysis protocol (Sambrook et al. (1989) sLipra.) 5 .mu.g of DNA from each plasmid pool preparation were electroporated into Cos 7 cells (ATCC) and RNA harvested using TRIZOL (Gibco BRL) after 48 hours of growth. RT-PCR products were digested with BstXI prior to a second PCR amplification. Products were cloned into pAMP10 (Gibco BRL) and transformed into DH5 cells (Gibco BRL). 96 colonies per BAC were picked and analyzed for insert size by PCR.
Northern blot hybridisation
Northern hybridisation was performed using Multiple Tissue Northern (MTN) blots (Clontech). DNA probes were radioactively labeled by random priming [Feinberg and Vogelstein (1984) Anal. Biochem. 137:266] using the Prime-It II kit (Stratagene). Hybridizations were performed in ExpressHyb hybridisation solution (Clontech) according to the manufacturer's recommendations. Filters were exposed to autoradiographic film overnight or for 3 days.
cDNA library screening
Phage cDNA libraries were plated and screened with radiolabeled probes (exon trapping or cDNA selection products amplified by PCR from plasmids containing these sequences) by standard methods (Sambrook et al. (1989) supra.)
Rapid amplification of cDNA ends (RACE)
RACE libraries were constructed using polyA+ RNA and the Marathon cDNA amplification kit (Clontech). Nested RACE primer sets were designed for each cDNA or potential gene fragment (trapped exon, predicted exon, conserved fragment, etc). The RACE libraries were tested by PCR using one primer pair for each potential gene fragment; the two strongly positive libraries were chosen for RACE experiments.
Genomic sequencing
DNA from cosmid, PAC, and BAC clones was prepared using Qiagen DNA prep kits and further purified by CsCl gradient. DNA was sonicated and DNA fragments were repaired using nuclease BAL-31 and T4 DNA polymerase. DNA fragments of 0.8-2.2 kb were size-fractionated by agarose gel electrophoresis and ligated into pUC9 vector. Inserts of the plasmid clones were amplified by PCR and sequenced using standard ABI dye-primer chemistry.
ABI sample file data was reanalyzed using Phred (Phil Green, University of Washington) for base calling and quality analysis. Sequence assembly of reanalyzed sequence data was accomplished using Phrap (Phil Green, University of Washington). Physical gaps between assembled contigs and unjoined but overlapping contigs were identified by inspection of the assembled data using GFP (licensed from Baylor College of Medicine) and Consed (Phil Green, University of Washington). Material for sequence data generation across gaps was obtained by PCR amplification. Low coverage regions were resequenced using dye-primer and dye-terminator chemistries (ABI). Final base-perfect editing (to >99% accuracy) was accomplished using Consed.
Single stranded conformational polymorphism (SSCP) analysis
PCR primers flanking each exon of the ASTH1I and ASTH1J genes, or more than one primer pair for large exons, were designed from genomic sequence generated using Primer (publicly available from the Whitehead Institute for Biomedical Research) or Oligo 4.0 (licensed from National Biosciences). Radioactive SSCP was performed by the method of Orita et al. (1989, Proc. Natl. Acad. Sci. 86:2766). Briefly, radioactively labeled PCR products between 150 and 300 bp and spanning exons of the ASTH1I and ASTH1J genes were generated from a set of asthma patient and control genomic template DNAs, by incorporating .alpha.-.sup.32 P dCTP in the PCR. PCR reactions (20 .mu.l) included 1.times. reaction buffer, 100 .mu.M dNTPs, 1 .mu.M each forward and reverse primer, and 1 unit Taq DNA polymerase (Perkin-Elmer) and 1 .mu.Ci .alpha.-.sup.32 P dCTP. A brief denaturation at 94.degree. C. was followed by 30-32 cycles of: 94.degree. C. for 30 sec, 30 sec at the annealling temperature, and 72.degree. C. for 30 sec; followed by 5 mins at 72.degree.. Radiolabeled PCR products were diluted 1:20 in water, mixed with an equal volume of denaturing loading dye (95% formamide, 0.25% bromophenol blue), and denatured for 10 minutes at 80.degree. C. immediately prior to electrophoresis. 0.5.times. MDE (FMC) gels with and without 8% glycerol in 1.times. TBE were run at 8-12 Wafts for 16-20 hours at room temperature. Dried gels were exposed to autoradiographic film (Kodak XAR) for 1-2 days at -80.degree. C. PCR products from individuals carrying SSCP variants were subcloned into the PCR2.1 or pZeroBlunt plasmid vector (Invitrogen). Inserts of the plasmid clones were amplified by PCR and sequenced using standard ABI dye-primer chemistry to determine the nature of the sequence variant responsible for the conformational changes detected by SSCP.
Fluorescent SSCP was carried out according to the recommended ABI protocol (ABI User Bulletin entitled `Multi Color Fluorescent SSCP`). Unlabeled PCR primers were used to amplify genomic DNA segments containing different exons of the ASTH1I or ASTH1J genes, in patient or control DNA. Nested fluorescently labeled (TET, FAM or HEX) primers were then used to amplify smaller products, 150 to 300 bp containing the exon or region of interest. Amplification was done using a `touchdown` PCR protocol, in which the annealing temperature decreased from 57.degree. C. to 42.degree. C., and Amplitaq Gold polymerase (Perkin Elmer, Cetus). In most cases the fluorescently labeled primers were identical in sequence to those used for conventional radioactive SSCP. The fluorescent PCR products were diluted and mixed with denaturing agents, GeneScan size standard (Genescan 500 labelled with Tamra) and Blue dextran dye. Samples were heated at 90.degree. C. and quick chilled on ice prior to loading on 6.5% standard or 0.5.times. MDE (manufacturer) polyacrylamide gels containing 2.5% glycerol and run using externally temperature controlled modified ABI 377 instruments. Gels were run at 1240 V and 20.degree. C. for 7-9 hrs and analyzed using GeneScan software (ABI).
Comparative (heterozygote detection) sequencing
Unlabeled PCR primers were used to amplify genomic DNA segments containing different exons of the ASTH1I or ASTH1J genes, from patient or control DNAs. A set of nested PCR primers was then used to reamplify the fragment. Unincorporated primers were removed from the PCR product by Centricon-100 column (Amicon), or by Centricon-30 column for products less than 130 bp. The nested primers and dye terminator sequencing chemistry (ABI PRISM dye terminator cycle sequencing ready reaction kit) were then used to cycle sequence the exon and flanking region. Volumes were scaled down to 5 .mu.l and 10% DMSO added to increase peak height uniformity. Sequences were compared between samples and heterozygous positions detected by visual inspection of chromatograms and using Sequence Navigator (licensed from ABI).
For some exons, PCR products were also compared by subcloning and sequencing, and comparison of sequences for ten or more clones.
Results
Genome scanning and linkage analysis
A genome scan was performed using polymorphic microsatellite markers from throughout the human genome, and DNA isolated from blood samples drawn from the inhabitants of Tristan da Cunha. Linkage analysis, an established statistical method used to map the locations of genes and markers relative to other markers, was applied to verify the marker orders and relative distances between markers on all human chromosomes, in the Tristan da Cunha population. Linkage analysis can detect cosegregation of a marker with disease, and was used as a means to detect genes influencing the development of asthma in this population. The most highly significant linkage in the genome scan (p=0.0001 for history of asthma and p=0.0009 for methacholine challenge) was obtained at D11S907, a marker on the short arm of chromosome 11. This significant linkage result indicated that a gene influencing predisposition to asthma in the Tristan da Cunha population was located near D11S907.
Replication of this finding was obtained in a collection of asthma families from Toronto, in which D11S907 and several nearby markers were tested for linkage. The significant linkage seen (p=0.001 for history of asthma and p=0.05 for methacholine challenge) supported the mapping of an asthma gene near D11S907 and indicated that the gene was likely to be relevant in the more diverse outbred Toronto group as well as in the inbred population of Tristan da Cunha.
The approximate genetic location of the ASTH1 gene in the Tristan da Cunha population was confirmed by genotyping and analyzing data from several markers near D11 S907, spaced at intervals no greater than 5 cM across a possible linked region of about 30 cM. Sib-pair and affected pedigree member linkage analyses of these markers yielded confirmatory evidence for linkage and refined the genetic interval.
Physical mapping at ASTH1: YAC contig construction
Yeast artificial chromosome (YAC) clones were derived from the CEPH megaYAC library (Cohen et al. 1993 Nature 366:698). Individual YAC addresses were obtained from a public physical map of CEPH megaYAC STS (sequence tagged site; Olson et al. (1989) Science 245:1434) mapping data maintained by the Whitehead Institute and accessible through the world wide web (Cohen et al. 1993. supra.; http://www-genome.wi.mit.edu/cgi-bin/contig/phys.sub.-- map). YAC clones spanning or overlapping other YACs containing D11S907 were chosen for map construction; STSs mapping to these YACs were used for map and clone verification. Some YACs annotated in the public database as being chimeric were excluded from the analyses. Multiple colonies of each YAC, obtained from a freshly streaked plate inoculated from the CEPH megaYAC library masterplate, were scored using STS markers from the ASTH1 region. These markers included polymorphic microsatellite repeats, expressed sequence tags (ESTS) and STSs. Comparison of STS mapping data for each clone with the public map allowed choice of the individual clone which retained the greatest number of ASTH1 region STSs, and was therefore least likely to be deleted. YAC addresses for which clones differed in STS content were interpreted to be prone to deletion; those for which a subset of clones contained no ASTH1 region STSs were presumed to be contaminated with yeast cells containing a YAC from another region of the genome. Chimerism of the chosen clones was assessed by metaphase fluorescent in situ hybridization (FISH). Their sizes were determined by pulsed field gel electrophoresis (PFGE), Southern blotting and hybridization with a YAC vector probe. The PFGE analyses also showed that no YAC clone chosen contained more than one yeast artificial chromosome.
An STS map based on assuming the least number of deletions in the YAC clones was generated. The STS marker order was in agreement with that of the Whitehead map. The STS retention pattern of individual YACs, however, was slightly different from that of the public data. In general, the chosen clones were positive for a greater number ASTH1 region markers, showing that the data set was likely to have fewer false negatives than the public map. Non-chimeric YAC clones spanning the region of greatest interest were chosen for use as hybridization probes for the identification of smaller BAC, PAC, P1 or cosmid clones from the region.
Conversion to a plasmid-based clone map
The YAC map at ASTH1 provided continuous coverage of a 4 Mb region, the central 1 Mb of which was of greatest interest. YAC clones comprising a minimal tiling path of this region were chosen, and the size purified artificial chromosomes were used as hybridization probes to identify BAC and cosmid clones. Gridded filters of a 3.times. human genomic BAC library and of a human chromosome 11-specific cosmid library were hybridized with radiolabeled purified YAC. Clones corresponding to the grid coordinates of the positives were streaked to colony purity, and filters gridded with four clones of each BAC or cosmid. These secondary filters were hybridized with size-purified YAC DNAS. A proportion of both the BACs and cosmids were found to be non-clonal by these analyses. A positively hybridizing clone of each was chosen for further analysis.
The BAC and cosmid clones were STS mapped to establish overlaps between the clones. The BACs were further localized by DIRVISH. BACs which did not contain an STS marker were mapped in pairwise fashion by simultaneous two-color DIRVISH with another BAC. The map produced had three gaps which were subsequently filled by end cloning and hybridization of the end clones to a human genomic PAC library. Genetic refinement of the ASTH1 region had occurred concurrently with mapping, rendering it unnecessary to extend the BAC-contigged region. Mapping data was recorded in ACeDB (Eeckman and Durbin (1995) Methods Cell Biol. 48:583).
Genomic sequencing and gene prediction
A minimal tiling path of BAC and cosmid clones was chosen for genomic sequencing. Over 1 Mb of genomic sequence was generated at ASTH1. On average, sequencing was done to 12.times. coverage (12 times redundancy in sequences). Marker order was verified relative to the STS map.
BLAST searches (Altschul et al. (1990) supra.) were performed to identify sequences in public databases that were related to those in the ASTH1 region. Sequence-based gene prediction was done with the GRAIL [Roberts (1991) Science 254:805] and Geneparser [Snyder and Stormo (1993) Nucleic Acids Res. 21: 607] programs. Genomic sequence and feature data was stored in ACeBD.
Development of new microsatellite markers for genetic refinement of the ASTH1 region
Additional informative polymorphic markers were important for the genetic refinement of the ASTH1 region. `Saturation` cloning of every microsatellite in the 1 Mb region surrounding D11S907 was performed. Plasmid libraries were constructed from PFGE purified DNA from each YAC, prescreened with a primer from each known microsatellite marker, then screened with radiolabeled (CA)15 or a pool of trinucleotide and tetranucleotide repeat oligonucleotides. The plasmid inserts were sequenced, the set of sequences compared with those of the known microsatellite markers in the region, using Power assembler (ABI) or Sequencher (Alsbyte). Primer pairs flanking each novel microsatellite repeat were designed, and the heterozygosity of each new marker was tested by Batched Analysis of Genotypes (BAGs; LeDuc et al., 1995, PCR Methods and Applications 4:331). Additional microsatellites were found by analysis of the genomic sequence in AceDB. Table 1 lists all the microsatellite markers used for genotyping in the ASTH1 region and their repeat type, source and primers. Table 1B lists some repeat sequences.
TABLE 1__________________________________________________________________________Polymorphic microsatellite markers in the ASTH1 regionSEQ ID MARKER PRIMER 1__________________________________________________________________________160. 110O5GT1 CTGCTGTGGACGAATAGG161. TCAATATAATCTTGCTTAACTTGG162. 139C7GT1 GACCTGTTTGGGTTGATTTCAG163. GTTTCTTACAGTGTCTTGCTATCACATCACC164. 171L24AT1 GAGGACTGGCAGTACCAAGTAAAC165. GTTTCTTTGGTTCATTCTAAGATGGCTGG166. 253E6GT1 GCTGAGGCAGGAGAAAAGACAAG167. GTTTCTTCATGCAAAGGTCAGGAGGTAGG168. 253E6TE1 GTTGCTTCCAGACGAGGTACATG169. GTTTCTTCAATGGCTCCACAAACATCTCTG170. 253E6TR1 AGGTTTAGGGGACAGGGTTTGG171. GTTTCTTTCCTGGCTAACACGGTGAAATC172. 65P14 GTTTCTTATTGCCTCCTCCCAAAATTC173. AGAGGCCACTGGAAGACGAA174. 65P14GT1 AACTGGAGTCAGGCAAAACGTG175. GTTTCTTTGGCTGGTAAGGAAAGAAACCAC176. 65P14TE1 GGCTAGGTTCATAAACTCTGTGCTG177. GTTTCTTGATTGTTTGAGATCCTTGACCCAG178. 65P14TE2 GCCGAAATCACAACACTGCATC179. GTTTCTTGATTCTGCTCTTACTCTTGCCCC180. 65P14TR1 GTAATAGAACCAAAGGGCTGAGAC181. GTTTCTTCGGAGTCAGACCTTACATTGTTGAG182. 774F ATCTCCCTGCTACCCACCTT183. GTTTCTTGTTTTCAGTGAGTTTCTGTTGGG184. 774J GTGTGCCAAACAACATTTGC185. GTTTCTTCAAGCCATCAAGCTAGAGTGG186. 774L GGGCTTTTAAACCCTTATTTAACC187. GTTTCTTAGGTGATCTCAGAGCCACTCA188. 774N AGGGCAGGTGGGAACTTACT189. GTTTCTTTGGAGTCAGTTGAGCTTTCTACC190. 774O TGAACTTGCCTACCTCCCAG191. GTTTCTTAGCATATATCCTTACACAAGCACA192. 774T CATGGTTCCAAAGGCAAGTT193. GTTTCTTTTGAGGCTGAATGAGCTGTG194. 86J5AT2 ACAGGTGGGAAGACTGAATGTC195. GTTTCTTGCAGTACACATCACATGACCTTG196. 86J5CA1 GAAATAGGCGGAAACTGGTTC197. GTTTCTTCGTTGTGGTTGTTCAGAAAGG198. 86J5GT1 GGTCAAGTGTTCAGAACGCATC199. GTTTCTTGCAGGGATTATGCTAGGTCTGTAG200. 86J5GT2 AGCACTTCTGAGGAAGGGACAC201. GTTTCTTAGGGCAGGCAGACATACAAAC202. 86J5TE1 GCCAATGTGTTCCTAGAGCGAC203. GTTTCTTTTAAAGGGGGTAGGGTGTCACC204. 8E.PENTA1 GGAAGGGAAAAGGACAAGGTTTTG205. GTTTCTTAGCAAGAGCACTGGTGTAGGAGTC206. 8E04DO5 GCTTTTCAAGCACTTGTCTC207. TGGGATTGTGACTTACCATG208. 8O16GT1 ACTTGGTGTCTTATAGAAAGGTG209. GTTTCTTAGCTGTGTTTGCTGCATC210. 8O16GT2 AGATGTGTGATGAGATGCAG211. GTTTCTTCAAATAGTGCAACAAACCC212. AFM198YB10(G) TGTCATTCTGAAAGTGCTTCC213. GTTTCTTCTGTAACTAACGATCTGTAGTGGTG214. AFM205YG5(G) TATCAAGGTAATATAGTAGCCACGG215. AGGTCTTTCATGCAGAGTGG216. AFM206XB2(G) ATTGCCAAAACTTGGAAGC217. AGGTGACATATCAAGACCCTG218. AFM283WH9(G) TTGTCAACGAAGCCCAC219. GTTTCTTGCAAGATTGTGTGTATGGATG220. AFM324YH5(G) GCTCTCTATGTGTTTGGGTG221. AAGAGTACGCTAGTGGATGG222. AFMA154ZD1(G) TCCATTAGACCCAGAAAGG223. GTTTCTTCACCAGGCTGAGATGTTACT224. ASMI14 AATCGTTCCTTATCAGGTAATTTGG225. GTTTCTTCAAAGAAAGCAATTCCATCATAACA226. ASMI14T GCATTTGTTGAAGCAAGCGG227. CTTTGTTCCTTGGCTGATGG228. CA11.sub.-- 11 AATAGTACCAGACACACGTG229. CAATGGTTCACAGCCCTTTT230. CA39.sub.-- 2 AGCCTGGGAGACAGAGTGAG231. GTTTCTTGCACTTTTTGGGGAAGGTG232. CD59(L) GTTCCTCCCTTCCCTCTCC233. GTTTCTTTCAGGGACTGGATTGTAG234. D11S1301(U) GTGTTCTTTATGTGTAGTTC235. GTTTCTTGGCAACAGAGTGAGACTCA236. D11S1751(G) GTGACATCCAGTGTTGGGAG237. GTTTCTTCCTAAGCAAGCAAGCAATCA238. D11S1776(G) AAAGGCAATTGGTGGACA239. GTTTCTTTTCAATCCTTGATGCAAAGT240. D11S1900(U) GGTGACAGAGCAAGATTTCG241. GTTTCTTGTAGAGTTGAGGGAGCAGC242. D11S2008/D11S1392 CATCCATCTCATCCCATCAT (C)243. GTTTCTTTTCACCCTACTGCCAACTTC244. D11S2014(C) CCGCCATTTTAGAGAGCATA245. GTTTCTTTTCTGGGACAATTGGTAGGA246. D11S4300(G) TTTGTGTTATTATTTCAGGTGC247. GTTTCTTGTTTTTTGTTTCA GTTTAGGAAC248. D11S907(G) CATACCCAAATCGTTCTCTTCCTC249. GTTTCTTGGAAAAGCAAAG GCATCGTAGAG250. D11S935(G) TACTAACCAAAAGAGTTGGGG251. CTATCATTCAGAAAATGTTGGC252. GATA-P18492(C) GTATGGCAGTAGAGGGCATG253. AAGGTTACATTTCAAGAAATAAAGT254. GATA-P6915(C) CTGTTCAGGCCTCAATATATACC255. AAGAGGATAGGTGGGGTTTG256. L19CA3 CCTCCCACCTAGACACAAT257. ATATGATCTTTGCATCCCTG258. L19PENTA1 AAGAAAGACCTGGAAGGAAT259. AAACAGCAAAACCTCATCTC260. L19TETRA5 CCACCACTTATTACCTGCAT261. TGAATGAATGAATGAACGAA262. LMP2 AACTGTGATTGTGCCACTGCACTC263. GTTTCTTCACCGCCTTTATCCCTCAAATG264. LMP3 GATGGGTGGAGGGCAGTTAAAG265. GTCAAGCAACTTGTCCAAGGCTAC266. LMP4 CAGGCTATCAGTTTCCTTTGGAG267. GGCAGGTAATACTGGAGAATTAGG268. LMP7 GACGGATCTCAGAGCCACTC269. GTTTCTTAAAAGATAAGGGCTTTTAAACC270. T18.sub.-- 5 AGTTTCACAGCTTGTTATGG271. GGTTGATGAAGTGAGACTTT272. T29.sub.-- 9 ATGGTGGATGCATCCTGTG273. GTTTCTTGTATTGACTCCTCCTCTGC274. 774L CAGTAAACAT275. TGTTGAGTGG276. 774N TCTCCTCAATGTGCATGT277. ATTCTACATA278. ASMI14 GTGTTTGCAT279. ACAAGTTGGC280. CA11.sub.-- 11 TAGTACCAGA281. TACATCCAAGAAAA__________________________________________________________________________ The source of marker was Sequana Therapeutics, Inc. unless a letter in parenthesis is indicated after the name, where G = Genethon; L = Nothen and Dewald (1995) Clin. Genet. 47:165; U = the Utah genome center, see: The Utah Marker Development Group (1995) Am. J. Hum. Genet. 57:619; c = the cooperative Human Lineage Center.
TABLE 1B__________________________________________________________________________SEQ Marker Repeat and flanking sequence__________________________________________________________________________282. CA39.sub.-- 2 GAGACTCTGA(CA)nAATATATATA283. 774F TGTTGATCGC(CA)nAACCAAAATC284. 774J AATGCATGTA(TG)2TATA(TG)nGTGTGGTATG(TG)3TACATATG CG285. 774O CCTCCCAGAA(CA)n ATCATGATAA286. L19PENT AGACAGTCTCAAAAAAT(ATTTT)nAAAGAAAAAGCTGGATAAAT A1287. 65P14TE AACTAGCTTTAAGAAAATAAGAAGAAAAAGAAAGAAG(AAAG)2TAA 1 G(AAAG)nAGAAAGAAAAG(AAAG)nAAAAG(AAAG)nAGGAATGAT TGAC288. 65P14 CGCGCACATA(CA)nCCCTTTCTCT289. 774L CAGTAAACAT(CA)n TGTTGAGTGG290. 774N TCTCCTCAATGTGCATGT (GTGC)2 ATGA (GTGC)2 (AC)n ATTCTACATA291. ASMI14 GTGTTTGCAT (GT)n T (GT)3 ACAAGTTGGC292. CA11.sub.-- 11 TAGTACCAGA (CA)2 CG(TG)2 (CA)2 GGCAAGCG (CA)n C1234567890 - (CA)2 TACATCCAAGAAAA__________________________________________________________________________
Genetic refinement of the ASTH1 region
The microsatellite markers isolated from YACs from the ASTH1 region were genotyped in both the Tristan da Cunha and Toronto cohorts. Genetic refinement of the ASTH1 region was accomplished by applying the transmission/disequilibrium test (TDT; Spielman et al. (1993) Am. J. Hum. Genet. 52:506) to genetic data from the Tristan and Toronto populations, at markers throughout the ASTH1 region. The TDT statistic reflects the level of association between a marker allele and disease status. A multipoint version of the TDT test controls for variability in heterozygosities between loci, and results in a smoother regional TDT curve than would a plot of single locus TDT data. Significance of a TDT value is determined by means of the .chi..sup.2 test; A .chi..sup.2 value of 3.84 or greater is considered statistically significant at a probability level of 0.05.
The Toronto TDT peak is located at marker D11S2008 (.chi..sup.2 =11.6, p <0.0001). The marker allele in disequilibrium is fairly rare (freq=6%), representing the fourth most common allele at this marker. The relative risk of affection vs. normal for this allele is 5.25. This is also the peak marker for linkage and linkage disequilibrium in Tristan da Cunha, indicating that the ASTH1 gene is very close to this marker. The markers defining the limits of linkage disequilibrium were D11 S907 and 65P14TE1. The physical size of the refined region is approximately 100 kb.
A significant TDT test reflects the tendency of alleles of markers located near a disease locus (also said to be in "linkage disequilibrium" with the disease) to segregate with the disease locus, while alleles of markers located further from the disease locus segregate independently of affection status. An expectation that derives from this is that a population for which a disease gene (ie a disease predisposing polymorphism) was recently introduced would show statistically significant TDT over a larger region surrounding the gene than would a population in which the mutant gene had been segregating for a greater length of time. In the latter case, time would have allowed more opportunity for markers in the vicinity of the disease gene to recombine with it. This expectation is fulfilled in our populations. The Tristan da Cunha population, founded only 10 generations ago, shows a broader TDT curve than does the set of Toronto families, which are mixed European in derivation and thus represent an older and more diverse, less recently established population.
Gene isolation and characterization
The tiling path of BACs, cosmids and PAC clones was subjected to exon trapping and cDNA selection to isolate sequences derived from ASTH1 region genes. Exon trap clones were isolated on the basis of size and ability to cross-hybridize. Approximately 300 putatively non-identical clones were sequenced. cDNA selection was performed with adult and fetal lung RNA using pools of tiling path clones. The cDNA selection clones were sequenced and the sequences assembled with those of the exon trap clones. Representative exon trapping clones spanning each assembly were chosen, and arranged as "masterplates" (96-well microtitre dishes) of clones. Exon trap masterplate clones and cDNA selection clones were subjected to expression studies.
Human multi-tissue Northern blots were probed with PCR products of masterplate clones. In some cases, exon trapping clones did not detect RNA species, either because they did not represent expressed sequences, or represented genes with very restricted patterns of expression, or due to small size of the exon probe.
Masterplate clones detecting discrete RNA species on Northern blots were used to screen lambda phage based cDNA libraries chosen on the basis of the expression pattern of the clone. The sequences of the cDNAs were determined by end sequencing and sequence walking. cDNAs were also isolated, or extended, by 5' and 3' rapid amplification of cDNA ends (RACE). In most cases, 5' RACE was necessary to obtain the 5' end of the cDNA.
ASTH1I and ASTH1J were detected by exon trapping. ASTH1I exons detected a 2.8 kb mRNA expressed at high levels in trachea and prostate, and at lower levels in lung and kidney. ASTH1I exons were used as probes to screen prostate, lung and testis cDNA libraries; positive clones were obtained from each of these libraries. Isolation of a ASTH1I cDNA clone from testis demonstrates that this gene is expressed in this tissue, and possibly others, at a level not detectable by Northern blot analysis.
ASTH1J exons detected a 6.0 kb mRNA expressed at high levels in the trachea, prostate and pancreas and at lower levels in colon, small intestine, lung and stomach. Pancreas and prostate libraries were screened with exon clones from ASTH1J. cDNA clone end sequences were assembled using Sequencher (Alsbyte) with the sequences of the exon trapped clones, producing sequence contigs used to design sequence walking and RACE primers. The additional sequences produced by these methods were assembled with the original sequences to produce longer contigs of cDNA sequences. It was evident from the sequence assemblies that both ASTH1I and ASTH1J are alternatively spliced and/or have alternative transcription start sites at their 5' ends, since not all clones of either gene contained the same 5' sequence.
ASTH1J has three splice forms consisting of the alt1 form, found in prostate and lung cDNA clones, and in which the exons (illustrated in FIG. 1) are found in the order: 5' a, b, c, d, e, f, g, h, i 3'. A second form, alt2, in which the exon order is: 5' a2, b, c, d, e, f, g, h, i 3' was seen in a pancreas cDNA clone. A third form, alt3, contains an alternate exon, a3, between exons a2 and b. The start codon is within exon b, so that the open reading frame is identical for the three forms, which differ only in the 5' UTR. The ASTH1J cDNAs shown as SEQ ID NO:2 (form alt1); SEQ ID NO:3 (form alt2); SEQ ID NO:4 (form alt3) are 5427, 5510 and 5667 bp in length, respectively. The sequence of the entire protein coding region and alternate 5' UTRs are provided. The 3' terminus, where the polyA tail is added, varies by 7 bp between clones. The provided sequences are the longest of these variants. The encoded protein product is provided as SEQ ID NO:5.
ASTH1I was seen in three isoforms denoted as alt1, alt2, and alt3. The exons of ASTH1I and ASTH1J were given letter designations before the directionality of the cDNA was known, the order is different for the two genes. In the alt1 form of ASTH1I, exons are in the following order: 5' i, f, e, d, c, b, a 3'. In the alt2 form of ASTH1I, an alternative 5' exon, j, substitutes for exon i, with the following exon arrangement: 5' j, f, e, d, c, b, a 3'. The alt3 form of the gene has the exon order: 5' f, k, h, g, e, d, c, b, a 3'. The alternative splicing and start codons in each of exons i, f and e give the three forms of ASTH1I protein different amino termini. The common stop codon is located in exon a, which also contains a long 3' UTR. Two polyadenylation signals are present in the 3' UTR; some cDNA clones end with a polyA tract just after the first polyA signal and for others the polyA tract is at the end of the sequence shown. Since the sequences shown for the alt1, alt2, and alt3 forms of ASTH1I (2428 bp-2280 bp and 2498 bp; respectively) are close to the estimated Northern blot transcript size of 2.8 kb, these sequences are essentially full length.
EST matches
The nucleotide sequences of the alt1, alt2 and alt3 forms of ASTH1J and the alt1, alt2 and alt3 forms of ASTH1I were used in BLAST searches against dbEST in order to identify EST sequences representing these genes. Perfect or near perfect matches were taken to represent sequence identity rather than relatedness. Accession numbers T65960, T64537, AA055924 and AA055327 represent the forward and reverse sequences of two clones which together span the last 546 bp (excluding the polyA tail) of the 3' UTR of ASTH1I. No ESTs spanned any part of the coding region of this gene. One colon cDNA clone (accession number AA149006) spanned 402 bp including the last 21 bp of the ASTH1J coding region and part of the 3' UTR.
Intron/exon structure determination
The genomic organization of genes in the ASTH1 region was determined by comparison by BLAST of cDNA sequences to the genomic sequence of the region. The genomic sequence of the ASH1I region 5' to and overlapping ASTH1J, is provided in SEQ ID NO:1. Genomic structure of the ASTH1I and ASTH1J genes is shown in FIG. 1; the intron/exon junction sequences are in Table 2.
TABLE 2______________________________________Genomic organization of the ASTH1I and ASTH1Jgenes. *Exonic sequences are upper case, flanking - sequences lowercase. Size of Sequences at the ends of and exon flanking the exons of ASTH1ISEQ NO Exon (bp) and ASTH1J*______________________________________ASTH1I293. i >214 ggaggctgagCAGGGGTGCC...294. ...ACTCCCACAGgtacctgcag295. j >66 ...CTGCCCTCACgtaagcgcct296. f 125 gctgttgagGGTAATGTTG...297. ...CATCAGACAGgtgcgtaca298. k 226 ggctggtgagGAGGGGCTGA...299. ...CGCTCTGTGGgtgagcttca300. h 93 tgtggaatagCCCAATTACA...301. ...AGGGTGCTGAgtgagtagta302. g 79 ttcttttcagGCCCTCGTGT...303. ...TGCTGACCCGgtatggtggt304. e 232 tttggtgcagCCTGTGACTC...305. ...CGCACACAAGgtcagtgttc306. d 51 tctttcccagGTTACTCCTT...307. ...ATCAAAGACTgtaagtaacc308. c 69 tctatttcagATGCTGATTC...309. ...AGTAGAACAAgtaagtgcag310. b 196 ttttcaaaagGCCTCCAAAG...311. ...GAGCCCTGAGgtaagttaat312. a 1522 gctttttcagATACTACTAT...313. ...TAACATGTTCaactgtctgt314. a 146 tgttatatgcATTTATCTTC...315. ...GGTAAATGAGgtaagtcctg316. a2 229 tcttgttaagATCGCTCTCT...317. ...CCTTGCCCAGgttctcttaa318. a3 157 gcaatcgcacCTGCACACCC...319. ...ACTGCCCATTtctggtaaag320. b 100 cccctaacagATCATGATTC...321. ...ACGTGCAATGgtaagagggc322. c 246 tgttttgcagTTTCCAGTGG...323. ...AAGTGGAACGgtgactctct324. d 63 tccttcacagGCCAGTGCAG...325. ...GAACAAACTGgtg agtagta326. e 69 ttttttgtagAGCCTTCCAT...327. ...AGCACAGTAGgtaactaact328. f 69 atggccacagATTTGTTGGA...329. ...CTTCCTGTTGgtaagctgtc330. g 63 ttctccttagCAGAGTCACC...331. ...AAAAAGCACAgtaagttggc332. h 196 ttttcatcagACCCGAGAGG...333. ...GAGCTATGAGgtgaggagtt334. i 4457 tttgttacagATATTACTAC...335. ...AGCCTGGAAAtgcgtgtttc______________________________________
The deduced ASTH1I and ASTH1J proteins
The protein encoded by ASTH1J (SEQ ID NO:5) is 300 amino acids in length. A BLASTP search of the protein sequence against the public nonredundant sequence database (NCBI) revealed similarity to one protein domain of transcription factors of the ets family. The ets family, named for the E26 oncoprotein which originally defined this type of transcription factor, is a group of transcription factors which activate genes involved in a variety of immunological and other processes, or implicated in cancer. The family members most similar to ASTH1I and ASTH1J are: ETS1, ESX, ETS2, ELF, ELK1, TEL, NET, SAP-1, NERF and FLI. Secondary structure analysis and comparison of the protein sequence to the crystal structure of the human ETS1-DNA complex (Werner et al. (1995) Cell 83:761) confirmed that it has a winged helix turn helix motif characteristic of some DNA binding proteins which are transcription factors.
Multiple sequence alignment of ASTH1I, ASTH1J, and other ETS-domain proteins detected a second, N-terminal domain shared by ASTH1I, ASTH1J and some, but not all, ETS-domain proteins. Conservation of this motif have been observed (Tei et al. (1992) Proc. Natl. Acad. Sci. USA 89: 6856-6860), and its involvement in protein self-association have been documented for TEL, an ETS-domain protein, upon its fusion with platelet-derived growth factor .beta. receptor (Carrol et al. (1996) Proc. Natl. Acad. Sci. USA 93:14845-14850). Alignment of the N-terminal conserved domain in the ETS proteins was converted into a generalized sequence profile to scan the protein databases using the Smith-Waterman algorithm. This search revealed that the N-terminal domain in ASTH1I, ASTH1J and other ETS-domain proteins belongs to the SAM-domain family (Schultz et al. (1997) Protein Science 6:249-253). SAM domains are found in diverse developmental proteins where they are thought to mediate protein-protein interactions. Thus, both ASTH1I and ASTH1J are predicted to contain two conserved modules, the N-terminal protein interaction domain (SAM-domain) and the C-terminal DNA-binding domain (ETS-domain). The sequence segments between these two domains is predicted to have elongated, non-globular structure and may be hinges between the two functional domains in ASTH1I and ASTH1J.
The ASTH1I alt1 (SEQ ID NO:7), alt2 (SEQ ID NO:9) and alt3 (SEQ ID NO:11) forms are 265, 255 and 164 amino acids in length, respectively, and differ at their 5' ends. The ASTH1 and ASTH1J proteins show similarity to each other in the ets domain and between ASTH1J exon c and ASTH1I exon e. They are more related to each other than to other proteins. Over the ets domain they are 66% similar (ie. have amino acids with similar properties in the same positions) and 46% identical to each other. All three forms of ASTH1I have the helix turn helix motif located near the carboxy terminal end of the protein.
The alternate forms of the ASTH1I protein may differ in function in critical ways. The activity of ets transcription factors can be affected by the presence of independently folding protein structural motifs which interact with the ets protein binding domain (helix loop helix). The differing 5' ends of the ASTH1I proteins may help modulate activity of the proteins in a tissue-specific manner.
Polymorphism analysis of ASTH1I and ASTH1J
Affected and unaffected individuals from the Toronto cohort were used to determine sequence variants, as were approximately 25 controls derived from populations not selected for asthma. Affected and unaffected individuals from the Tristan da Cunha population were also chosen; the set to be assayed was also selected to represent all the major haplotypes for the ASTH1 region in that population. This ensured that all chromosome types for Tristan were included in the analysis.
Polymorphism analysis was accomplished by three techniques: comparative (heterozygote detection) sequencing, radioactive SSCP and fluorescent SSCP. Polymorphisms found by SSCP were sequenced to determine the exact sequence change involved.
PCR and sequencing primers were designed from genomic sequence flanking each exon of the coding region and 5' UTRs of ASTH1I and ASTH1J. For fluorescent SSCP, the forward and reverse PCR primers were labeled with different dyes to allow visualization of both strands of the PCR product. In general, a variant seen in one strand of the product was also apparent in the other strand. For comparative sequencing, heterozygotes were also detected in sequences from both DNA strands.
Polymorphisms associated with the ASTH1I locus are listed in Table 3. The sequence flanking each variant is shown. Polymorphisms were also deduced from comparison of sequences from multiple independent cDNA clones spanning the same region of the transcripts, and comparison with genomic DNA sequence. The polymorphisms in the long 3' UTR regions of these genes were found by this method. One polymorphism in each gene is associated with an amino acid change in the protein sequence. An alanine/valine difference in exon c of ASTH1J is a conservative amino acid change. A serine/cysteine variant in exon g of ASTH1I is not a conservative change, but would be found only in the alt3 form of the protein.
The polymorphisms in the ASTH1I and J transcribed regions were genotyped in the whole Tristan da Cunha and Toronto populations, as well as in a larger sample of non-asthma selected controls, by high throughput methods such as OLA (oligonucleotide ligation assay; Tobe et al. (1996) Nucl. Acids Res. 24:3728) or Taqman (Holland et al. (1992) Clin. Chem. 38: 462), or by PCR and restriction enzyme digestion. The population-wide data were used in a statistical analysis for significant differences in the frequencies of ASTH1I or ASTH1J alleles between asthmatics and non-asthmatics.
TABLE 3__________________________________________________________________________POLYMORPHISMS IN THE ASTH1I AND ASTH1J GENES. Polymorphism Location SequenceSEQ ASTH1I Transcribed region__________________________________________________________________________ EXON B (+)170 ACAGAATGACRTATGAAAAGT INTRON D (+)15 GTAACCAAGCKCAAGCCACCC INTRON F (+)24 AAGGAGCCCAYCTGAGTGCAG EXON G (+)62 ser.fwdarw.cys CGTTCCATCTSTGCTCTGTGC20. EXON H (+)77 AGCGCCTCGGYTGGCTGAGGG EXON A 3' UTR (+)1176 TGTATTCAAGYGCTATAACAC EXON I (+)76 CACTGAGAAGCCC/-ACAGGCCTGT EXON I (+)86 CCCACAGGCCWGTCCCTCCAA INTRON J (+)93 CGTCCATCTCYAGCTCCAGGG ASTH1J Transcribed region EXON A 5' UTR (+)38 GACTTGATAAYGCCCGTGGTG EXON A 5' UTR (+)39 ACTTGATAACRCCCGTGGTGC EXON A 5' UTR (+)99 CTCCCCTCCAWGAGCCACAGC INTRON A (+) 224/225 ATTTCCTGCATT/-GTCTGGACTT INTRON A (+)48 ATCCAAACACYTGAGTGGAAA30. EXON A3 (+)28 AGTTTCCTCARTGCGGGAGCT EXON C (+)158 GCGAGCACCTYTGCAGCATGA EXON C (+)190 ala.fwdarw.val TTCACCCGGGYGGCAGGGACG INTRON D (-)36/37 CTGGGGAAAA(GA)/TGATCGCTGAC INTRON F (-)22 GTCAATTAAAYGGCTCTCATT INTRON G (=)27 TAGATCATTCRTAACCTGCCT EXON I (3' UTR) (+)22 AAAGAGAAATWCTGGAGCGTG EXON I (3' UTR) (+)220 ATGAGGGGAAMAAGAAACTAC EXON I (3' UTR) (+)475 TTTTGTATGTKACATGATTTA EXON I (3' UTR) (+)871 AGCTTGGTTCYTTTTTGCTCC40. EXON I (3' UTR) (+)1084 TTGACACCAGRAACCCCCCAG 5' to ASTH1J CAAT box -165 AAATGAGCCARTGTTTGTAAT 5PW1J.sub.-- P01+399 ATCCATTTTGYATTCCTCATT 5PW1J.sub.-- P01+1604 CTGGAGCTCARACCAGACAGC 5PW1J.sub.-- P02+1382 GCCAGTGCAGSCATCATTACC 5PW1J.sub.-- P03+128 AGTTCAAATCRTAATTTTTAT 5PW1J.sub.-- P03+556 TCATCAGAATYTAAATCTCCC 5PW1J.sub.-- P03+712 GGAGATTCAGA/-TGAAGCAAGA 5PW1J.sub.-- P03+781 TTTTTCCACAYCCAGCCTGGC 5PW1J.sub.-- P03+791 CCCAGCCTGGYGAACCCTGGC50. 5PW1J.sub.-- P03+820 CTCTTCATCAYGGTCAAATAC 5PW1J.sub.-- P03+1530 CAACTTGCTGYCAAAGTGCTG 5PW1J.sub.-- P03+1605 TACTATGTGCYAGATACTAAG 5PW1J.sub.-- P04+542/543 ATGCCACTTTRRACAACTTGAG 5PW1J.sub.-- P04+973 CGCATGCCTGKAAAGAAGAGA 5PW1J.sub.-- P04+1079 GGATAAGCACMAGTGAGCCTG 5PW1J.sub.-- P04+1153 AAAGCCAGACRGCAACTTGTG 5PW1J.sub.-- P04+1430 TCTCAAAAAGRGTGATAGGAG 5PW1J.sub.-- P05+334 TCTGAATCCTSTCTCCTCCTT 5PW1J.sub.-- P05+749 TAGAACCAGGWTGTGGGACCA60. 5PW1J.sub.-- P05+915 TTCTTGTGTCRGGCGCAAAAC 5PW1J.sub.-- P06+529 AACCAACATGRAGAAACCCCA 5PW1J.sub.-- P06+1290 AATAAACTATRGTTCACCTAG 5PW1J.sub.-- P06+1573 ACATATTTGTRTCTCATATGA 5PW1J.sub.-- P06+1661 CAAAGCAGTTYCTAATAATCC 5PW1J.sub.-- P07+335 AGATCCTAACYGGGGCCTCCT 5PW1J.sub.-- P07+731 CTCTTTCTCTYTGCTTCCTCC 5PW1J.sub.-- P07+1024 TTAGGAATCCWCAAATATGTA 5PW1J.sub.-- P07+1610 GTCTGACTCCRCCTCCCTCAT 5PW1J.sub.-- P08+398 GAATCACATCRTGAGAAATGT70. 5PW1J.sub.-- P08+439 AATTCAATCCYTCACAGACTT 5PW1J.sub.-- P08+580 GTGTAGCCAGRGTTGCTAATT 5PW1J.sub.-- P08+762 CCTAGAAATASCCAAGGGCAC 5PW1J.sub.-- P08+952 AAATTCTCATRCCTCACCCTC 5PW1J.sub.-- P08+1172 TCCCACCCCTRTCACCTTCAT 5PW1J.sub.-- P08+1393 CCTCATTCTCRGAAGCCAACA 5PW1J.sub.-- P08+1433 GAAGAGCCGTYCAGTCCCTTT 5PW1J.sub.-- P08+1670 TCCATAGGCTYTTTATTTGGC 5PW1J.sub.-- P08+1730 TCGTTTAGTAYACAGGCTTTG 5PW1J.sub.-- P09+59 GCCTCAGTTGYCCCAGCTATA80. 5PW1J.sub.-- P09+145 AGCAAAATGCWCTATGCACTG 5PW1J.sub.-- P09+892 GTGTCCTGAC(TTGCACTCCAC)/- ACACTGCCTG 5PW1J.sub.-- P10+1070 ATCAGATAACRCCTACACTTA 5PW1J.sub.-- P10+1511 TCTCTCTTCTSCCTGCCCTGT 5PW1J.sub.-- P09+1132 TGGACACAGGKAGGGGAATAT 5PW1J.sub.-- P09+1688 TGTCACTTGCRCATACAAGGC 5PW1J.sub.-- P09+1900 ATCATCAGATYAGCCCAGAAT 5PW1J W1R1-1060 TCAACAGAGARAGTTAATGGT 5PW1J W1R1-1831 AGCAATAATGYTTCCCTTTTC 5PW1J W1R1-2355 TCTAGCTTTTYTGTGTTTTTT90. 5PW1J W1R1-3160 GATTCCTTAAYGCTTGATACT 5PW1J W1R1-3787 CCTCCTCCAGYACCAAAGTGG W1J.sub.-- CD+24 ATGGCCACAGRTCAAATCCTG W1J.sub.-- CA+564 ACTGAGTGTTYATGCCAATTT 5' to ASTH1I WI.sub.-- CL+94 GACAAGCCCTRTCTGACACAC WI.sub.-- CN+134 TGAAAAGCCTYCTTGCTGCCT WI.sub.-- CQ-28 TCCTGGAGTTYCTTTGCTCCC WI.sub.-- CQ+39 GATTCCAAATWAACTAAAGAT P14-16+191662 GACCTCAAGTCRTCCACCCGCC P14-16+192592 AACAAATACTMCCCCGCAACCC100. P14-16+192762 ATTTTTTTTTT/-AAGGAAAATA101. P14-16+195066 AAATTTCCCCMAAACAAGCAG102. P14-16+196590 GAGAAAGGGTRTGTGTGTGTG103. P14-16+196617 GTGTGTGTGTGT-/GTGTATGTGCGCGTG104. P14-16+196902 ATCGGGAACCYCATACCCCAA105. P14-16+198040 TTTGTTTCGCMATGAGGTACG106. P14-16+198240 TGAGGGTGTTSTGGGCTGGAC107. P14-16+198840 TCTTCATTGGYATCTGAATGT108. P14-16+200120 GCGAGCACCTYTGCAGCATGA109. P14-16+200617 AACCCCCCCCMCACACACACA110. J5-16+4454 TCAGTGCTCTSTAATCAGTCA111. J5-16+4825 TCTTTGTGAAA-/(GA)AATTAGTCTG*112. J5-16+5426 GCTGCCCTGASAGCTGGGCCA113. J5-16+5623 CCTTCTGATCYTTGTTTGCTG114. J5-16+7386 GGAACACTGAKTCTTGATTAG115. J5-16+7904 TAGGCTTCTCYTGATAATTGA116. J5-16+8055 TCTTAAAATAMTTGGCTTGTA117. J5-16+10595 TAGATCATTARTAACCTGCCT118. J5-16+11140 ATGAGGGGAAMAAGAAACTAC119. J5-16+12004 TTGACACCAGRAACCCCCCAG120. J5-16+12219 TGTTTTAAATRTTAGGGACAA121. J5-16+12303 GTAAGCATAGYAATGTAGCAG122. J5-16+13504 GGCTCTTTCTKCAACCTTTCC123. J5-16+14120 GACCCAGGTTRTGAGTTTTCC124. ASTH1I, exon B +169 GACAGAATGAYATATGAAAAG125. ASTH1I, exon I +69 TGTGTGACACYGAGAAGCCCA126. ASTH1J, exon C +56 AGTACTGGACMAAGTACCAGG127. 5' ASTH1J, WI.sub.-- Cg -9 CCTGGGAGCARGTATTGCATT ASTH1J Intron A128. WIJ.sub.-- Ia01 +39 AGATTTGAGGYCTCAGGTCCC129. WIJ.sub.-- Ia01 +140 TGTCAATGTCRCATGATAAGC130. WIJ.sub.-- Ia01 +678 TTGCCCCAGTKTTCTCCGGGC131. WIJ.sub.-- Ia01 +855 TATGAGCAGCRTAGGGAGTGG132. WIJ.sub.-- Ia01 +929 AGTTGACTGA(AAAA)/-TAAATAAGAC133. WIJ.sub.-- Ia 03 +362 ATTCAAATAGSCTCTAGAAAC134. WIJ.sub.-- Ia 03 +918 CCCAGAATTTMATATCCATTC135. WIJ.sub.-- Ia 03 +943 TGACCCAACARAAACTCACTG136. WIJ.sub.-- Ia 03 +1569 CCAGAATATAWCATCAGCCCT137. WIJ.sub.-- Ia 03 +1580 CATCAGCCCTWCTGAGGAGAT138. WIJ.sub.-- Ia 02 +435 CCAGAACAGAYTTTATTCTGT139. WIJ.sub.-- Ia 02 +583 TTCAGCCATCYTTCCAGTTGT140. WIJ.sub.-- Ia 02 +643 TCACTAACTCWAAAACGACAT141. WIJ.sub.-- Ia 02 +648 AACTCAAAAAYGACATCCTCC142. WIJ.sub.-- Ia 02 +1048 GAACTGCACARGTTGCACACT143. WIJ.sub.-- Ia 02 +1061 TTGTTCCATGSACTACCTCCT144. WIJ.sub.-- Ia 02 +1142 ACAGCAGGCAYTCAACAAATT145. WIJ.sub.-- Ia 04 +410 TTATTTTTGGSTTTGTTTTAA146. WIJ.sub.-- Ia 04 +1056 TAGGCTGTTCYCTGCCATCAC147. WIJ.sub.-- Ia 05 +1484 GTGCTCTGGGMCACACAGCTC148. WIJ.sub.-- Ia 05 +1103 AGACCCGATARGAGCTCCTTC149. WIJ.sub.-- Ia 05 +1823 CATCTTGCGCRGTCATGTAAG150. WIJ.sub.-- Ia 05 +1852 CAGCACAGCTRTTCCCTCAAA151. WIJ.sub.-- Ia 05 +1906 TTTGGAAACAYGGTGAAGTAT152. WIJ.sub.-- Ia 05 +1913 ACACGGTGAARTATTGTCTCC153. WIJ.sub.-- Ia 06 +794 AAAAGTGGATMCTCTGCAAAC154. WIJ.sub.-- Ia 06 +814 CTTCAAATGCRGCTATTAAAG155. WIJ.sub.-- Ia 06 +1197 CCTGGGAGCAYGGTAAATCAG156. WIJ.sub.-- Ia 06 +1231 TGAAAATGTCRCTTTCTCACCT157. WIJ.sub.-- Ia 06 +1256 CCTGATATTTRCCAACAAGAA158. WIJ.sub.-- Ia 06 +1535 AAAGGGTTAGYTTGTCCCCTT159. WI.sub.-- Caa +163 TGAAAATAAAASACAATTTTTT__________________________________________________________________________ The sequences are listed with the variant residues represented by the appropriate single letter designation, i.e. A or G is shown by "R". The variant residues are underlined. Where the polymorphism is a deletion, th underlined residues are underlined, and the alternative form shownas a "-". .sup.a Where intron `a` is the intron 3' to exon `a`, etc. .sup.b Position numbers correspond to the position within the intron or exon, with nucleotide +1 being the 5most base of the exon or the intron. Alternatively, negative numbers denote the number of bases from the 3' en of an intron. .sup.c Position in cDNA = position # for the exon a form of ASTH1J or the exon i form of ASTH1I. .sup.d Exonic sequences are uppercase, intronic sequences lower case. UTR = untranslated region. N/A = not applicable.
Cross-species sequence conservation
Cross-species sequence conservation can reveal the presence of functionally important areas of sequence within a larger region. Approximately 90 kb of sequence lie between ASTH1I and ASTH1J, which are transcribed in opposite directions (FIG. 1). The transcriptional orientation of these genes may allow coordinate regulation of their expression. The expression patterns of these genes are similar but not identical. Sequences found 5' to genes are critical for expression. To search for regulatory or other important regions, the genomic sequence between ASTH1I and ASTH1J, was examined and plasmid clones derived from genomic sequencing experiments chosen for cross-species hybridization experiments. The criterion for probe choice was a lack of repeat elements such as Alu or LINEs. Inserts from these clones were used as probes on Southern blots of EcoRI-digested human, mouse and pig or cow genomic DNA. Probes that produced discrete bands in more than one species were considered conserved.
Conserved probes clustered in four locations. One region was located 5' to ASTH1I and spanned exon j of this gene. A second conserved region was located 5' to ASTH1J, spanning approximately 10 kb and beginning 6 kb 5' to ASTH1J exon a (and is within SEQ ID NO:1). Two other clusters of conserved probes were noted in the region between ASTH1I and J. They are approximately 10 and 6 kb in length.
Promoters, enhancers and other important control regions are generally found near the 5' ends of genes or within introns. Methods of identifying and characterizing such regions include: luciferase assays, chloramphenicol acetyl transferase (CAT) assays, gel shift assays, DNAsel protection assays (footprinting), methylation interference assays, DNAsel hypersensitivity assays to detect functionally relevant chromatin-ree regions, other types of chemical protection assays, transgenic mice with putative promoter regions linked to a reporter gene such as .beta.-galactosidase, etc. Such studies define the promoters and other critical control regions of ASTH1I and ASTH1J and establish the functional significance of the evolutionarily conserved sequences between these genes.
Discussion
The ASTH1 locus is associated with asthma and bronchial hyperreactivity. ASTH1I and ASTH1J are transcription factors expressed in trachea, lung and several other tissues. The main site of their effect upon asthma may therefore be in trachea and lung tissues. Since ets family genes are transcription factors, a function for ASTH1I and ASTH1J is activation of transcription of particular sets of genes within cells of the trachea and lung. Cytokines are extracellular signalling proteins important in inflammation, a common feature of asthma. Several ets family transcription factors activate expression of cytokines or cytokine receptors in response to their own activation by upstream signals. ELF, for example, activates IL-2, IL-3, IL-2 receptor .alpha. and GM-CSF, factors involved in signaling between cell types important in asthma. NET activates transcription of the IL-1 receptor antagonist gene. ETS1 activates the T cell receptor .alpha. gene, which has been linked to atopic asthma in some families (Moffatt et al. (1994) supra.)
Activation of genes involved in inflammation by other members of the ets family suggest that the effect of these ASTH1 genes on development of asthma is exerted through influencing cytokine or receptor expression in trachea and/or lung. Cytokines are produced by structural cells within the airway, including epithelial cells, endothelial cells and fibroblasts, bringing about recruitment of inflammatory cells into the airway.
A model for the role of ASTH1I and ASTH1J in asthma that is consistent with the phenotype linked to ASTH1, the expression pattern of these genes, the nature of the ASTH1I/J genes, and the known function of similar genes is that aberrant function of ASTH1I and/or ASTH1J in trachea or lung leads to altered expression of factors involved in the inflammatory process, leading to chronic inflammation and asthma.
Functional analysis of a ASTH1J promoter sequence variant and location of the ASTH1J promoter
Primer extension analyses performed using total RNA isolated from both bronchial and prostate epithelial cells have revealed one major and five minor transcription start sites for ASTH1J. The major site accounts for more than 90% of ASTH1J gene transcriptional initiation. None of these sites are found when the primer extension analysis is performed using mRNA isolated from human lung fibroblasts that do not express ASTH1J.
Identification of the ASTH1J transcriptional start site has allowed the localization of a putative TATA box (TTTAAAA) between positions -24 and -30 (24 to 30 bp 5' to the transcription start site). Although the sequence is not that of a typical TATA box, it conforms to the consensus sequence (TATAMA) for TATA box protein binding as compared with 389 TATA elements (Transfac database: http://transfac.gbf-braunschweig.de/, ID: V$TATA.sub.-- 01).
Analysis of the CAAT box "G" polymorphism by gel shift assay
Binding of nuclear proteins to a polymorphism in the GCCAAT motif (GCCAAT or GCCAGT) found at position -140 (140 bp 5' to the transcription start of ASTH1J as defined by primer extension experiments, previously referred to as "-165 bp"), has been assessed using electrophoretic mobility shift assays. These experiments clearly showed a remarkable difference when binding of nuclear proteins to radioactively-labelled double stranded oligonucleotides containing the normal "A" vs the mutant "G" nucleotide was examined. A specific set of nuclear proteins was able to bind to the normal oligonucleotide, but did not bind to the "G" oligonucleotide. The specificity of the DNA binding complexes was further addressed by competition with either normal or mutant unlabeled oligonucleotides. Addition of increasing amounts of normal unlabeled oligonucleotide effectively competed binding of nuclear proteins to the labeled normal oligonucleotide, while the addition of increasing amounts of unlabelled "G" oligonucleotide did not.
The GCCAAT cis-element is found in many promoters at various locations relative to genes, as well as in distal enhancer elements. There is no known correlation between location of these elements and activity. Both positive and negative regulatory trans-acting factors are known to bind this class of cis element. These factors can be grouped into the NF-1 and C/EBP families.
The nuclear factor-1 (NF-1) family of transcription factors comprises a large group of eukaryotic DNA binding proteins. Diversity within this gene family is contributed by multiple genes (including: NF-1A, NF-1B, NF-1C and NF-1X), differential splicing and heterodimerization.
Transcription factor C/EBP (CCAAT-enhancer binding protein) is a heat stable, sequence-specific DNA binding protein first purified from rat liver nuclei. C/EBP binds DNA through a bipartite structural motif and appears to function exclusively in terminally differentiated, growth arrested cells. C/EBPa was originally described as NF-IL-6; it is induced by IL-6 in liver, where it is the major C/EBP binding component. Three more recently described members of this gene family, designated CRP 1, C/EBP .beta. and C/EBP .delta., exhibit similar DNA binding specificities and affinities to C/EBP .alpha.. Furthermore, C/EBP .beta. and C/EBP .delta. readily form heterodimers with each other as well as with C/EBP .alpha..
Members of the C/EBP family of transcription factors, but not members of the NF-1 family, bind to the ASTH1J promoter region, as determined by the use of commercially available antibodies (Santa Cruz Biotechnologies, Santa Cruz, Calif.) that recognize all NF-1 and C/EBP family members known to date, in electrophoretic mobility shift assays.
Fabricating a DNA array of polymorphic sequences
DNA array: is made by spotting DNA fragments onto glass microscope slides which are pretreated with poly-L-lysine. Spotting onto the array is accomplished by a robotic arrayer. The DNA is cross-linked to the glass by ultraviolet irradiation, and the free poly-L-lysine groups are blocked by treatment with 0.05% succinic anhydride, 50% 1-methyl-2-pyrrolidinone and 50% borate buffer.
The spots on the array are oligonucleotides synthesized on an ABI automated synthesizer. Each spot is one of the alternative polymorphic sequences indicated in Tables 3 to 8. For each pair of polymorphisms, both forms are included. Subsets include (1) the ASTH1J polymorphisms of Table 3, (2) the ASTH1I polymorphisms of Table 3; and (3) the polymorphisms of Table 4. Some internal standards and negative control spots including non-polymorphic coding region sequences and bacterial controls are included.
Genomic DNA from patient samples is isolated, amplified and subsequently labeled with fluorescent nucleotides as follows: isolated DNA is added to a standard PCR reaction containing primers (100 pmoles each), 250 uM nucleotides, and 5 Units of Taq polymerase (Perkin Elmer). In addition, fluorescent nucleotides (Cy3-dUTP (green fluorescence) or Cy5-dUTP (red fluorescence), sold by Amersham) are added to a final concentration of 60 uM. The reaction is carried out in a Perkin Elmer thermocycler (PE9600) for 30 cycles using the following cycle profile: 92.degree. C. for 30 seconds, 58.degree. C. for 30 seconds, and 72.degree. C. for 2 minutes. Unincorporated fluorescent nucleotides are removed by size exclusion chromatography (Microcon-30 concentration devices, sold by Amicon).
Buffer replacement, removal of small nucleotides and primers and sample concentration is accomplished by ultrafiltration over an Amicon microconcentrator-30 (mwco=30,000 Da) with three changes of 0.45 ml TE. The sample is reduced to 5 .mu.l and supplemented with 1.4 .mu.l 20.times. SSC and 5 .mu.g yeast tRNA. Particles are removed from this mixture by filtration through a pre-wetted 0.45.mu. microspin filter (Ultrafree-MC, Millipore, Bedford, Mass.). SDS is added to a 0.28% final concentration. The fluorescently-labeled cDNA mixture is then heated to 98.degree. C. for 2 min., quickly cooled and applied to the DNA array on a microscope slide. Hybridization proceeds under a coverslip, and the slide assembly is kept in a humidified chamber at 65.degree. C. for 15 hours.
The slide is washed briefly in 1.times. SSC and 0.03% SDS, followed by a wash in 0.06% SSC. The slide is kept in a humidified chamber until fluorescence scanning was done.
Fluorescence scanning and data acquisition. Fluorescence scanning is set for 20 microns/pixel and two readings are taken per pixel. Data for channel 1 is set to collect fluorescence from Cy3 with excitation at 520 nm and emission at 550-600 nm. Channel 2 collects signals excited at 647 nm and emitted at 660-705 nm, appropriate for Cy5. No neutral density filters are applied to the signal from either channel, and the photomultiplier tube gain is set to 5. Fine adjustments are then made to the photomultiplier gain so that signals collected from the two spots are equivalent.
Construction of an asth1J Transgenic Mouse
Isolation of mouse asth1-J genomic fragment:
Phage MW1-J was isolated by screening a mouse 129Sv genomic phage library (Stratagene) with the 443 bp BamHI-SmaI fragment from the 5' region of the human asth1-J cDNA clone PA1001A as probe. The 23 kb insert in MW1-J was sequenced.
Assembly of asth1-Jexb targeting construct:
A 2.65 kb Sacd fragment (bp7115-bp9765) from MW1-J was isolated, cloned into the SacI site of pUC19, isolated from the resultant plasmid as an EcoRI-XbaI fragment, inserted into the EcoRI-XbaI sites of pBluescriptII KS+ (Stratagene), and the 2.5 kb XhoI-MluI fragment isolated. A 5.4 kb HindIII fragment (bp11515-bp16909) was isolated from MW1-J, inserted into the HindIII site of pBluescriptII KS+, reisolated as a XhoI-NotI fragment, inserted into the XhoI-NotI sites of PPNT, and the 9.5 kb XhoI-MluI fragment isolated. The two XhoI-MluI fragments were ligated together to produce the final targeting construct plasmid, asth1exb. Asth1exb was linearized by digestion with NotI and purified by CsCl banding.
Identification of targeted ES clones:
Approximately 10 million RW4 ES cells (Genome Systems) were electroporated with 20 .mu.g of linearized asth1exb and grown on mitomycin C inactivated MEFs (Mouse Embryo Fibroblasts) in ES cell medium (DMEM+15% fetal bovine serum+1000U/ml LIF (Life Technologies)) and 400 .mu.g/ml G418. After 24-48 hrs, the cells were refed with ES cell medium. After 7-10 days in selection culture approximately 200 colonies were picked, trypsinized, grown in 96 well microtiter plates, and expanded in duplicate 24 well microtiter plates. Cells from one set of plates were trypsinized, resuspended in freezing medium (Joyner, A., ed., Gene Targeting, A Practical Approach. 1993. Oxford University Press), and stored at -85 C. Genomic DNA was isolated from the other set of plates by standard methods (Joyner, supra.) Approximately 10 .mu.g of genomic DNA per clone were digested with NdeI and screened by southern blotting using a 100 bp fragment (bp6164-bp6260) as probe. A banding pattern consistent with targeted replacement by homologous recombination at the asth1-J locus was detected in 10 of 113 clones screened.
Production of asth1-J knockout mice:
Two of the targeted clones, cl#117 and cl#58, were expanded and injected into C57BL/6 blastocysts according to standard methods (Joyner, supra). High percentage male chimeric founder mice (as ascertained by extent of agouti coat color contribution) were bred to A/J and C57BL/6 female mice. Germline transmission was ascertained by chinchilla or albino coat color offspring from A/J outcrosses and by agouti coat color offsprint from C57BL/6 outcrosses. The NdeI southern blot assay employed for ES cell screening was used to identify germline offspring carrying the targeted allele of Asth1-J. Germline offspring from both A/J and C57BL/6 outcrosses were identified and bred with A/J or C57BL/6 mates respectively.
Mice heterozygous for the Asth1-J targeted allele are interbred to obtain mice homozygous for the asth1-J targeted allele. Homozygotes are identified by NdeI Southern blot screening described above. The germline offspring of the chimeric founders are 50% A/J or C57BL6 and 50% 129SvJ in genetic background. Subsequent generations of backcrossing with wild type A/J or C57BL/6 mates will result in halving of the 129SvJ contribution to the background. The percentage A/J or C57BL/6 background is calculated for each homozygous mouse from its breeding history.
Molecular and cellular analysis of homozygous mice
Various tissues of homozygotes, heterozygotes and wild type littermates at various stages of development from embryonic stages to mature adults are isolated and processed to obtain RNA and protein. Northern and western expression analyses as well as in situ hybridizations and immunohistochemical analyses are performed using cDNA probes and polyclonal and/or monoclonal antibodies specific for asth1-J protein.
Phenotypic analysis of homozygous mice:
A/J, C57BL/6, wild type, heterozygous and homozygous mice in both A/J and C57BL/6 backgrounds at varying stages of development are assessed for gross pathology and overt behavioral phenotypic differences such as weight, breeding performance, alertness and activity level, etc.
Metacholine challenge tests are performed according to published protocols (De Sanctis et al. (1995). Quantitative Locus Analysis of Airway Hyperresponsiveness in A/J and C57BL/6J mice. Nat. Genet. 11:150-154.).
Targeting at asth1-J exon C:
Assembly of exon C targeting construct:
A 3.2 kb HindIII-XbaI fragment (bp11515-bp14752) from MW1-J was isolated, cloned into the HindIII-XbaI site of pUC19, isolated from the resultant plasmid as a KpnI-XbaI fragment, inserted into the KpnI-XbaI sites of pBluescriptII KS+ (Stratagene), and the 4.5 kb RsrII-MluI fragment isolated. A 3.4 kb HindIII fragment (bp17217-bp20622) was isolated from MW1-J, inserted into the HindIII site of pBluescriptII KS+, reisolated as a XhoI-NotI fragment, inserted into the XhoI-NotI sites of pPNT, and the 9.5 kb RsrII-MluI fragment isolated. The two RsrII-MluI fragments were ligated together to produce the final targeting construct plasmid, Asth1exc. Asth1exc was linearized by digestion with NotI and purified by CsCI banding.
Identification of targeted ES clones:
Approximately 10 million RW4 ES cells (Genome Systems) were electroporated with 20.mu.g of linearized asth1exc and grown on mitomycin C inactivated MEFs (Mouse Embryo Fibroblasts) in ES cell medium (DMEM+15% fetal bovine serum+1000U/ml LIF (Life Technologies)) and 400 .mu.g/mI G418. After 24-48 hrs, the cells were refed with ES cell medium. After 7-10 days in selection culture approximately 200 colonies were picked, trypsinized, grown in 96 well microtiter plates, and expanded in duplicate 24 well microtiter plates. Cells from one set of plates were trypsinized, resuspended in freezing medium (Joyner, supra), and stored at -85 C. Genomic DNA was isolated from the other set of plates by standard methods (Joyner, supra). Approximately 10 .mu.g of genomic DNA per clone were digested with Ncol and screened by southern blotting using a 518 bp fragment (bp8043-bp8560) as probe. A banding pattern consistent with targeted replacement by homologous recombination at the Asth1-J locus was detected in 3 of 46 clones screened.
Targeted clones are injected into blastocysts and high percentage chimeras bred to A/J and C57BL/6 mates analogously to that done for asth1-Jexb knockout mice. Heterozygote, homozygote and wild type littermates are obtained and analyzed analogously to that done for asth1-Jexb knockout mice.
The data presented above demonstrate that ASTH1I and ASTH1J are novel human genes linked to a history of clinical asthma and bronchial hyperreactivity in two asthma cohorts, the population of Tristan da Cunha and a set of Canadian asthma families. A TDT curve in the ASTH1 region indicates that ASTH1I and ASTH1J are located in the region most highly associated with disease. The genes have been characterized and their genetic structure determined. Full length cDNA sequence for three isoforms of ASTH1I and three isoforms of ASTH1J are reported. The genes are novel members of the ets family of transcription factors, which have been implicated in the activation of a variety of genes including the TCRa gene and cytokine genes known to be important in the aetiology of asthma. Polymorphisms in the ASTH1I and ASTH1J genes are described. These polymorphisms are useful in the presymptomatic diagnosis of asthma susceptibility, and in the confirmation of diagnosis of asthma and of asthma subtypes.
All publications and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.
Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be readily apparent to those of ordinary skill in the art in light of the teachings of this invention that certain changes and modifications may be made thereto without departing from the spirit or scope of the appended claims.
__________________________________________________________________________# SEQUENCE LISTING- (1) GENERAL INFORMATION:- (iii) NUMBER OF SEQUENCES: 339- (2) INFORMATION FOR SEQ ID NO:1:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 72928 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Genomic DNA- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:- GCACTTTTTG GGGAAGGTGG AAGAATAAAA GTAAGGGAGG TGTGCTGAGA CT - #TCAATTTT 60- AATATCTTAT TTCTTAGGTT GAGTGTTACA CAGGCATTTG TAATCATATA TA - #CTTTTGTA120- CACTTGAAAT ATATATATTT GTGTGTGTGT GTGTGTGTGT GTCAGAGTCT CA - #CTCTGTCT180- CCCAGGCTGG AGTGCAGTGG TGTGATCTTG GCTCATTGCA ACCTCCACCT CC - #CAGGTTCA240- AGAGCTTTTT GTGCCTCCAT CTCCTGAGTA GCTGAGACTA CAGGCAAGCA CC - #ACCACACC300- GGCTAATTTT TGTATTTTTA GTAGAGATGG GGTTTCACCA TGTTGCCCAG GC - #TGGTCTCA360- AATTCCTGGC CTCAAGTGAT CCAGTCACCT TGGCCTCCCA AAGTGCTGGA AT - #TACAGGCG420- TGAGCCACCA TGCCCGGTCT GAAATATTTC AAAATGTAAA AAAGCTAAAC CC - #AAATCCAG480- ATGTCTACTT TCAAGGTGCT CACAGGTCAG ATCTAGGATT ATTGCTACTA AC - #TGATATTT540- ATTATCCCAG CACCAGCATG TTTGGCTGTG TGTCATGGGT AAGTTACTCA CC - #TTCTCTGC600- GACAGTGTCA TCATTGTAAA ATAGGGATAA AAGAGTTTAG ACCTTGCAGA GT - #CCTTCAGA660- TTAAAGGAGA TAATCAGTAC GTGGCACTGA GTACCTGCAA TATATTAAGT GG - #TGTGTGCT720- CAGAGATATG ATCACATACA GTATCTTGGA TCTGCCCAGC AACTCTATGA AG - #ATGAGGAA780- ACAGACTCAG GCAGGTCAGA GCCAGAACAT AATGTTTCTG GAATTTGAAC GT - #AAACGTTC840- CCCTTTCTCT TATCCAGGCT GAGTGCTAAA GGAATTGTAA AAATGGAATT TG - #CCTGTTGC900- CTGCATCTCC CTCTCTTTTT CTTCCTCTGT GTCCTCTGAA TATCTAGCAC CA - #GTGGGACT960- TTACAGTGTT GGCCTCAATG CTGTAGGGTG CTGTGTGCAC ACTTGTCTTC AG - #CTCCCTGA1020- GTTAGCAGAG CATTGCCCCA ACTCTGCCCT CTGGCCAGCT CATGTGCCTT AC - #AACTTTCT1080- GTTGCCAGAA GAGAGCCCTG CTCATTCTCT AGACTCAACC AACAAAAGCT GC - #CTACCATT1140- TTCAGAATGC CAGTGGGCAG TGAGAAGTGC AGAGCTTGTG TCCTGAGCTT GG - #CAGCCATC1200- TTGCTTGGTG TTAACAAAGA GTAATTAAGT GATCTCATAA AACTCAGTGG TG - #GAGGTTGT1260- GGTTCAGAGC AAGCTGGGTC AATGCCAAGG CTACTTTGGC TTCATCTGGT CC - #ATAGCCCC1320- ACATTTCTCT TCTGATGGTT CAGTTCCGGG AATGAGAACC AGTCTGAGTG TA - #AGAAGACT1380- TGGGTTTGAA TCTGTCTCCT CCAATCACTA GCTGACCTTA GAAAAGTGAC TT - #AACCTCCC1440- GAGCTGCTAT TTCCTCATCT TAAATGGTGA TAGTAATCTT TCCTTACCTT AA - #GGTTGTTG1500- AGCAGCTTAA ATAATATAAT GAGTTGAAAG CTTTTTGTAT GATCTGTTAT TA - #GGAGTCCA1560- GATAGTGTTT TATAAACAAG AGGATAAAAA AAAAAAAAAA AAAAAAAACA GG - #ATTCTGAA1620- GGCTGGACTC ATTGCATTCC TTGCAAACTA CCCACTGAGC CCCAACTCTT CC - #GTCAGCTC1680- AAAGTCACTT CTCAGAGCAA ACCAGATTGT CCTGAACCCA GCACTTGCCA AC - #ATCTCCTC1740- CTCTTCCCTG ATGAAAACTC TGGGCTGGAG TTGTGGTGGG TGAGGGGAAG GC - #AGGATAAA1800- TCAAAAATTG ATGTTTTAAG AAAACTATGG TATTCTTGGA TGCAAAGGCA TG - #AGAATGAT1860- ACCTTAGACT TTGGGGCTTG GGGAAAAGGG TGGGGGGTGG CGAGGGATAA AA - #GACTACAC1920- ATTGGGTTTA GTGGACACTG CTCGGGTTAT GGGTGCACCA AAATCTCAGA AA - #TCACCACT1980- AAAGAACTGA TTCAGGTAAC CAAACACCAC CTGTTCCCCA AAAACCTATT GA - #AATAAAAA2040- CAGAAAATTA AAAAAAAGAA AACCTATGGT ATTCTTGGAA GAAGCACAGT GG - #TGAAGTGG2100- AGTAGACACA GATGTGGAAG TGATGTGAAC TTTGGTAAGT TGCTGAGCCT CT - #GAGGATGA2160- TTTCCCTCAT CTGTCAATCA GGGAACAAAA TCCCTTACTT GTACAATGAG TA - #TTATAAAG2220- ATCAATTCAG ATGACGCATG TAAAGATGCA ATGTGGGACT GGTAGGTAGT AA - #GCATCCCA2280- TAAATGGCAG CTATTAATAA GTAATAATCA CCGAGTGGTG GGCTGCCTTT CA - #TGAAAACA2340- TTCCCAGCAA GCTGCTCTTC TGTCGGCTCA AAGTCACTTC TCAGAGTAAA TG - #AGATTGGC2400- CAGTTCTTTC TTTCCAAGGC TTTTCTGGAT ATTCATTTGT CCCAGATTTC TC - #CTGTATAC2460- AAAGCTCAGG AGTGAGGACC CCCACAGTGG GGCTTGCACA AGGATAGCCT TG - #GGGGGCTT2520- TTTCTAAGAG CTATGACTTT GAATGCTCTC TTCATCGATG CTGACAGATG AG - #GGCTGATG2580- GAAGTGGTCA TGTTTTAAAA TGTCTGATGT CCAGAAACAC AGAGATGTGT AC - #GCAAAACA2640- TTCATTCATT CAAGATGGAA TTAGTGCCCC AGACACAGAG GCAGGGGATA AA - #TAGCAAAC2700- AAGGCTTGAT TCCTGCCTTC ATAGAGCTTA CTGTCTTGTA GGGGAAACAT GA - #GTAAATTC2760- AGCAGAGTAA GGGCTCTAAT TGGGTAAATG GGGGCTAGGC TGCCTGTGTC CT - #TGGGGTGG2820- TGGGAAGGCT GCTGATCTGG GGTGCCAGAA GACCTGAGTT TTGATGCAGG CT - #CTGTGACT2880- TTGAGCAGGT CGTTTCCAAC TTCTGAGCTT CCATTTCCCT AGCTGAAAAT GG - #GGGCTTGC2940- CATACTCGAT GCTGTACTCT ATGAGTCTTT GCAGCTCTGT CATCTTTTTT TC - #TTTTGGTC3000- ACTCAGAGAC TCCAGGATTG GGAGAACAAC CTGCATTCTG ATTTAAAGTG TG - #AATCTAAT3060- AATTTCAAAA AGAAAGGGAC TAAAAGGGAC AAACTTGTTT CTGTTTATTT TC - #CATCCTTC3120- TTTGGGGAAG TGTAACATTT GAAATCAAAT TCTCATTGGC TTAGCCAATG TG - #TAGACTTC3180- GAGGGGAAAT TCTCACTGCC CAGAGAAGTG ACTAAAAATG ACCATTACAG CC - #AAAAAGAG3240- AAGTTTTTTT TTTTTTAAAA TCTGTGCTCT ACAGATGGAT GAAGTGCTGC TG - #CACATGGA3300- CAGAGTGGAT CTGGACATTC TGCATGAGCC CAGGGATCCT GAGAATGGAT TG - #GCTGAGCA3360- TAGACAGGGT GACCTATCGA TGTTCACTGT GGTCCTGATC TATGTGGCCT CT - #TCCTAAGG3420- GAAGATTTTT CTTAAGGTTG TTTCCTTTCT CAGCAGATAT TTGTGAAGAA AC - #TGTATCTG3480- TAGTCTCATT TTGTCCTTAT AATGACCCTG ATGGATGGGA GGTAGAGGGA TG - #ATGATCAG3540- TAAGAGCTGG GAAAGCACCA GGAACTAGCA AGAGCAGGAC ACCTTTTCCA CC - #ACTAGGTA3600- AATGGACCTA GTGACTGCTG GCACCGTGGG TGAGGGGACT GCCTGGCAGG AG - #CTGTGGCC3660- GTAGCTAGGG GATTACAGCT ACGGCCACAA CTCTGGCCCT GTACGGAGGG AG - #TGGGGGAA3720- ATAAAGAGTT CATATCACTC CCCTCTTTCC CTGGAGTCTC CTGCTGGTAC CT - #TGCATTGG3780- CTGAGTCTAA CTGGAAGCCA GAGGGCAAAG GAGGTACCCT TTCCAGCTCT GC - #AATTCTCT3840- TCAGACAGGG CTGGGATTTC TGGAGAGAAT TTGCAGAATC AGAAAGCAGA GC - #TTTCCAAT3900- CAATGCCAAG CAAGAGACTC TGCAGACTCT CATAGCCTTG GGACCTGAGA AA - #CCAGGTAT3960- CCAGTGAGCA GTCACTTAAG CCTGTTCACC TGGCCCTCTC TTACTTTCTC TC - #CTATAGCA4020- GCAGCAAAGG AGCGATGGGC CGAAGGGACT TGCTGGGTAG AAGTGGACCC AC - #ATTCTAAA4080- AAGGAATGGA AGAGAAACCT GATTTCTTTG ACTCGCCCTG TCCCTGAAGA TG - #AGGGGCAG4140- GCACAGACCA GCCCTCTCCA GAAAGACAAA TATATTCTTC CATTCATGGG AG - #GGGTAGTA4200- GAGACTAACA TTTGTTAAGT ATCTATTACA TGGGGGGTAT GGAGGTAGGC CC - #TTTGTGTG4260- TGTTGCCTCT TTTAATCCTT TGGTGATCAA CTCATGAAAA TAAACAGCTC CA - #GAGCCAGC4320- TGTCTTTGGA GGGTGTAGGC AGGCCCGGCT CTGGGAAACC TGGTGACACT GA - #CCTAGTTT4380- GACTTCCAAA TCTTCTCTCT TCTTCGATTC TGGTGAGCCC CACTCTAGCC CC - #ATAGTATG4440- TATGGCCAAG CACCCAGATA CTGCTTCCAT CAGGAGGAAA TAACATACCT GA - #TGAATTTC4500- TTCACTCAAG GTGTTAGGAG CTTAATGTGT TTCCCCCGCC CCCCGCACCA AG - #AGAATTTG4560- TGTTTTCCAA GACAGTCAGA GAGTGGGTGG TGCTGAACTC AAAGGAGTGA AT - #CACTAATA4620- GTGGAATCCC AGGCATTCAG GGAGGTCCTA TTTCTGGGGT GGGTTCCTTC CT - #GACACTTC4680- ATTTTCTACA AAGGTGGCAG CCACCTATTG TCTCCAGAAA GGAGGCTGTC CC - #TGTGGGTG4740- TGGTGACGGT GGGAAAGGAG AGGCACCTGC AGGCTGAAGC CAAGATCACC TG - #ATTTTCAA4800- AACCAAATCT GTCCCTACAA AGGAGAAGTG GCTTAAAAAT CCACACAGCC TC - #CCGAGTGG4860- AGGGAAGAAT TCCCTCTCCT CTCTGGAACA GGGTTCCCTT CACCCAGAAC AC - #GGTGCTGT4920- TGTTATGCAA TGTCCCTGTT GGCAAAGATA TTTGAGCCCC TTGTTTTCAG GT - #CTGTGTCA4980- TTTCCAAGAA AGAGCTGTGG CCTTTGAGTA GGACTGGGCT CCTGAATAGG GT - #CCCTGGTG5040- CCAAATGAGG GAGCCAAGAA AAGGCAGAGA AGAGGAAAGT CCTGACTTTT AC - #ATGAAGAT5100- GAGACAGCCA GCCCTGTGGC AGCCAGATGG CAGTCCTGTT GCTCTGTAGT GG - #CCTTGGGG5160- TCAGACTAGG GGCAGAGCTG GGCTGAAGGC AGGAAGGCCA GGACAAGACA GG - #TGAGAAGG5220- GCAAAGTCTC CTGTAACCTG GTGAGAAAAT GTGGGCTAAG CCATTCTCAT CT - #GGAGCTGA5280- AGGCTTGGTG GAGAATGGCC CTCAACATTC AAGTTCACAC CCATGGATTT AT - #AAAAGGCA5340- GGGCTGGGGG GAAAGGTTTT TCCCATTATA CTTAATAACA TTATCAACAA CA - #ATAATCAC5400- TACTATCATT TATTGAGCAT TGACTCAAAA GACAGTCCTT TTATGAAAAT TA - #TTTACTTA5460- AATCCTTACA AAGCTTCTAT TCATTCACCC AACACATATT TATTGAGTTC CT - #ACTATGAG5520- CCAGGCATTA TTCTAGGTGC TTAATTTAGA TCAAGGGACA AGACAGACAA AA - #TCCCTGTT5580- CTGGTGGCAG GGCTACTACA TGCAATTAAC AGCACACAAC TCTAGGGGGA GC - #CACATACA5640- TGGGCCACCT TATGAATGGT GTGCCCTGAG GTTAAGCATC CTGGCAGCCC CT - #TTCTGTGA5700- CATTTGCATT CTAGTGAAGG GAGTCTAATA CCAATGAAGT AGATGTCATT AT - #CCCCTGAC5760- TACAGTTTAG GAAACAGAGA CACATAGGAA TTAAGTAACT TGCTGAGTTT TT - #CAGCCAAA5820- AATGACTGAC CCATGATTTA TACTGAAGTC AGTCCTTGCA ATTCACCTGT GC - #CACGTACT5880- TGCCTTTCTC TCCCTGGTGG GCACAGGGAA GAGGGAGTAG CCAGGCTGGC CA - #GATGAGTG5940- CTGGGCTGGC TGGCCCAGTA GAGGCACCAT GTCCTGACTG GGTGGACAAA GA - #CTGGGTAG6000- GAGGTAACAG AGAATCCCTT GGTGAGTCTA ACTTAGCTAT AAGAAGGCTT GC - #TGAGAGCA6060- GCTGCCTCCA TGCAGAGGGT GGGGTGACCG GCCTTTAATC CTTCCCAGCT GA - #GGATTTAG6120- TCAAAGAAGC TTGTCTCTGG GGATAGCCTA TGGTCTTGAA GGGCCTGAGT TA - #GCTATTAG6180- TTCACCCATT TATTTAACAT TCATTCATTA TTTTTAAAAA ATTTCCTAGC TA - #TGTTTGGG6240- GGCAGAGAAG TGGGTCCAGA GACCTAGAGG TTTGCAAGGG TAGCTTCTAA AC - #TCCTTTGG6300- TTCAGAACAG AATAGAAAGT GTCCTCGGGT GACCTTGGGT CTGCTTCCCA AG - #CAAATTGA6360- GCATACGCAG CCAGAACAAA GACTGCACTC TACTCTAGTG AGCTCAGCCT GC - #TAGGCTTG6420- GATCTAGATT TTATAGCAAT AAGCTTGGAG TCTCACCTTT GGGTCAGACA GA - #GTACTACC6480- CCAGACATGA GGTAGGGAGA GCCTAGTCTA TATTCCTCTG CCTTTGTCCA AG - #CCTGCTTT6540- GTCCTTCCTC TTGACGAGGA ATAAAGATGG CTTCTGGGTG TGCATCCCCT TC - #CTTCTTCC6600- ACCTGCAGAT GTACCTGTTT GTGTGCAGTG GGCTTCTGAG TCCTGGGCAG GG - #ATGCCAGA6660- GACCGCAAGC CAGATGCTTG GGATGCCAAT CCTTGGGACT TTGAGGAGAA AG - #AGAGGTTC6720- TGAGGGGCAT CTGTCTATGG CACAGAGTCA AATGGAACAC ATGGAAGTCC CT - #TAGAAGGC6780- TGGTATCTAA GTGTTGGCCA CACAATGTCC GTTCTTCCTC CATTATTTGA AT - #TTCTCCTT6840- CTCTATCCTT CTATCTTTCT TGGCACCTTG AGCCAGGTCT GGGGTGAGAG AA - #GGGATGGT6900- GTAGGTGAAT TAGTGGTAGT TATTGGAGGA AGGCAATAAA CCCAGAAAAA GT - #GTCACGTG6960- ACTTCTTTCT TGGGCCCAGT GTGACGCTTC TAGTTAGGCT AACGTGGGTC TT - #GGGACTGT7020- TCCTGAGATT TTGTGGAAAA CTCTTTGTAT TTGTGCTGGT AACAGAAGGA AA - #CCAGAGTT7080- AGGGCTGGTG GGATGAAGCA GTGGGAACAC TGATTTCTCC TTTTTTTCAG AT - #TCAGGGAT7140- TTCTGTCAGA GACATCCGTG GGGGAGGGAT GGGATTGGGA GTGAGGAGAA TC - #CCTTTCCT7200- CTCCTCTCAC CATCTGGTGG TCCCCGTGCC CACGCACCAG CTCGTTGGAT GG - #ACATTTTG7260- ATTCCCTTAA GATGTACATT CTTCAAATCA TTGTTTGTCA TTAGCTCCCT GG - #AGAAAATG7320- GAGGGGCTGA GATATTAGTG AGAAAACATA AAGTTAATTG GGTGATGGAG AC - #TGGGAGAA7380- GGGGAATGTT AGAAGAAAGT GAGCGAGGTC TGCTAAAAGT GAACTTTATC TT - #CTTCTCAA7440- TTTTGCCTAA GACTCGTGTT GCCTGGGCAG TCTCTTTTTG GAAGAGAAAT TT - #TCATGACA7500- GTTTGGGCCA GAGATGGCAA ATAAATGCCT GACATGGTTG CTGCCAGCCC CT - #GTCTCCCG7560- ACACGTTCAC AAGGGTGCAC ACCACTTCTC CTCTCTGTGA CCATAGACTC AG - #ACCCATTG7620- CAATCCAGCA TCCTGCATGG CCCCATTGGT CAGAGTTGAC ATTTGCAATG AA - #GCTGCTTC7680- CCTATGCCTG GTTAGGCCTT TTGCTATGAA TTCTCTGGAG TTAACTATTT CC - #AAGGGGCT7740- CCAACTTATT CTTGTGATTT CCACGGGATT TGGAGCCCCA GAAGACAATC CC - #ATGTGGAT7800- TCACAAAATG CCCTCTAAAT TTGATGGCTG TCAGTGCATA CTAAGTATGA CT - #GACTCACT7860- GGTATCTGTT TCCTCCGCTG ACACAGCTGG TTCTTAGGCT CGGCAGGAGT TT - #GGGCTGAG7920- ACCTCTCATT GCTCTATATT CCCTCTGTTA CTAATGAGGT GTTGTTCCTT AA - #TTACTAGG7980- TGCTGGATAC TAGAATTGCT TTTCTTTGTT TCAGGGGATT TAGCAAAGGG CT - #TATAAATA8040- TTTCTTGTGT CTGGCATGAA CTACCTGATT TTTTTATTCT TCAGGTCACT GA - #GCTGGCAA8100- TAAAGGCAAC TCAAAGTTAG CTGGGAATCA GAATGAAGGG GGACTAGGAA AA - #GTGATGCC8160- TAGAACACCA ACAGGTGTGG GATCATCTTC ATTGTACCTT TCAGAGCCTA AG - #ATATAAGT8220- CCTCTGGATA CTCTCTGCTT GTTTATTTAA AGGAAAAAAT AATCAGAATG TG - #GGAGAAAT8280- GGGTGCTTTG GGTAATTTCA TATTCTAATT GATGAACGTG TATGAAATTA TA - #ATATTAAA8340- CCACTACTAG CCCTTGCCGT AAAAAACTAT TCCAAAATAG CTGAGTCTAA GT - #TTCCTGCC8400- TCAGTGTGTC CCACCTCTTG CGCTTGAGTC CTTAATGATC CAGAGTTTCA AG - #TCCCCAGT8460- GCCCTAATCT TGAAAAGCAG AAACTTTAGA AGTTTGCTGA AGTTTATTAG TT - #GGCTATAC8520- GATCCATCAA GAAATTGACT TTTTTGGATT AAATTCAAGA TAGTTTTTAA AA - #AATCAGAA8580- GTTTCTTTAT CATGAAAGCT AAAAAAATAA TTGAAGGTAG AGGCTAGTTG GA - #ATCCCAGT8640- TAATAGATGG ATTTCTTCCT TCTTGAAGAA ACTTGTGTCC AAGGGCAAAC TG - #AATCCTGG8700- TGGTCTATGC TGGCCACATT CAGCAAAAAA TGGCCCGAGG TTTTGATGGT TA - #TCATTCTC8760- AAAACTGTTC CTGCCAACAC ACTCTGATCC CAGGAGGTTA CCTGACCTTT AT - #AAGGCTCA8820- GTTTCCTCCC CTGTAAAATG GGCAGGGTAA TCAAGCTAGG CAAAATATTT AA - #CCTAAGTG8880- AGGAAATTGT GCTATTAGTG CCCTGAAAAA CATGTAGAAA GACATTAGAC AT - #TATTTTAT8940- TTAATATCAT GTTGAACTTA GTTTTTAAAA AGAAGACCTA TTGGATTTTC CA - #AGAACAAC9000- TAAACTGATT CCTTGTAGAC AGTTTAGAGA ATACAGAAAA TTAGAAATAG GA - #AAAAAGCA9060- AAACAAAACA AAAACCATCA AACAAAGTCT ACGCAAATAC AGTTTCTCTT AA - #CTTTTGGT9120- TTATTTCCTT CTAGTCATTT TTTAGGTGCA TTTTTAAATT GTGGTAAAAT AT - #ATGTAATG9180- TAGAATTTAC CATTGTAGCC ATTTTTAAGT GTAGAGTTCA GTGGCATTAA GT - #ACATTTAT9240- ATTGCCGTGC AACCATCACC ACCATCTATC TCCAGATTTT ATAACCCCAG AC - #TGAAACTC9300- CATATCCATT AAATGATAAC TCCCCATTCC CCTCTCCCTA CCCTGGTGAC CA - #CCATTTTA9360- CTTTCTGTTT TTATGAATTT GACTTTCTTG GCGCCTCTTA TAAGTGGGAT CA - #TTTTTAGT9420- TGTTTTTATA ATCGGTTTCC TTCCTTTAAA AATATGAATG GAGCCTAATG AA - #TATTGAAT9480- TTAGTGTACT GGTTTCTTTG AACATTTCAG CATCATAAAC ATGTTTTTGT AT - #TCTACATT9540- CTTCTTGTAT TGCTATATTC TCTATAGGAA TTTTTTTTTT TTTTTTGACA GA - #GTCTCACT9600- CTGTTGCCCA GGCTGGAGTG CAGTGGCACA ATTTCAGCTC ACTGCAACCT CC - #GCCTACTG9660- GGTTCAAATG ATTCTCCTGC CTCAGCCTCC CAAGTAGCTG GGACCAGAGG TG - #CATGCCAC9720- CATGCCTGGC TAATTTTTGC ATTTTTAGTA GAGATGGGGT TTCATCATGT TG - #GCCAGGCT9780- GGTCTTGAAC TCCTGACCTC AGGTGATCCG CCCACCTTGG CCTCCCAAAG TG - #CTGGAATT9840- ACAGGTGTGA GCCATTGGCC CCAGCCTTGA ACATCATTTT TAATGGCTGA AG - #ATTATAGA9900- ATCCAGTGGG TGTGCCATCC ATTATTAGTA TTCTGTTGTT TCCAAATATT TG - #CTGTTTTA9960- AACAGTGTTG TGAAAACATA TTTTTGTGTT GAACTTTTAT CATATTGAGA GG - #CACTTCCT10020- CTGTGCAGAA TCAAGAAATT AATTACCGGT TTATAAGGAA TGTGAACCTT TC - #AGGCTCAT10080- AATCTGTATT ACCAAATGGT TAGGAAAAAA ATGTTCAGAA GGTGCCATTC AC - #AGATGGAG10140- TGGGCTTCCA CCAGGGGCTG TGAAGCTCTA ATCTCAAAGG ATGTTGACTA CT - #GGTAGGGC10200- TGATTCAAGT ATTAGATATC TAGGAAGGGT GGGAAGGGCA GAGAAGCTTC CA - #AAATTCCT10260- ATGTAGGAGA GGCATAGGGG TGCTGATCTC TTCATAAGGG GTGACGGGAA TT - #TTCCTTGA10320- AACAGCATGT GCAGATCAAG CACTGTTCTT TCCTTTAGAG TGTGTGTTTA TT - #TGGGGCGA10380- CTTGGAGGGT TGCTAATTGA GATTATGGGG AATCTAAAGC CACACCCCAA AC - #CGCCCCTT10440- GGTTCCCCTA CCTGGGGGAG AGTTGACACT AGTCAAACCT CTCCCATCTC TG - #AGATTTTG10500- TGAATCTAGG ACTCTTGCCA CTGCACAGAC TCCAGCTGGA CCCAGGGACT CC - #AGCTTCTC10560- ACATCACCCT GGCTCATCCA TAACTCTCTT TTGTTTCATC TCAAACATCA CT - #GAGAGATG10620- GCTGCCTCTT CTCCCTTCCT AGGAAAGCCC ATGTCACAAT AAGCGCGCCT GT - #GCTTCTCA10680- TCAGTGCTTT CCTGGTAGCA CCACCTGACA AACACTGCTC GCGGCTGCCT TC - #AGCTGCTC10740- TCCAAGAAGA CGTCATAACC ACAAGAGATC TGAATCAGCC CATTTTTTCC CC - #TGTGGCAC10800- TGTGTGCTTT GGCTGCCTGG CCAGAAAGCT GGGACTGTAT TTACCTATCA TT - #TTGATACT10860- ATCTTGGGGT GTAATTGGAA TTGAGCTCTT AGTGTGGAAA TTCTTACTCA GA - #ACACAAAG10920- GATTGAAGAG TGCTTGGAGG CTGAACTCTG GAAGGACTCT TCCCTGAGGC CT - #CTTGGCAT10980- CTGGCTCTTG TTTCTTGGAG CGGTGGTATG GCCCACAGGT GGGTGTTTCC TT - #TGGGAGCA11040- ATTTCTTGCT TTTTCAGTAG CTCTGGGCTG TCATCGAGCC CACTGTTCCT TG - #TCTTCTCT11100- GCACTGTTTA GTGATGATGT AGGTGAATTG CTCCACAGTT TAATTCCAGT GG - #TAGAGCAG11160- TCACCATTTG TTGGTTTCTT TTTCTTATGG GAACTCTGGT CTGCATCTCA CT - #GTGTTTCC11220- CTTGAACGTG TCTGGGGTCC TCCAAACAGC TTCGTGTCCC TCTGAGTGCG GA - #CACTCAGA11280- TTCTAACTCA GATTCTAAGT CAATGGTCTC AGCCTTTAGA ACCGCAGGAG GC - #CAGGCGCG11340- GTGACTCACG CCTGTAATCC CAGGACTTTG GGAGGCCTAC GCGGGTGGAT CA - #CCTAAGGT11400- CAGGAGTTCG AGACCAGCCT GGCCAACACA GTGAAACCCC ATCTCTACTA AA - #AATACAAA11460- AATTAGCCAG ATGTGGTGGC ATGTGCCTGT AATCCCGGCT ACTCAGGAGG CT - #GAGGCAGA11520- GGCAGGAGAA TCGCTTGAAC ACGGGAGGTG GAGGTTGCAG TGAGCCGAGA TT - #GTGAGATT11580- GTGCCATTGC ACTCTAGCCT GGGCAACAGA GTGAGACTCC ATCTCAAAAA AA - #AAAAAAAA11640- AAAAAAAAAA AGAACCACAG GAGGGAGAGA TCATATATGA CCCCGTATGT GT - #GAAAAGTC11700- CTATCATTGC TACCCACACC AACAATATTA GTGGAAAAAT GTCTTCAAAG GA - #CATTCGAT11760- TCAATGATAC ATGAGATTTG CTTCCTTCCT TAATTTTTCC CTGTACAGCT AT - #ATAATGAT11820- TTTTTCAATC AGATCCTCTT TTCCCCCTAT TAATTGTATT TATAGGATGA GA - #TTGATTCT11880- AACACAATAG CAAATGATGT ATGCACATTT AACACATTTC GTGAAGGCAG GA - #AAGGGCAC11940- ACTATAAATT CTGTGAAATC CACATTAGAT CATGCCTCTC CTTTCTCAGT TG - #GGAGGTGG12000- GCTCTGACAG TGCTCAAGAG AAAAAAAAAT CAAGTTGTGA CAGTTTAAAA AA - #TATTTTAA12060- ATATTAAACT ATTTATTATG GAACTTAAAA CATACACAGA AGTTGGCAGA AT - #AACATCAT12120- GTACCCTAAA TATCTATCTC CAAACCTCAA CAGTGATCAA CCTGTGGTCA GT - #TCTGCCTC12180- TTCTGGTTCC CATCTGCTCT CTGACTTCAG TTTATTTTGA AGCATGTCTC AG - #ACATCTTG12240- TGACTTCAGT ATTGCACGAT GTATGTCCTA AACGTAAGCA TTCCCTTTAA AA - #CATGTATC12300- TACTTTTTAA ATGAAGAACA ATTAGGTGCA TTTTCATAAG GGTTTTAGAA AG - #GGAAGAAA12360- CTGTATTTCT TTAATTTAAA AATGTATCAG ACAACTAATC CATGTTTACT GT - #TTCTAACA12420- CGGATACCAT AATAATAGGA TCATTCTATT ATACATAGAC TAGTGAGATC AA - #TTTGTCAG12480- ATAAACTTAG AAGGGCCATT AAGAAAGTTA TGTCATAATT TTTGTCACTT GC - #TGAAACCA12540- AGACTTTAAT TCTGCAGAAC ATCATACCAG GATTCACAAT TGTATACACT GA - #TTGTGTTT12600- GTCCAGAGGT AATCTCAGAT CCACTGTATA TAATTTTCCA TTTGCCTAGC TA - #TGGGGTTG12660- GACACGTCAG TTTTTTCCAG ACCAAGGGTC TCCTAGCTTT TTTTTTATTT TT - #ATTTTTAT12720- TTTTTGAGAC AGAGTCTCTG TTGCCTGTGC TGGAGTACAC TGGTGCGATC TC - #GGCTCACT12780- GCACCCTCCA CCTCTCAGAT TCAAGTGATT CTTGTGTCTC AGCCTCCTGA GT - #TGTAGGTG12840- GGACTACAGG CACCTGCCAC CATGCCTGGA TTTTTTTTTT GTTTTTTTGT AT - #CTTTAGTA12900- GAGATGGAGT TTTGCCATGT TGGCCAGGCT GGTCTTGACC TCTTGATCTT AG - #AAGATCTG12960- CCCACCTTGG CCTCCCAAAG CTGGGATTAC AGGCATGAGC CACTGTGCCC AG - #CCTCCTAG13020- CTGTTTTGGC TGCACACTTC TATCCGTAGA TAATTAAGCA TGTACCCTTA CT - #ATTTTCCG13080- CAATATAAAT TATTTACTTA TAAATTACAT TATGTACTCT ATCACACTGG TA - #AATTAAGT13140- ATATTATAAA ACAGAAACTA AAAGTATGAA GTGAGAATTA AAAATGAATA GC - #AATTCTAA13200- TATCTTCATC TTCCCCTCAG TGGATCCTCC TGTACATACT CCAATTTGCA GA - #CCACTGGA13260- GGAGGCTGTA GGAGGCAATA TTATATCCCA GTGAGGTGTG TGGGTTGTAA AG - #CCGAACAG13320- CCTGAGTCCA CATCCCAGCT CCACCACTCC TTAGTTCTGT GACTTGGAAA CA - #TCACTTAA13380- CCTCTCTGAA TCTATCTTCT CACCTGTAAT ATGAGGGCAT TAACCCCTTA CA - #GGTTATTG13440- TAAGGTTTCT TACACTGTGC CTGTGGTAAG CATCAATACA TTTTAGCCAA TA - #ATAACAGT13500- AATGATAATA ACACATTCCT AGAGGGCTGG GATGGATCTA GATTTTTCTT CC - #CCTTTTAG13560- TGGAAGACCA CAGCATGATG CATGAATTTA CATTTCCTCA GACATTCTGG TG - #CTGATGAA13620- GGTAAAGATG GTGAGGCTGC GATGATGGTT TCAGGGATGG GTGTGTTGGG CG - #TGATGAAT13680- AGCATGATGC ATATTGTCAC TCATTTAGTT TATCTGCACT GATGATGATG CT - #GATTATAT13740- GATGACTGTT ACAGGGATGG TCACATTGTG GGTGATGAAT ATGACCAGAA AG - #GGAAGACT13800- TTCACAGTTC CTACCCGAAC TACAACATCG ATATTTTCAT TTGTCTTTCC TA - #GGAACTCT13860- TACCTTAATC ACCTGACCAA TATGCTGACG ACTAACATGT TGCGCCCTGC CT - #TTCTTCCG13920- GGCCTCTCTG CCTTGCTGAT CTGTTTTGCT GGTGTGCCCT CCACTGTGCT CT - #TGGGTCTT13980- TGTCTCTCGG TAAAGCCTAG TACTGTGGTT GCTGTACACA AAACCTGTAG AT - #GATTAAGA14040- TCTCTGTTCA CTGCAGGGCC ATTCATCTCC CAGCAACTAT TTTATCCTTA AG - #TCAAGAGA14100- CTTGCCTCTC AGCCCCTGGG GACCATGGAA AGAGTGCTAG AAACCTACAG AG - #TATGACCC14160- TTTGTAGCCT TATGCAAGAA GTGACCTGTG TCTTTCCTGT CATGAGAGAG GA - #CAGACATT14220- GCAGGAATCA AACGCATAAC ACTAGTGCAA AACTGGGGAT AATGCCCAAA CC - #TGGTTAGG14280- CAGGGGCGCC TGGAACATGC TTGTCCAGGA AATCTTCCAC TCAGTTCTGC TG - #CCTCCATG14340- TCCCAGATGA TCACAGAAGC CTCCTGAGAA GGGTTGAATC CCCCGTCGCC TG - #GGGATCCC14400- AAGAAAGCTG CAGAGGAAAG ACTTTCTCTT CCAAGATCAG AACAAAGGAC GG - #TTAGCATT14460- GTGCCCAGTA GTGCCAAAAG GTAAGGTTGG GTTAAAATAA GAATTTGCCT TA - #AGCTCTTT14520- TCCCGGGGGC TTGTTTTTTT CATTAACCTT GTTGGCTGGA CTTTAGGGAA GT - #ATGCACCA14580- TCTTCTCCAG AAGTGCTTCA GATTTTATAT TTTTAAGAAA TTCAAGAGTC TG - #AGTTAGGC14640- ACTTTAATGT AACCTCCCCA AAGCTTTTGT TCCAGGAATT GACTTGGGGA TT - #AATCTGTT14700- TAGCAAATTC TGACACAGAG GCATCTCATA ACCTTTTATT TTTTCTACAG AC - #CACATTGT14760- ATCTACCTGG GATGTTTTGA AAATGAACAG TGACACCTAA GAATGTATAC TT - #ATCTCTTC14820- ATGCCAATTC TCCAAACTGG ATGTTGCCCA TGTCTCAAAA TTACTTGCCT CC - #AATTTTAG14880- GGCATAAAGT GTGAGATTCT GTAGCATGAG ATCATATGCT CTTAAAATAC TA - #AGTATATA14940- TAAATTATCC CTTAGCATCT TTAACATGCA TTTTTTTTTT GTAGAGACAG TA - #TCTCTACA15000- AAAAAATCTC TCTGTATTGC TCAGGCTGGT CTTGAAATCC TGGGCTCAAG AG - #ATCTTCCC15060- ATCTCGGCTT CCCAAAATGC TAGAATTACA GGCATGAGTC TCCACACCTG GC - #CTAACATG15120- AAATATTCTT TAACAGTATT CTTTAGGATA ATATATTATT CTATAGATTT GA - #AATAATTT15180- ATCAGTTCTA TACTTAATTA TAAATACTCT TGGGAATAAA ACATACTTAT CT - #AATAAGCA15240- AACAGTCGTG CTATTCCAAA CAATTTGGGA TTGCCTTTCC AAGCATTTTT TG - #GGGGTTTC15300- TTCAACTGAT TGAGAGACCC CCGGCCGGGG AAGAGAAAGA GAATTTGATT TG - #TGACACTG15360- ATGGAATGGA CTACAACCTT TTGGTGGTGA CTCTACTGGG GACTTGTCAC AG - #AGCTTATT15420- TTCTAAACAG ATGTGAAAAA TGAAAGTCAG GCTGCTGTCT GGTTGGTAAG AT - #AAAGCTTT15480- CATTAATACT TGGCAGCATT ATTTTAGCTA AAGTGTCAGA TCAAACGCCC AC - #ATTATCAC15540- CTCCCCTTCC TGATTCCAAC CGCCCATGAT AGAAAAGAAA TAAAAGACTA GG - #AATAGGTC15600- CATCAACTGG TGAATGGCTA AACAAAATGA GGTATATACA TACAATAGAT GG - #TTATTGAA15660- TCACAGTAGG GAATGAAGTA CTGATACATG CTACAATATA GATGATCGTC AT - #AAACATCA15720- TGCTACGTGA AAGAGGCCAG ATGCAAAAAT GTCACATATT ATATGATTCT AC - #TTATTTGA15780- AAAACTCAAA GTAGGCAAAT CCATAGAGAC AGAAAGCAGA CTGGTAGTTT CC - #CAGTGCTG15840- GGGAGAAGGC AGACAGGGAA GTGACTGCTT AATGAGTATG AAGTTTCCTT TT - #GGGATGAT15900- GAAAATGTCT TGGGACTTAG ATAGAAGTGA TGGTTGCACA ACACTGTGAA TG - #TAGTAATT15960- GCCATGGAGA TGTACACCTC AAAATGGCTA AAATGAATTC TATGTTATGT GA - #ATTTTACC16020- TGAATTTAAA GAAGAGTAGA AACAAACACC AAGAAAAAGG GAGGAAAGGA GG - #CATTATTG16080- AACAAGACAT TTCAACAAGT TTTGGAATAT GGAAAATATA CGGAGAAGTG GC - #AACTGACT16140- TACCAGAGTG GCAGAAGAAA TAGTCTATGT GAGTGTGGGG AATGGGGTGG AT - #GTGGAACC16200- AGTGAGAAAT AAGCCGCTTT ACTGGGAAGA ACTACAGAAA GACTGAGGCT TG - #GACGCAGC16260- TTGTGCTACT ACAGGTAGCA GTAAACAGGG GGATTTGTTG AACTTCAGAA TA - #TAGAGAAT16320- TTTGATGTAA GAGGTTTTTT TTTTCTCGTC TCAAACCAGG AGACTTTTTT TG - #TTCTCTAG16380- GTGAGGGAGA TCTAGAGACA GCCAAGTACA GGGTGCAGTA TCATCTAGAA AA - #TAAAGAAG16440- AGGTTTGAGT CTGCAGGTGA GACTCCTGCT CTCTTCCTGG AATGCTGGCA GC - #CAGGCTTA16500- GATCAGCCTC TCTGCCCTGC TCCAGGCAGA AGATGGAAAG ATCCCTTTCT GG - #AGAAACTG16560- ACTCATCCAA GAGATAACAG CTCATATTCT TACTTTTTAG AGCTCTCCAG TA - #AAATGCAG16620- CTCAACACTT GATCAGTTTC CAGCGATGAC CCCTGATCAG GCCCTCACTA CG - #AACCTCTG16680- GGTTTTAATT GGTTATTTAG TATCTCAATT TTAAAGATCA AAGACAGGAT CG - #CTTTTGAG16740- GAAACTTCCA ACTTTAATGA AAGAATTTAA AAAAAAAAAG GAAAAAAAAC CT - #GATAGTGT16800- AAAGAGCAGA GAAATGGCAG GGAAATGAAA ATTAAGTTAA AAAACAGAAA CT - #TTTATATA16860- ATTCTAATCC TTTGCAGAGA TAAAAAAATA CATTGCATAC CTAAAACAAG TA - #CAAGTTGC16920- CATGGAAACA GATTCATTAG TGAAGAGGAA AGAGATCTTG GAAATTAAAG AC - #ATAAAAGA16980- CAAAATAAAA ATTAAAAAAA TTAAACAGAA TTTAGAACAT AATGTTGAAA TG - #AGAGAACT17040- TTAGATCTCA AAAACAACAG AGAATCAACC CAGGAGATTG TGTGTGACTA AA - #GAAGTCTC17100- AGAAAGAGAA TAGAGGAAAG GAAGGAATAT TATAAGAAAA GTTTCAAGAA TA - #AAAGGTCA17160- TGGGCCTCCA GACTGATAAA AATCCATCTT GTACCCAGAA AAAATTGACT TT - #TCAAGAAC17220- TGAATCAGAA CCTATCCTGT GAAATGTTAG GACAAGTAGA TCCTAAAATC TT - #CCAGAGGG17280- AATCCATTCA AAGGCCTTGA ATGGCATTAG ACTTCTCCAT ATCAATACTG GA - #TGGTGAAA17340- GAAAAAGAGC AATACCTTAA ACTTGCTAAA AGAAAATGAT TTTTAACTAG AA - #TTCAATTT17400- CCATCTCAAT TAAAAAACCC ACTGTAAAGA AAAAATTCAA ATCTTCTCAG GC - #ATATAATA17460- ACTCTAAAAT TCTACCTCCT GTGCACCTAA TTTTGGCAAG TATCTCAGGA AG - #ATACACTT17520- TGCTAGAACA AGGACATAGT TTAAGAAAGT GGAAGAAATC AGATCTGGGA AT - #CAGGGGAT17580- CACATGATAC AGAGGCACAG CCAGAGGGAT CCCAGGGAGA GCATGTCCAG TG - #TGACAAGG17640- AGTGGACAGC TTCAGAAGGG ACAGCACCAG GGGAAAAAAC AAAATGAATA TC - #TGATTGGC17700- ATAAACATTT GGAAAGTAGT ATTAAAAATG TGTGTAACAG GTGTGTTGTT AC - #ATTTGCCA17760- AAAAAGAGCA AAAGGGAAAA AAAACCCCAA GCAGATGAAA AGTAAAGAAG GC - #AATGGTTA17820- ACTACTGGAA AAACAAAAAA CAATATTCAA GAAAGGAAAC GAAATCATGG TA - #TACTTCTT17880- GACTAATGGG TGAAAAATGA AGATGTACAT AGTTATTAAA ATGCAAACAT TG - #ATTATTGA17940- GTTAACCCAA AGTTGTGACA TTTGGAAGCA CGGGTAGGCA CAGTGGGGTG TA - #AGAGACCT18000- AAATCCTCAC TTACCGTAAT GTTTAAAAAA TTGCCATGTC AAAGAATAGC AG - #CATATCAT18060- ATTATTTAGA AATATGGATG CAAATGCCAG AAGAAAAATT AAAGGAAGTG AA - #AAATGTTT18120- TCCTCTAGGA ATAGGACAGG GGACGTAATA GGGAACAGAT ATTCTGCATT AT - #CTCAATTA18180- ATTCTCACAA CTGTGACTGA AGCTCTTTTG CTCTCCTTGT TTTGCAGATG AG - #CAAACTCA18240- CAGAGGGATG CAACTTGCCT AGGATCGTAT AGCCAGCAGC TCATGAGTGT GG - #AATGGGGA18300- TTCAAATAAG GTCTAGGAGA CTCCAAAATC CATGTGCTTA ACCATGAAGT TT - #TACTACCC18360- CTTCTCTGCT TCTTCATTAA GTATTTTTAG TGCCTAATTG CCCATGCTCT CT - #GCCAGGTG18420- CAGTAAAGGA GGATTACACA GGTGCAATAT GAGCCATGAC TCTTGTTGAA AT - #CAGCACGT18480- CAAAAATAAG GCTAATGAGC ACGTGAAAAG ATGCTCAACA TCACTAATCA TT - #AGGGAAAT18540- GCAAAACTGC ATTAAAATAT CACCTCATAT ACATTAGGAT GGCTACTATG AA - #AAAAACCA18600- GAAAATAACA AATATTGGCA AGGATGTGGA ATAACTGGAA CACTCATGCA CT - #GTTGGTGG18660- GAATGTAAAA TGGTGCAGCT GCTGTGGAAA ACAGTATGAT GGCTCTTAAA AA - #AATTTTAA18720- AAAAATAGAT TTCTCATATA ATTCTGCAAT TCCATTCCTG GATATATACC CC - #AAAGAATG18780- GAGAAAACAG GATCCTGGAG AGATGTTTGT ATACCCATGT TCATAGCAGC AT - #TATTCACA18840- ATAGCTAACA TCTGGCAGAA CCCAATGAAT GAGTGGATAA ACAAAATGTA GT - #ATATACAC18900- ACAATGGGAT ATTAGTCTTA AAAAGGAAGG AAATTCTGAC ACATGCCACA AC - #ATGGAGGT18960- GCCTTGAGGA CATTATGCTA AGTGAAATAA AGCCAGTCAC AAAAGGACAA AT - #ATTATATG19020- ATTCCATTTA TATAAGCTAC TTAGAGTGGT CAAATTCATA GAGACAGAAA GT - #AGAATGGT19080- GGTTGCCGGG GATGTAAAGG TGGGCATTTC TCAAAAAACT GAGAAATACA GA - #AAAATAAA19140- AATCACTCAC TGTTTGCCAC ACTTCTACCC TGGTTCTTTT TAAATCTATT TT - #TCTTACTC19200- AAAGAAATAC ATGTTTATAG TTTAAACATT CAAATAGTAC TACAGGTTCG TA - #ATAAACAA19260- GAGCGGTCCA ACTCCCCTCC TCCTAGCCCT GTGCTCCAGT CCTTTCAGAT GT - #TGTTTCTG19320- GTCTTTGTAT TTCTCAATAA CATGCCTAAA TGTATTTTCT GGCTCCTTGT AT - #TGTTTATT19380- TATTATTTGT TGAGTTTATT GCTATGAAAA ATAGAGATTA GATCACTTAC AG - #GGTCTTCC19440- TGACACCGTG CTCACCTTCC CCACCTATAT GTACAATTCA CCTTCCCTGT CC - #TCATGGAA19500- ATAATATTAC TCTTTTAGTT AAGTCACAGG TCAGTATTTA TGTTATGATT AT - #GTAAATAT19560- TGTTTATGTA ATGTGCTAGG GCTACTTTTT TTTTCTTTAA TTCCTTATCC TC - #CTTCACCC19620- TCACCACCCA ACCCCAATCT CATCCTGGAG TTCACAGTTA TCTCATTTTT CC - #TTTGCTTG19680- GTTTTCTAAA ATCTATCTCC TGGCTCTTTC TCCAACTCTT CTCTCAGTAA GA - #TAGTTTCT19740- CAGCTCTACC TTTTCCCCTT GTTGACATTG CTCCAGAGCC CTTCAACCTG CT - #CAGGTGGC19800- TATTCTGCTT GGTCACTCAC TTGTCCTCCT AGGTTTTCTT ATCTCCATCA TC - #TTGGGGAT19860- TCTGGTCTCC AATTTCCTGT GTTAGACCAA CTGTGTCCTG GATCCCATAT CT - #TTCTGTCT19920- CTTAGTTTAT TTCTTTGCTT TGATTGAACA TACTACCTAT GACATTTCTG AG - #AAACAATG19980- AAAGAGAAAT GATTTTTTGA GTTGTGGGAT GAATATTAAA GTCACTACCC GG - #GAAGGATC20040- ATTGTGCCTC TATCTGTATG AGGGATTCCC CTTGCACTTC TCAACCATAG AC - #AGCTCTGT20100- TCTGTCTCTT GAGCTCTTGG TGAACCCATC CCCCAGGACA ACATTTCTAT GT - #GTCTTGGT20160- CTGGCACAAG GTGACTACCT ATTCCCAGCA AATGCCAATC AACACCTGTC TT - #AATAATAC20220- CTTAGCTTCA ACACCCAAGG TTTAAGTTGC ATTAATCACT TAATAAAGAA AC - #CTTCACAA20280- ATGCTAATTA CTAACCTAGT CCTTAAACCA TACTCATTTA AAGAGGTGGC AT - #CTTAGAAG20340- TTACAGTGTT TATAGTCATT CAACAAACAT TTATTGTCAG CCATATAGAA GA - #CACCATGC20400- AAGGGCTTTA CATGGGTTAT CCAATGTAGT CCTCATGAAG GTCCTGTGAA GT - #GGGAATTA20460- TTGCCATTTG TGAATGAGTT TCAGAGAGAT AAAACTTCTC CAGCCATTCA TT - #CAACACAT20520- TTACTGAGTA TCTACTATGT GCTAGAAAAT GAGGATACCG CAGGGGGCAG AG - #GCACATGT20580- CCCTGACCTC TTGGAGTTTC TAGTCTAGCC TAGTCTGTTT CCAAGGGTAA CA - #GATATTAA20640- ATAAATAATT TCACAAATAG TCTATTAAAT ACATTTGAGA CAAGTGTCAT GA - #AAAAGAAG20700- TACAAGATGC TATGGGAATG TATAAAGGCC ATAAGCTGTC CTAGTCTGGG GC - #TCAGAGGT20760- GGTTTTTCTG AAGCAGTGCA TTAAGTCTGC AGGATAAGGA AGAGTCAGCC AG - #ATGAAATG20820- AAGTCTAAGG TTGGAGAGAG GGAGGGAACA GCATGAGCAA AGGCTCAGGG GC - #AGGAAGGG20880- GCTTTGCATA TACGAAGAAC TGAAAGGCCA ATGCGGCTGG AACAAAGAAT GG - #AATGGTGT20940- GGCATAAAGT GCAGCAGGGA CCGGGTCAGG GAGAAGACCA TAAAGCATTT GT - #GCACGCTG21000- TTAAAGAATC TGTATGCAAC CTTGGTGGAC GTGGGAGACA TGACTGCTGA AC - #TTGAAGCG21060- CATCCCTGGA GATGGGGATA AATGGAGGGA TGCGGGATGT GTGAAGCAAG AG - #GCTTGTTC21120- ATGGTCAGAA CCGGCATCTG AACCCAGCTC TCATGACAAG TCTGCTGCTC TT - #TTTGGTAC21180- ACAAAACCCG TTTCTTTCTC TGTGTGAGAA TGAACAAGGT GCCTGCACAT TT - #TTCTGTCC21240- CAGTGCAGTG TTTGAGGATG CTAAGTTACA CCCCAACAGC TGTGCAAAAT CT - #GTTTCTCT21300- CTTGTGTAGT GATGGAGGCT ATACATTGTG TTGTGAAAGG TGTCACTCAT TT - #GGGAAATT21360- AGAACAAAAC ATAGTCATTG CCTTTAACAG CACACAGCCT AATAGAGGCA AT - #AGGAATGT21420- AAACAGGGTC CCAAGCCAAA ACTTAACATG AGCAAGTTAT AGAATCATAT AC - #AATTCTTA21480- GGGTCATAAT TCTAGGGCTA CATGTTTTGA CTGTTTGACC ACACTATATG CA - #GCAGTATC21540- GTTAATGGTC CTGGATCTAG GCAGCATTTT CCGAAGTAGA CTTAAAATAA CA - #TCACTCTT21600- AGACTGGTCT GATTCTCTGT TTTGGCTAGA AATTGTGTTC CTCAAGAATA AT - #AACACATT21660- TAAAATCATC CTTATTTTTT AAGTTCAGAT ATTCTGCTAA ATCATTGATC TC - #CATGAATT21720- CATTGGTCAA TGTTTTAAAA CTTTCTCACA AACGGGCTTA TTGGAAATGG AG - #GCAGAAAA21780- TAAGGTGTTC AATAATATGA CCACATGGTC TAAATTTCCT ACAATACGCT TA - #GTTTACAT21840- GTGCAACACC TTTGTCAGAC ATATACCCAA TTTTGGTTTG AAAATAGCAT TT - #ACTTCCCA21900- GGAGTGGTGT GTAGGAACTT AAGGGTCCTA GTATGTATGT CTCTAGTGGA AA - #CTTTGGGG21960- TTCAGTTTGA AAAGGCAGTG TATCTCATGT GGATCCCTGT GATTCTCAGG GA - #TTCTATAC22020- TAGGCAGTCC CTTGTGGATG CCTGGGGAAG TCGGGCTGTG ATCCTTACAG AC - #CTTCTCTG22080- AGCTGCCATA CAGATGGGGC AGAGGGTGAA TGATGGAAAA AGAACAAATG TT - #GCTGATGG22140- TCCATGATTC GTCCGCAAAT ATTGTAAAAC CCTGTACTAC CTGGCTGATG CT - #TTAACAAA22200- ATAGCTTCAG GGACATTAAA AAAGTAGTGT TTCCTGGTGT GCTGGTAAAT AT - #TTATTGAT22260- ACAAAGATTG TGTAATCACA ATTTAAAATA TACAGTACTC TTGATTGTAA AT - #TCCTTATA22320- ACCAATTGAT CCCCACAGAA TGCTCTTGTT GACTTTTGTT TGAGGCTCTT GT - #ATCTATAG22380- TGTATCCAAT CTATTATTGC AATTGATGGA CAAGTGCCAT TCTGATAAGA AT - #GTGGGCTG22440- AGATTTCCCT TTATGTTAAT GAGTAAGAAG AAAGGGAAAC AGCAGAGCTA GA - #CACTGGGC22500- CTTCAATCGT TTGTTAACAA CACGAGCAAC CTTTTTGTTG AACTGGATAA TA - #GTTTTTGA22560- ATACTGGAAG AATATTTCCT CAGTCTTTTT CTGTTATTCA CCATGCATTG GC - #TACAGTCA22620- CATTTTAGAA TTTAACCTGC ATTATTAGCA TTTCTCCATC ACTTTTTATA AG - #TCTAGACT22680- GGGGATTATT AAACTGTGGT CTAGGGGCCA TATCTGGTCC CCTGACCTGT TT - #TCGTACAT22740- AAAGTTTTCT GGAACACAAC CATGTCCACT AGTTTTATAT ATTGTATATG GC - #TGCTTTTG22800- TATTACAATA GCAGAAGCAG AGTCGAGTAG GTTGGACAGA GATTTAATGG AC - #GCAAAGTC22860- AAAATTATTT AATATCTGGC CTTTTGCAAA ATAAGATTTA CCAAGCCTTG GT - #CTGGGTGG22920- TCAACAAAAC AATAAATCAA GCCTTGATCT GTAGTGTCTG CCAATTTCCA TG - #GTGTAAAT22980- ACTCCCATCA TGGCCAATTT CTATCTACCA ACATGACACA GCAAAACATA GA - #GTTGGGAA23040- GAGATGTGTA AAGTACACCG TTATAGAGTA TTCTCACTCT ATAGCTACAG TG - #GCTATAAA23100- TAACTTCCAG AGCATAGACA ATAGTAAAAT GTAGTCATAA TTAAGAACTG GT - #AAGTTTTG23160- AGTGTTTATT ACCTTTGTTT CTAAATACAA TTTATTTAAT TTTAAGTTTA TA - #TTTTAATT23220- TCGAATAATG GCTGGGTTTA ACAAGTGGTT TGCAAAATCT CTGAGAACTT AA - #CAATCAGT23280- TATCATGAGT TGGCACTATT GCTTTCCTTT GGTGCCCAGC TGTCTTCTTT TT - #TCAGCCAT23340- TTCCCTGTCT CCAGGAGATA ATCCTTTTTT TTCTTCTCAG CCTGTCTGCT TC - #CCAAAGTA23400- TCCTTTGTTC TTTTCATGGC CCTCTGGCTA CGCAGGGACC CCACTTTTTG CC - #AAACTAAT23460- CTTTTAAAAC ATATGTCCCA CAGAGTACCA TTCCCTTTCA TCTGCTTCCC AT - #CAATACTC23520- TTATTTCTAC AATAGGGTTG ATACCAAATG GCCAGCAACA ATTTGTAATA AG - #CTGTAAAT23580- GATTAATGGC CTGGAAACAC TTGCATTTTA AAAAAAGGAG TCTTGTTGAC CC - #AAAGGTTA23640- TAGGGTTTGA ATGTCTGGCA ACATTGCAGG TGTGAGGAAC GTCTTTGGAA TT - #CCTAGTTC23700- CCCCCAAAAG GTTACTGTCT TCTTCAGTGA CAAACAACCA ACCCAAGCGT GT - #ACCCTGAT23760- GCTCCTCATT ACCCCTCAAA ACTTTTTCCT TTTCAATCTT TTTAGTTTTA GC - #TCTTTATT23820- TCCCCTCCAC TTTCATTCCT TATTTAAACC TCTCAATTGT AACTGAAGCA GA - #TGTTATAT23880- GGACTTGGGG AAAGGGATCA AGAAATCATT CAGTTGTTTG TGCTTATCTA GA - #ACTGTCAG23940- CCCCTGAATT GTGTGGTCTT GGCTGGCATC TGAGCACACC TGGTGCATCA GC - #AGAATCAG24000- TGTTCTCTCA GTTCCTGGTT GGCTCTACTG TCTGGCACCA TTCGGCTGTT TG - #TACTTATC24060- TGGAACTGCC AATGGGAAGA TCACATGGTC ATTGAGAAAC CGCACCCTGA AG - #AGATGGCT24120- AAAAGCCTGG AGGGCATGCC CATCACAGCC TTGCCGGGAG TGTGAAAGGT GG - #TGTGAAGA24180- CCCTGGGGCT CACAGGACTC CCTCACCATG GGGCACAGTG TAAGAAGGTC CA - #CGGTGAAA24240- ATGCAGTAGG AGGCAGTTAC ATCAGGCTCT GGATCGATGA TATCAAGGAA CA - #ACCCAGGC24300- TGAAGGAAAA GGCGTTTGTG TTTCAGGAAA GATGTATTGA GCCTCATCCA TG - #CTCCAGAC24360- TTTGTTTAGG CCCTGGGTTA CAGCATGGAA TGGAATGAAA CCCCTGTTCT TT - #AGTTTCTT24420- ACATGTTGAG TGGGTGAGAC AGAAAGCAGC AATATGGTAA AGAGGGGGGA AC - #AGGGGAAG24480- AATGGTAGGA GATCAAGTTA GAGAGGGGAA TGGGCTAGAT CATGGAGCAA CC - #GGGGCAAG24540- ATGTCAAGCC CTTGGAAGGT TTTGAGCAAG AGAGTGTTAT GTTCTGACTT AC - #GTCTTGAA24600- ACACTCTAGT TGCTGTACAA GGAGACCAGG TCAGAGGCTA TTGCAGTTGT CC - #AGGTGAAG24660- GTGGCCAGGT AGCGATGGAG GATGAGAAGT AGAAAATTCT GTGAAGGCAG AG - #CTGACAGG24720- ATTTACAGAT GGATTGGCTC ATGAGAGGAA AAGAGGGACT CACGGATGAT GC - #CAAAGTTT24780- TTGACCTGAG AAACTGGAAG AATGGAATTT CCACTTACTA TGATGGGAGA GG - #TTGTGAAA24840- GGATGACTTA GGGGTTGGAG AAAACCAGGA GTTTGGATAT GGGCCTTAGA TA - #TTGCCATG24900- CAGATGTTGA GTAGACAGCT GCACATATGA GTTGGGAGTG CAGAGGGAGA GG - #CTGGGGTT24960- CTGGGTATCA GTATATGAAT CATCTGTGTC CACATGGCAT TTAAAGGCAT GA - #GACCAGGT25020- GACCCCCCTT ATAGAAAGAT TAGATCCAAA AGAGTAGTGG TCTGAGGACT GG - #GCTTTAGG25080- CCCTGATGCT CAGAGGTGAG GACCCAGGAA AGGAGACACA GAGAATCCTC TT - #TGTCAGAG25140- CATTACAAAA GGGCTATTTG GAAATAGTTC AGGTGGTGAC TGGGTGAAAA GC - #CCTTCGAA25200- CAGCCTCAAG GACCCAGGCT GGTGGACTGC TGGCTGAGTC CTGTTGTGCC TC - #AGAGGATA25260- TTGTAATATT TGGAAAAATT TCTCCAAGTC AAATTTAAAT TAACATGAAT GT - #CATATGGC25320- TTTTTGGTAC GTCCTACAGT CAAGCAAATA ACAATTGGAT AGGGTAGCTG CA - #GGAAGACT25380- GGGTGTCTCT ACAGTGGTCA AGTTGGAAGA ACAAAGAATG AGTGATTGAT CT - #TTTGCTAC25440- TCCCCAAGGG GAGAAGCCAC TGATAGCTTC CTTGGAAGCA CTTTGTACCT CA - #CCTGCCCC25500- AGAGTAGATT AAATATTAAG TTTCCTCCCT TCTTTCAAGT CCTAGTGCTG CC - #ATTGATAG25560- TGCTGTGACT TCAGGAAAGT TGCTTAACTT TTCCAAACCT CTATTTCCTC AT - #TACTAATG25620- AGTAATAATT CCCACCATAG GGTGTTTATA AAGATTAAAT AATTTTAAAT AT - #GTTGAAGC25680- ATGTAGTGAA CTGCAAAGCA ATATGCAAAT ATAAGAGGTG GAAATGACTA TG - #CCTATAAT25740- TACGTGGCTC AATTTACACA ATAATAGATT TTCACACTTT GCATAAATAA TG - #AGGGTTTT25800- TATACTCAAG TCACTGAACT TACTATCTTC AGGATCCAAA ATCCCCAAAC AG - #AAGGCATC25860- CCCTACTGTT AGCTCAAATA GCTCTTGCTG GTTTAGAGAG TTAATGCAAG CC - #CCACTGCC25920- TCCTGAGCTG GAAACATGAA ACAGAAGTTT CAGTTCCCTA ATCAATCCAT TC - #TTTCTTCC25980- TCTGGCTTCT GATAGGCCTC CTCCTTATCT TTGTAAACCC TGTAGCTGGT TG - #CTAGTTGA26040- AAGTGCCTCT GATCTCCCTC TTCTGCCTCC CATGATGTTG ATAAAAAGCA CG - #AGGGCACA26100- TGCAGGATGA AAACGATCGT GGTCCTGCCA GCCTGAATTA TTAAAGCATT TC - #AGTCCTAA26160- GTATGAGGTG TGTATATGTT GGGGTGTGGA GTGAGTTGTG GAGATGAGAG AC - #AGCTGAAT26220- TACATAAAGT TGAGAAGATC TGAGTTCTAG TCTTGAAATT CACAAGCCAT CT - #CTATACAA26280- TAGTTCCGTT ACTCAGTAAA GTAAAAGCAT TGGATCTAAG CTTTAAGGAC CC - #TTCTAGTT26340- CTTTCTGATT GGAATTCTGT GACTTCATCT TTTGTGGGTT AGAAACTCAT CA - #CTCTGTCC26400- AGTTATTTCT ATATTATGCC ACCAGATGGC AATGTTTCCT TAACCCCAAA GA - #AAGTTTTC26460- ATTCTGGTAA AAAGTCAAGT TTTGTTGCCA ACTTTTCCCC CTCTGAACGT GC - #AAAAGAAT26520- GATTTTCCGA AGCTGTGGAG GAAAGAAAGA ACTCTCCTTC TGAACATCTC AG - #GTGGTTTA26580- TGCTGGAAAC AGACAGGACC CTGTTTAGAG AAGATCTCTC TTTTCTTCGT GG - #ACTGGGAA26640- CTCCAGTTGG AATGATGTCT CCTGTGATTG CGTATGGTGG GAGGTGGGAG AT - #GTTGGAAT26700- TGGCGTGTCC TCAGGAGGCT TGGGGGTGGG GGAGATGTGC CCTAGCTGGT GG - #GCCTGCAT26760- GAGCCCTGCA AAACTCTGAC TTATAGAGGG GCATCAGATG CCAAGTTTTA CC - #AGACCATG26820- CAGAACTAGG AATTGCCAGA TGCACTCATA GGGCAGCTAA AATGGTCCTG GC - #AGAATCAG26880- ACTCTTTCGC TCATAAAGGT CAGAGACGCA AGAAAGTGAC ATAAAGTCCA GC - #CCTTTTCT26940- TGTGCAGATG GGGAAATTGA GGCCTAGAGC AGGTCAGCTG TCCTGATTCT AT - #CTCCTTGC27000- CAAGTTACTT TGTATTTAAA CATTTCAAGT AGACTTTTCA ATCATCTCAT CT - #TGCTGTGT27060- TCAGCTAGCG CACCTTGTTA AGCCTGTTGG CCTCCGGGCC TGCCAAGCCC CT - #GCATCTAT27120- ACACACCAGG GCATGCTGCA TGCGCTCAGT GAGACTTCAA CAGCTGACTG AT - #TCGTTCAA27180- ACCTATCAAA CAGCAGACTT AGCTAGTTGG GGAGAAAAGT CATTTAAAGT AA - #TTGCTTAT27240- TAATCTGCAA AACAAGTCTC ATAGCAGGTT TTTATTTTAT TTTATTTTAT TT - #TTTTGCTT27300- TTAACAACGA TATAATAACA ACAAACATTT GTTTAGTGTT TCCTGTGGAC CA - #GGCTCTGT27360- GTTAAGCACT TAACATCACT ATATCATGCA CTTTTGCTAA TAAAGCTGTG AA - #ATAGTTAT27420- TACTATTTCT GCTTTACAGC TGCAACAGAG ACTCAGAGAG GTTAGGTAAC TT - #GCCCCAGG27480- TCACAGAGCT GGAAGGAGCA GAGCCAATAT TCACACCCTG ATTTGCGTAA TT - #CCAGATTT27540- GATCTTCTAG CTTCTATGCT GTGCTGCCTC TTCATGACAG TTTTTCTCAT GT - #ACAGGATC27600- TGATGCAGAA ACTTATCGGA GTTTCTTACC GGAGCACCAG TCACCTCTCA TC - #ATTTTCCT27660- GTTTTGACGT GAAGGCTCAG TGATAGTGAG CAGGCTCAGG GTCTACAGAG TT - #GGTGATAT27720- CAGCATCACA CAGGACATTC AGAATGTTGA CTCCAGGGAT GTTGAGAGAT AC - #TCCTGCAC27780- AAAGCTGCCA GCACCCGTGT CCAAGAAACA CTCAGAATCT AGGTCTCCTT GT - #ATATTTTC27840- CCCACTACCT GCAAAGGTAA AGAGGAACAG GCAGTGCTGG GACCGAGGGA GC - #GACAGTCC27900- TAATGGAAGC TAGTGTGTTG AGAGTCTCCT CTGTGTCATG CTCTGAGCGA CA - #TGTTTTAT27960- ATGCACGATC TCATTTAGAC CTTGTGACAG CATGTTGTAG CAAGGACCCC AT - #CATCACAG28020- GGGGCAAATG TCTGCAGTGC AGAAAGTCGT CCTGAAGAAA TGGATGTCAG AT - #AAAAACAG28080- TCTTCATAAA TCAATGATCC TGTTTTACCT CAAAAGTGCA TGAAATGGAA AT - #GGAAATAT28140- CTTGTGAAGA TGTAGACAAA TGACGGTCAT TGCCCAGAGC AGTAGTTACT GT - #CAGAAAAA28200- GAGATAAGGA TTTCCAGTCT GACAGACTGG ATTCCTGGCT CAACACCACC CC - #CTTCTAAC28260- CATGTGACCT TGGGCAAATT ACCTAACCTT TTCTGAGTCT CAATTTCCTC AT - #CTTCCAAA28320- AGGGGATAAT ATCATATATG TTCCAAGATT GCTGTGAGTA TTAAATGAGA TG - #ATGTATGT28380- AAAGTACCTG GCCAGCAGTT TCTGGCACAT AGTAAGTATT CAATAAAGAC TA - #ATGGTGGA28440- GATGAGTATA GGGGCTACTA ATGCCCATCC TTACTCCAGA GACTTCTTTC TG - #ACCATCAT28500- GAGGCACTTT TGAATATCTA AACCCATTTA AAGCCCACTT TTCTCTATGG CT - #GGCCATTT28560- CTGCCTATTG ACAGCTAATT TGCCTCATCC TACAGGACAC CTTCCATGTT TC - #CCCAGACT28620- CCAGAAATCA GGTATTAAAT TATCAGGGCT TCAGGAGCCA TGGTCTATGA TG - #AGTTTACT28680- ACCTGTGCCC AATAAATGTT TAAGAAATAA ATAAGAGCCA ATATAACTAT AA - #AGACCAAG28740- AGCCAAAATA AGTCTCTTTG CTTGCGCTTT AGATCTTAAG AGTCCTTTAT AT - #TCAAGCTG28800- CTCAGAGTCA AACGTGTGCC TAATAAACAT TCTACAAAGG TCCTGGCGTG GT - #GTGACCAA28860- AGGAAGAGAG AGGGCTCCAG TGTCTGTCAC TGGGAGACCA GATGGACAGC CA - #CGTGGGGC28920- AGGGCCACTG GTGCCACATG TCCAGGTCTG TTAAGCCCTA TGAAAGACAC TT - #GAGTCAAA28980- ATGTATTTCT ATCTAAGAAA GAAGACTATA AATGGAAAAG GGAGAGGGGA GA - #AGACCTCT29040- CAAGGGCATC TCCCTCTAGA AGTAGAGATT GTGAATCTGC AGCAGAAAGG TT - #TTAAACAA29100- GGGATAGCAG AATGCCTGGA TGGTGTTCTA GTGCCTGAAT GGAAAAAGGC CA - #CAATGACC29160- AACAAATCCC ACCTACATCC GCCTTCCTCG CTGCCTGAAA TCCCACCATT AG - #GATTTTTT29220- TCCTTTTGGG TTAGCAACCA AGAAAGAGTA AAGTCTGGAA GACTCTTATT CC - #ACATCTTC29280- ACTTTGCAGC GCCTCTTTTT TTTTTTTTTT TTGAGATAGA GTCTTGCTCT GT - #CACCCAGG29340- CTGGAGTGCA GTGATGCGAT CTCAGCTCAC TGCAAGCTCT GCTTCCTGGG TT - #CACATCAT29400- TCTCGTGCTT CAGCCTCCCG AGTAGCTGGG ACTACAGGCA CCTGCCACCA CT - #CCCAGCTA29460- TTTTTTTTTG TATTTTTAGT GGAGACAGGG TTTCACCGTG TTAGCCAGGA TG - #GTCTTGAC29520- CTCATGATCC GTCCGCCTTG GCCTCCCAAA GTGCTGGGAT TACCACCTCT TC - #TTAATTAC29580- AAACATAAAC AAAAACTAAC AACTTTCTAG TTTTTTCTTT TTCTTTTTTT TT - #AAATTACA29640- AAAGAGATCC ATATTCGTCA GAGAATAATT GGAAAAAAGA GATAAGCAAA AT - #CAGAAAAA29700- TAAATTCAGC CTGTAATCAC CCAGAGATAA CAATTATTAA AATTTAGGTA TT - #CACTTTGT29760- TATTTCCTTT TATAACAAAA CTTTTTTTTC TTGTGAAATT TAATAGAATA CA - #ATTGAACT29820- ATTTTTTCCT TTATGGTTAA TGATTCTTGT TTCTTATTTA GGAAATCATT TC - #CTGAGTCA29880- TAAAGAATTC TCTCATATTT TCTTCTAAAG CTTTATACAG TTTTGCCCTT CA - #AATAAGGT29940- TAATAACCCA CCTAGAATTG ATTTCTGTGT ATGGCATGCA GTAGAGACAA GT - #TCTACTTT30000- TTTCTCTCAA ATGAATATTC AGTTGGACCA AGGCTGTCCT TTCTCCACTA CT - #TTGCAGTT30060- TCACTTTTTG TTGAAAAATC AATTGTTCAT ACATGGGTAG ATCTCTTTCT GG - #GCACTCTT30120- GGAGTCTATT GGTCTGTCTA TAAGTTGAAC AGGATCAGAC AGGCTGTGCT TT - #GTTTCAGG30180- TAACAAAGAA CCCCAACATC TCACTGATGA ATACACTAAA GTCATTTTTG TT - #TTCCATTG30240- GCAGTTCACT TCTGATGCAG GAGATGCATC AGGGCAATCG CCCTTTGCAA GG - #TGAAGTGT30300- CTGCACCATT GGAAGTACTC TCCATCCAGG GGAGAGAGAC TGGAAATGGT CC - #ATGAGGTT30360- TTCATCGACC CAGAATGAAA GCATCACCCA TCATTCCCTT CTTGTTACAG CC - #TATTTGTC30420- AGAACCAGTC AGAGTTCCAC CCACCTGCAA AAGGTTGTGA CGTGCTGTTT GC - #GATTTGCC30480- TGGAAGGAGG GAATACCCAG ATACAGGAAA ATGCTAGTGA CGTGCACTTC CA - #TCTAACTA30540- TCTTTGAATG AAAATGACAG TCTTAATTAC TGCAGTAAGA TAAGCAGACT CT - #ATACCTGG30600- TAGAGCAAGT CCTCTTACCC CATTTCTTCT TCAAGAAGGT CTTGGCTAGT TT - #GGAACCTT30660- GGCAATCCCA TATAAACTTT AGAAAATGCT AGTTAAGTTC TTTAAAAATC CT - #GCTGAGAC30720- TTTTATTGAA TCCATAGCTT CATTTAGAGA GAGCTGACAT TTAAATTAGG GA - #GTGCTCCA30780- AGCCACTAAC ATAGAATTTC TCTCTTTTAC TCCAGGTCTT CTTTAATTTC TC - #TCGAGTGT30840- TTTGTAATGT TTTGCGCAAA GTTCTTGCAC ATCTTTTGAT AGATTTCCCC CT - #AGGTTTTG30900- GATATTTTTA AGATGCTAGT GTAAATGTTA TTGCTATATA TTTTTCATTT TA - #CAAATATA30960- TGTGTTTAGT ATATAGAAAT TTAATTCATG TTTCTGTATT GACTTTATTG AG - #TAACCTTA31020- TGAAACTTTC TTAAATTCTA AAAATTATCC ACAGCTTCCC ATAGATTTTC TA - #TGTAGGTA31080- ATAACATAAT CCACAAAAAT GACACTTCAA TTTTTTCCTT TCTGTTTCTT AT - #GTCTTTAT31140- TTCTCTTTCT TGCATTTCCC ATGTGGGGTC CCTAGACACT GTTGAATAGA TG - #TCGTGATA31200- GTGAGCATCC CTGTTCTGTA CACAGCCTCG AAAGGAAAAT TTTCAGAGTT TT - #GTTTTAAA31260- CAATCTGGTT GTTATAGGTT TTATTGTAGC AGCTCTTCAC CAGATTACCT GC - #ATGTTTTC31320- TTTTTTCTAG TTTCTAAGAC TTTTAATCCA TTAATGAGTG GATGTTGAAT TT - #TAACAAAT31380- GCTTGTCTCT GCATGTATTG AAATGACTAT ATGACTTTTC CCCAATTGAT CT - #GTTAAGTT31440- GGTAAATTAC ACTGATATTC CAAAGTTAAA GCAATTTTTA CACTGGCACC CT - #CAAGTAAG31500- CCAAATTTGG ACATGATGTA TTTTTAAATA TATATTGCTG GTGTTGGCCT GT - #TAATATTT31560- TATTTAGAAT TGTTGAGCCT ATGTTCAAGA ATAAAATTGG CTTGTGATTT TC - #CTTCACAT31620- ACTGTTCATA TTGGGTTTTG GTATCAAGAT TACTCAAGCC TCACAAAATA AC - #ATAGGGAG31680- TCTCATTTTT TCTATTTTCT GGAAGAGTTT GCATAAGTGT GGCATTATAT CT - #TCTTTATC31740- TCATAAAATT TGCTTGAGCC ATCAAATCTT AACATTTTAT GACAGGTTGA TT - #TTTTATTA31800- AATCAATGAT TTTAATAGTT ATAGGATTAT TAGGATTTTT TATTTCTTCT TT - #TGTTAATT31860- TTAGTAAGTA GTGTTTTCCT AGGAATTTGT CTATTTTATC AAAATTTATA AA - #TTAATTCA31920- CAGAGTTGTT TATAATATCT TCTAATTATC TTTCTAATGT CTGCAACACA TG - #TAATAATG31980- TTATTTTTGC TTATAAATTG ACAATTTATA ATTGCGTATA CTTATGGGGC AC - #AAAACAAT32040- GTTATGATTT ATGAAAGCAA TGTGGAATAA TTAAATCTAG CAAATTAATA TA - #TCCATCAC32100- CTTAAATACT CATCATTTTT TGTGGTGAAA ACATTTGAAA TTCACTTTTT TT - #CACAATTT32160- AAAAATGCAC AGTACACTAT TATTATCTAC AGGTGGTTCC TGACTTCTTA TG - #ATGATTTG32220- AATTATCACT TTTCAACTTT ACAATAATGT GAAAGGAATA TGCATTCAGT AT - #GCTCTATG32280- ACTTATGTTG GGATTATGTC TGGATAAACC CATAGTAAGT TGAAAATATC AA - #TGGGCTCA32340- TCCAGATATA ACTCCATCAT AATTTGAGAA GCAGCTGTAT ATTTATCATG GT - #GTGCAATA32400- AATCTCAAAA AAAGACTTAT TCCTCCCGTC TGAGATTTTG TACCCTTTGG CC - #ATCACTCC32460- TTCATTCCCC TCACCCACAG CCCCTGTAAC TACCATTCTA CTCTCTGCTT CT - #ATGGATTT32520- GATTGCTTGA GATTCCACAT GTAAGTGAGA ACATGTGGTG TTTGTCTTTC TG - #TGTCTGGC32580- TTATTTTACT TAGCATGATG TTCTCCAGTT TCAGTGATGT TGTTGCAAAT GA - #TAGAATTT32640- CCTTCTGTTT AAAGGCTGAA TTATCCCATT GCATGTATAT ACTACATTTT AT - #TTATCCAT32700- TCATCCATTG ATAGACACTT AGGTTGATTC CATAACTTGG CTAGTGTAAA TA - #GTGCTGCA32760- GTGAACATGG GAGTAAGGAC ATGTCTTAGA CAATCTGATT TCAATATTTG GA - #TAAACACC32820- CAGAAGTGGA GTTACTTGGT CATATGATAA TCTAGTTTTA GTTTTTAAAG TA - #ACTTTCAA32880- ATAGTTTTTC ATGATGGCAG TACTAACATA CACTCCCAAC AGTGTACAAG GG - #TTCTCCTT32940- TCTCCACAGA TGTTCTCTTT TTCATTACTG ACATGAGTTA TCTGTGCCTT TC - #CCATTTTT33000- TGTCTTCATC TGTCTCAGCA GAGGTTTATC AATTTTATCA TTTAAAAGGT AA - #AAATTGTT33060- ACCTTTTAAA TCTTGTCTAT TGTATTTTTT TGTTTCATTA ATTTTTGCTC TG - #ATTTTTGT33120- ACTTCCTTTT TTCCATATTT TTAGGAGATG ACTTTGCTGT TCTTCTAACT TC - #TCTTTCTA33180- GGACTCCTAG AAATATGTTA AGTCTGCTCA TTGTATTTTT CTCACCTTTA TA - #TTTTCCAT33240- TGTTTTATCT CTTTCTTATT CATTCTGGGT AGTTTCTTCT AATCTACCTT CC - #AGTTCATT33300- AATTATCTCT TTACCTGTGT TGAATTTGCT ATTAAACCTA TCTGAATGAC TT - #TTTCATTT33360- TTTATTGGGT TTTTAAATGT TAAAATTCTC ATTCCTATTT GGTTCTTCCT CA - #AATTTGCA33420- ATGATTTTGT TTCAGCTGAT TGCCAAAACG TTTTTAGTTC AAGTTCATCT CT - #TTGAGCAT33480- AGTGAGCACT GTTGTTTTAC AGTCTTTATG TAAATACCTT CTCTTTTATT AA - #TCTTTCCA33540- CGTTTCTGGT GGAGGGACTG GCTATGAGAG ACAAAAACTT TCTTTCAGGT GC - #TTTTAGGA33600- CTTACCCATA TTTCTTTCAT GGTGTCTATT ATTTTATTAT CTCATTATTT AG - #ATACTTTT33660- CTCCTCTACT AAACTAATGG TTCAAGGCTT ATCAAAGATA AATCCTCTGT CT - #TGTTCATC33720- TCTGTGTCTC TCATGGTATC TAGCAGACTT CCACCCAAGA TATAAAGACA CT - #ATGACTAA33780- GTGAATGATT TTAGTCTTAC CTACCTGCCT GTTAACTTAC CTACTTGCAT CT - #CACTTATA33840- CTTCAACTTT TGGCTTCTTC CTCAACCTCA ACTACCCCAT TCTTCCCATG GC - #TCACTGTG33900- CTCACTGGCC TCCATACTGT CCCTTAAATA AGGAAAGCTG CCCTAGCCTC AG - #GGCCTTTG33960- CACCTGCTCT GCCTGCTGTT TGGAATGCTC TTCTTCCCAT ATACCCATCT GT - #TTTAATCC34020- CTCATCTTTT ATTCCCTCAT CCCATCTCTT CAAATGTGAT TTCTACAGAG GG - #TTCTCTGA34080- CCACCTTATC CAATAACCAG CATTCCGTCT CCCCTCTGCC ATTCTCCATC AT - #CTCACCAT34140- GCTTTATATC ACATATCACT AAGTGACAGT ATACTATAAA CGTACCCATT TG - #TTTACTGT34200- CTGCCTCCCT AACTAATGTA TAAGCTCTCT GAGGGCAGGG ACTCTGTTTT AT - #TTGTACAC34260- CACAATTATC TCCAGTGCCT TGAATAGTGT CTGGCATGTA GAAGGAATTC AA - #GAAATACT34320- TGTCAAGCTA GGTGCTGTGA TAACTACTTT ATATGAAATT AAGTATTTCT CC - #TCCAGCAG34380- CTCTAAAAGT TTAGTATGTT ATTATTGTCT CTGTTTTACT GATGAGTGAA CT - #GAGGTTCA34440- GAGAGGTTAT TTAGCATACG TATGAAGACA GAATTAGTGA GTGATTGACC TG - #AGATTTGA34500- ACTCAACCTG TGCTGTCTAA AGCTAGCCAG GCAGCCTCAC ATACATGGCA AA - #TGCCTACT34560- GAGACATGAA CATGCAGGTT GGGATCCCAA ACTGTTGGGA AGCATAAAAG AA - #AAACACTA34620- AAGATGTGGG GAGTGTAGGA CTTTTTTTTT TAATAGGCCA GTGGCCCTCT CT - #GCAACCCT34680- TTGAATGATC AGCTTGATCA GAGAATCCCC TACCCCTACC CCTGCCTCAG CC - #AGTTTCTA34740- TCTGGCTGTG TCATCAGCTG GCTGATCCAA ACAGCAATGT CAACAAAAGA AT - #GGTGATCA34800- GGCACGTAAA GCAATGTGTC AGAAAGAAAG AAAAGGCAGC TCAGATGATG CA - #AGATCATC34860- CAGATGTCAA GCACTGTGTG GTGGCACACT TGCCCGTTCA TGTTGTTGAT TT - #TTTAAACA34920- TTTGTGATAA GAACAAAAAC TTAGTTGCTT CCCTCAGGTC CTCCCTGTAT GG - #ATTAGTGC34980- AGACATCTGC CGCTTCAGGC TTTCTGATTG GTTCCCACTG GTTTGGGGCA AA - #ACCGGAAA35040- CTTCTGAGCC AAGTGCAGGG GCAGAAGAGC TCCCAAGAGC TCCTGGGAAA AC - #TAGGAAGG35100- ACAATCAAGA AACCACCGGC AGCTCCATTT GCAGGATCTC ATCCCATCAG GG - #GCTGTCTC35160- AGGAGGGGGA ATTGGAATAC CATTCACCTG TCCCCTTTGC AGATACACCA AT - #GTCTCGTT35220- CAAGAACAAG CAGAAAGGAA ACACCAGATT GCCCAGAGCA CAGGATTAGG AC - #ACACCACA35280- CAGAGCCAAC TCAGCGTATC ATTGTTTGCA TTGATCATCT GGGGATGAAG CA - #GGCTCCGT35340- TCTGGAAGGG GCAACCTGAA TAGAGAAGAG TCTGACATTG GAGTCAAGCA GA - #ACTTGGTT35400- GGAATTTGGC TCATTGCTGG GTGATCCAGA GACAGTTATT TAATCTGAGA AT - #CAGATATC35460- TTGTCTGTTA AATGGAAATT ATAGTAGCCA CTTCACAGGA TTGCTGTAAA GA - #GTACATAA35520- AACCAGGTAC CTGCAATGTA TAGTGCTAAG CCTGACACGT AGCAGGGTGT TA - #GTAAGTGG35580- TACCTCTGAC TGGGGATGGA AGCCAGAGGA GCTGGACCTT TATTTGACTG GC - #CAGAAGCC35640- AGCTCTCTAG TCACCTTCCT GATCCTTCCT TCTTCTGTGT GTACACGGAC AA - #TGTTTTTC35700- TACATAATGG AACAGTGGCC CTCAAAACTT GTTTTCATAA GAATTATCCA GG - #TTGCTAGT35760- TATTAATACT AGTTATCCAG GTTGCTAGTT ATTAATACTA GTTATCTGTG TT - #GCTAGCTA35820- AAAATACACT CAGTTCCCAT CCCCAGATTT TTCTATTTCA GTAGGTGGTA GT - #GGGTTCAG35880- GAAATCTGTG TTTTTACCAA AGTATCCCCT ACTATAGAAT TAATTTTTGT GT - #TCCCCCCT35940- CATTCATATG TTGACATTTA AACCTCCACT GTGATGATAC CAGGTGGCTT TG - #GGAGGTGA36000- TTAGGTGATA ACGATGAAGC CCTCATAAAT GTGATTACTG ACCTAATAAA AG - #AGACCCCA36060- GAATGCCCCC TTGTCCCTTC TGCCATGTGA GGTCACGGTG AGAAGATGGC AT - #CTATGAAC36120- TAGGAAGTGG GCCCTCACCA GACGCTGAAT CTGCTGGTGC CTTGCTCTTG GA - #CTTCCCAG36180- CCTCTAGAAT TCTGAATAAT AAATTTCCGT TGCTTGTAGC CTAGTCTATG AC - #ATTCTTTT36240- GTGGCAGCGT AAATGGACTA AGATGTGCAC CCTCATGCCC TTTAGGGAAT TG - #TGACTTTG36300- AGAAATGCTG CCCTAGGATT TACAGAATGC TGACAAAGCT TTGTTGACTC AA - #ATGCAAAA36360- TATTCTTATA AAGACCAAAA TAGAAATGAA TACTCCCTTG AACTCCTTTG GA - #TGTGCACT36420- TTGCGTAGTT ATAGCACCTT TTCATCATGT GCAAATGAGA CGCAAATGAA TC - #CTTAGTTT36480- GACCCAGAAA GAATGTCTTT GCTGGTAGGG ACTACGGGAG AGAGAGAAGA GC - #CAGAATAC36540- TGTAGGAAAA TTAACACCGG CCACGAGACA ACTGGTTGCT AGCTCGGTAG CT - #GTGCAACA36600- TTGGCATGTT ACTTGAACTT CTAGAAATCT GTTCTTTCTT CTGTAAAATG AA - #TATGGTCT36660- GGAAAGTAAA GACCAGTCAC CTCCTCTATC AGTTGGAGTC TAATCAGGAA GA - #AACCTAAG36720- TGTCTTCAAC AGAGGGAATT TAATGCAGGG AATGGGTCAC ACCAGTGTTA GA - #AAAGCTGC36780- AATGCCAAAG AGGGGATAAA GAGATAGCTC AAAGGTTAAT AAGAGCAGAA AG - #TCACTAGT36840- ATTCATAGGC TGAAAAGAGA AAGGGAGGAG ATAGTGTTCC CGGAATCCCT GA - #TGGGCTTG36900- TCTGGAGGGC GCTGGGGCCA TGGAGGAAAT GTAGTAGCTG CTGGAGGCAT GC - #TCAGGGCA36960- GAGAGGGAGC AGAGAAATAC CCTGGCTTCT CATTTTCTTT CTCCAGTCCT TG - #CAGGCACC37020- TCACTGGCTG AACTCAGGGG AGCATTTCTC CTCTACAGAA CAGAGTCTCC TT - #GCATACAA37080- CAAGAGGGTC AAACAGAGGA TGGCTTAATT TTTCCTTCCA TTTCTCACTT CT - #ATGATTCT37140- CTCCCTTCAG GTTAAGTAAG TGAGGGTAAG TAAGCTGCCC AGTAAGTGAA CA - #GTTTTCCA37200- AACAAGCCCA CAGCACCACC TCTATATACA GCAACTCTCT GTTTATCAGC AC - #TGCATTAA37260- CCAGGACTCT CTATTAACTG GGACTTCCAG TTCCTTAAAT TTCTTCATGG TT - #CCTGTGTA37320- CTCCCAAAGC ATCTTCATCA AACAAACATT AAGTTACGCT TAGAGACCAT TT - #CTCAATTG37380- AATATAGATA AAAGATTCTA AGGCCTTGAA AAAAATTAAT ACATGCATAT TA - #GATATAGC37440- TATAAAAGCC AGACTATCTG ATTAATTATG TGACTGGTGT TAAACTGTTT GG - #ACAAAGGT37500- TGGCTAAATT CCCTATGAAT ACTTACTTCC CTACTTCTGT GGACAAGGAA AA - #ATAGACCA37560- AAGGTTCAGA TAAAAGCTTG ATTCAATGTC ATCTCTTTTC TCACGAATCT TG - #GTCATGTG37620- TGGGAAGTGA CCCAGATCTA GAACCTTAGC CTTTGGGACT TAAAAAAAAA AC - #AAAAAACT37680- GTTGAGTTGA ATCATTAAGT GTTACTGAGG GACAGGAGAG AGGAGGGTAG CT - #TTCTTAGT37740- TCCAAGACAA ATTTTGTTAA CAAAGATCTG TGGGTAGACT TGTGTCTGGG CA - #AAAGATCA37800- GAAGATGTGC TGTTCTAGGC CTCTTTGCCC TCAGACCCAT TCCCTATCCT TT - #CCCCTTCA37860- CTGTACCCCC TTATCTCCTC TTCTGCTGTC TTCCTCTGGG CCTGATGCTT GA - #GGATCCAG37920- AAGTTTCTCA GGCTCCCATG TTCCAGCAAT CCAGGCCTCC TTCCCAGTAA GG - #GATGAGTA37980- CAGGGGCCAC ACATAGCCCT GCAAGTTTTG TAATCCAACT TGAAATCCAA TG - #GCAGAATG38040- AATGGTTATA TATGGTGTGA CCCAGGACCA CATGCAGTTG TATCACATGC AC - #TTACAAAA38100- GAGCCCCATT TCTTGGACTC ATTCCCAGAC TCAATCTCTC TGAGGGTAGG AC - #CAGGAATT38160- CGGCCCTTTT CACAATCTTC CCAGGTGATT CTCTACATAG TATAATAACA CA - #AACTCATG38220- GAAATATATT TAATGAAAAA TGAATAAAAG AATAAATGAA ATAACAAATG GT - #GATGGCTG38280- GCACAATGTG TGTATCCATT CTCCTACTGA GGTGCACTTA CTTTGCTTCC AA - #ATGTTCAT38340- TTGACAAGTA GTGATGCATT GAATATCCTT GTACATGTGA GCATGCAGTA AA - #GTTTCCAT38400- GGGCTTATAT TTGCTGGATT ATGGGCACGT GCATCTTCCT CTTTTCTAGA TA - #TTAACAAA38460- TCACTCTCCA AAGTATTTAT AACAATCAAC ACTCCTGAAC AAGCAGTGGG TT - #GGAATTCC38520- TTCCTCATCA CATCCTGGCC AACAATTATT ATCATCAGAT TTTTTAATTT TG - #CCAATTTG38580- AAGGAAATGC AGTGGCTTCT CATGTGTTAG TGTTTCTGAT GATCAGTGAG GT - #TGAGTGTC38640- ATTTTTTTTT TTTTTTTTTT TTTTTTTTGA GATGGAGTTT TGCTCTTGTT GC - #CCAGGCTG38700- GAGTGCAATG GTGCTATCTT GGCTCACTGC AACCTCCGCC TCCCGGGTTC AA - #GTGATTCT38760- CCTGCTTCAG CCTCCCAAGT AGATGGGATT ACAGGCATGC ACCACCATGC CT - #GGCTAAGT38820- TTTATATTTT TAGTAGAGAC AGGGTTTCAC CATGTTGGTC AGGCTGGTCT CA - #AACTCCTG38880- ACCTCAAGTG ATCTGCCTGC CTCGGCCTCC CAAAGTGCTG GGATTACAGG CA - #CGAGCCAC38940- TGCACCTGGC CGATTGAGCA TCTTTTTATG TGTTTAATGA TGCTCATTTT TT - #ATTGACTT39000- CCTTCTGTGC TTTCTTTTTT TTAGCAGTGA ATTTGAGTTG TAAGAATATG TA - #TTTCTTTC39060- ACTCTGGGAT TCACCTACAT AAAGTAATTT TCACTTGAAT GAAAAAGAAA TC - #AGTTGTAT39120- AAACATCTGT TTTTTCTGAA TTTTACTGGT GTAAAAATGG CCACTCAGCC CT - #GGAAGAAA39180- CAAAGGCACT TTGCCAACTG AAGTTGCAGA TGGGAAATTT TTAGAAAGGT CC - #TGTTCAAC39240- CTCTGGAAGG GGAAGATCAT ATCTGAAAGT CAGGGTAATC CACCCAACCC AA - #ATGTTTCT39300- TCTACTATGG GTTCTGAGGA TTCGTCCATG TGCTTCTTCT GCATTGCTGC CA - #TCTGATTT39360- CCTTTGCTAG GCTCCTCTTG CAACTTGGGC TACAAAGAGG TGCTTCATAG TC - #CACAGTCT39420- TTGCCTCACC TTCAGTCTTG AGGTGGTCCC CTAGGAGTTA TTGGTAGTTG CC - #GCTGGAAG39480- CCATTCTAAC AAACCTGGCG AAGGCACAAA AGGATAGAAA GCCTTTAGCC AA - #TATGGTGC39540- CATCAAAAAC AAACAGAGCA CGCTGCCCAG TCCTCTTCTG GTTGCCTTTA CT - #AATGCATC39600- AGTCATACTT CTTCTGCACT CGATCTTAGC CAAGAGGTCG AGAAGCCATA GT - #CATAATTC39660- TTCTGAAATT AATCTCTTCC TGCCCCACCT CCCCATCATC TGTCTTTGAA TT - #CCCAGGGC39720- TAGTACTCAT AAGATTATCT CTTTCTTCTC CTTTATGAGG AGACCCATTC TT - #TTTCACAA39780- ACCAGCCACA AAAGCAAGTG TCATTACCCC CTACCGGAAA TACCAGACAG AG - #AGTTCATC39840- TGGGGTTAGT TTCTAATCAA GCCTCCTGCC CGGGTTTTTC CTGCTCCTGT CT - #TGAAGCGA39900- CCACAGGGGG AGAGCAGTTT CCAAATATGA TCCCTCCTTT CCACTGTCAC TT - #GTCCAACC39960- CCGACCACTA TCATTCTTTT ATTTGCTTCT CCCCTGAGCC AGCCAAGAGC CT - #AGGTCAGT40020- GACAGGGCAG GCAGAAGAGA GAGGGGCTTC CAGGAAGGAG AGGGAGCAAC CC - #ACAGAAGA40080- GGCAGCAAGA CAGGAAGGCG GGCAGGGGCT GAAAATCCAA TACATATCTA AG - #TACATTTT40140- TCTAGGATGG GCTTCTACAC TCAGCCAAAA CATATATTGC ATATTGTTTG TA - #TTTTTTAG40200- AGGTTTACAG GTCTCCCTGA AAGTCCCTCT GTGGAATTAT AAACCTCTAA TA - #AAAAATCC40260- CAGGGTTAAA GAAAGGAAAA GATGAAGGAG AGGCCCACAC TCTGAAAGGA AA - #GGGTTCAG40320- CGACTCCTGG AAGGTTCTGG ATGGTGCTTC CTTGACCAAG TCAGCTGCTT CT - #TCTACCTG40380- GTCTCCTTTG TGGTTCAGCT GGGGTGGGGC TTACTAGAAA AAGCTGTGGG AG - #GTGGTTGC40440- TCCAACGTAT GGGGGCTGTC TGTAAGTGTA GGTGTTATCT GATGAAAGCT GC - #CCCGGGTG40500- AGGGTTTGTA CAGAAAGCTC CTGGTGGTGG GGAGATAATG TCAAGCTTCT CT - #CTCTCTCC40560- CAGATCCTGG TTGTATCCTC TGTCCCTCTC CACCCCCACC CACTCACCCA CA - #GACTTCCA40620- AGGAACCGGC GCCTGCAGAC ATGCCTCTCT GATGCCCTCC CAGTAACCCC TG - #GCAGGCAG40680- CACAGCGCCA AACCTCTTGG CCTTACCCCA CTGGGCCCAT GACCCAGTGG CT - #GTGCCTCT40740- GGGTCCTCCC TGTCCTGCAA AGAGAACTGG GCCCTCAGTC AGGTTCTTCT GC - #TCCAACCC40800- AGTGGCCACC TGTGCTCTTG GGGAGCTCGG GGGAGGCTGG GAAACTTTCA AA - #GAGCAGTT40860- AATCACTAAC TAGCTGGAGA TAAGAGAGAG AGAATGAAAC AATTGAGAAA AT - #GCCCAACC40920- CAGAGGTTAG TGCTTCCCTG CCTGCACACG CCAGAACCTG GCCCGCCCAG AG - #AAACTGGC40980- GATCAAACTG AGTTTGTTCA CTGGAGAGAG CTGACATACA GTCTCTAAGG GG - #CTGCAGTA41040- TCCCAGGCTG AGGTCCAGTG GCAGCCGCTG CCCCTTTCCT CCTAGGGCCC TT - #TCCTTCAG41100- CCATGCCTCA GCCCTGAAGA CAAACAGGAG CAGTTTTCAA GGAGCCCTTC CC - #TTATCTCT41160- AAGGTCTGGG CCTGGAATTC AGCTTGGCCC ATTTACTATG CCAGCTCTGT GC - #AGGGTGCA41220- GAGATCCAAG ATAAATCAGA CAGGGTCTCT GCTGTCAGTG TGCTCAAGGA AA - #GAGGCTTT41280- TAGGGGAAAC AAATCTAAAC GACTGCCAGC TGGAACTTCA ACTCTGTAAA GC - #AGCACCCT41340- GCCACATCTG CCTGCTGGAA CATTTTCATC TGCTGGGCTC ACGTAGCTGT GC - #AACAGCTG41400- GGGCTGGGGT CACATTCTGG GCTAATCTGA TGATTATTTT GGCTAGAGTG AG - #CTCATCCT41460- TTTTGTTTTC AGGAGCTGTT CAAGGGTGGT CTGATGGTTT GGATCAAGAC TA - #GCTGTATC41520- CCGGAGAAGA ATACGTTGAC TTTTCTGGGG TGGGGTCTGG GGCAGAAAGC AA - #GAAGGCTG41580- CCTTACTTCA AGGAAGGCTC TCCTTCCACC TTCTGCCCTC TGAGTGCCTT GT - #ATGCGCAA41640- GTGACACTAG ACAAAGTGCT TAACACTTAT TACCTGACTT GAATCTCCCA AT - #GGCCCTGT41700- AAAGCAGGTA CTCCATTATC ATCACCACCC TTCTTTTTAC AGGCAAGAAA AC - #CAAGGCAC41760- AGTCAGTTTA AATAACTGGC TCAAGGCTGC ACGGCCGATA AGTAGCAAAT TT - #GGACTTCG41820- AATCTGGGCG CTCTGGCTTC AAAGTGTGCT GTCCATTGTT CAGGTTCTGG TC - #TGGTACTG41880- GCAATGTCAG CCACACCTGG AAGCTTGCTA GGACTATAGA ATCCCCAGCT GA - #CCCCAAAC41940- TCCCCAAATT AGCACCATGA TTTTAACAAG ATCTCAGGTG ATTGGTGTAC AC - #ATTACAGT42000- TAGAGAAACA CTGCCCTTTT CACATTATAT GGCTCTGTGC TCAGTACAGA TT - #TAATTTTC42060- TTTTTTTTTT TTTTATTATA CTTTGAGTTC TGGGGTACAT GCGCAGAACA TG - #CAGGTTTG42120- TTACATAGGT ATATATGTGC CATGGTGGCT TGCTGCACCC ATCAACAGGC CC - #CGGTGTGT42180- GATATTCCCC TCCCTGTGTC CATGTGTTCT CATTGTTCAA CTCCCACTTA TG - #AGTGAGAA42240- TGCGGTGTTT GGTTTTCTGT TCTTGTGTTA GTTTCACAAT CATTCTCAGA TT - #TAGCTTTC42300- AAACTATTCA TTCCACCTGC CAACAATTAG CGAGCTCCAG ACATTGTGCC AG - #GTGAATGA42360- TGGAGGTGAA GAGACAAATT TCCTTATAGA ACTTGGCCAT GCCCTTCATG CA - #GGCAGTGT42420- GTGGAGTGCA AGTCAGGACA CTTGGATCTA AATCCAGTGC TACCACCTGC CG - #GCTGCGAG42480- ACTGTGGCTG AGTCATTTCA CCTTCTTGGG TCCCAGGTTC CTAATCGGTA AA - #ACCGGGAG42540- GCAAGCCAGA GATGTCCGGC CCCAGCAGCA TATTCTATGT GAACAGGATG AG - #GTGCCCAG42600- CAGGCAATCA GTGGGGATCT GCTGAATGAG GGAACCAGTA AATGAGTGAG TG - #AACCGATC42660- ATCCACCACA AGGAAAGAGC CCTCCATTTC CAAATGAAGA AAAGAAGTAT GC - #TAGTGGAG42720- GGGAGACGGG ATTATCTGCT GTGTGTCAGG GAAGAGTAGG GCCTTCCCAA GC - #TCCCTTAA42780- TACTAACATT ACACAGGGGT CCTCGCTTGC CCTTCTCAAT GGTCCACTCA GA - #TGATTTCT42840- CTTGGCGAAT GTCTGCCCCA CATCTGTGTG TCACTCAGCA ACTTTGGCCA CC - #TATCCAGT42900- GTGAGATCTC TAGATCACAA GGTGGGGAAA GGGGTGAGGA ATGACCTAGA AT - #CCTGGCCT42960- CTGGCCTTAG AGCCTCACTT GTTAAAGGGA AAGGGGCAAA TAAGATCTGA AC - #ATCAAAAA43020- TTATTTCAGC TTGCCTTCCC TCTCACTTTT CTCTGTCCCC TTCTCCTCTT GT - #CTTCCCTG43080- CAAACCACTT TGAGTCTCCT TTGGTTACCA AGATAAAACC AATCCACATT AA - #CTATGGCT43140- GGTATTTTTT TCGCTTTTAC TCCAAGCCAG TGCATAGTGC ATTTTGCTCA CA - #TTAGATTA43200- TGGAATCCTT CAAACAACCT GATGATGAGT GGGTGCCATT GATACCCCCA TT - #TTATAGCT43260- GGGACAACTG AGGCACAGGG TTGTTAAGCA GCTAACCTGA GGCCACTCGG TC - #ACTTCCTT43320- GTGGTGGACC CAGGATTTGA ATCCAGGTTT GCTCAACTCC AAAGCCTGTG TA - #CTAAACGA43380- CACTTCCTGC CTTGATAAGA TAATTGTGGT TGTTACTTGG CCAAATAAAA AG - #CCTATGGA43440- GAAGTTGTTT CCAATGAAGC ATATCAGCTT CTAAATCTGG CTGAACATTG GA - #CTCTCCAA43500- AGGGGCACAA AATACAGCTT TCCGGGCACC ATCTTGAAAT GACTGATTCA GC - #AAATTGGT43560- CGTAGGCAGC GAGGCACCTG TAGTTTGGTA AAGCTCCCAG GTGATTCTGA TA - #ATGAGCTT43620- GTGCAGAACC CATTTACCTA AGGAGAACGC GGGTTCAAAG GGACTGGACG GC - #TCTTCCTT43680- ATTTAGAGTA GGAGGCTGTT GGCTTCTGAG AATGAGGGCT AATTAACTTT GG - #GGAGCTTC43740- CTGCAGTGAC CTTTGCCTTC GGGGAAAGTG TGGGGATTGA GATAAGAGAG AG - #AAATCCTT43800- GGCGGCTAGG AGGAAGGGTA GGGTGTTTGC TGTCAGGCTC CAGGCTTAGC CC - #TCGTGGTG43860- TCCCTCCTGG AGATGGTGTG CACTGAGTGC AGTGGCTGCT GGAGAGTGGG TG - #GAGAGATG43920- AAGGTGATAG GGGTGGGATT AATTAAAATA TCAGGCAGTG TGGCTGGGCG CA - #GTGGTTCA43980- CACCTGTAAT CCCAGCGCTT TAGGAGGCCA AGGCAGGTGG ATCACCTGAG AT - #TGGGAATT44040- CGAGTTTAGC GTGGCCAACA TGACGAAACC CTGTCTCTAC TAAAAAAATG TA - #AAAATTAG44100- CTGGGTGTGG TGGTGCACTG CAATCCCAGC TACTCGGGAG GGTGAGGTAT GA - #GAATTTCT44160- CAAACCCAGG AGGCAGAGGC TGCAAGTGAG CGGAGATCAC ACCACTGCAC TC - #CGGCTGGG44220- ACAACAGAGA GAGACTCTGT CTCAAAGAAA AGAAGCAGTG AACCTTTAGA TT - #ATCCCACT44280- CTAAAAGTGA GGCAACCTTA GTTTTTCTGG GTCTTTAGAA GCAGAAGTGC CC - #TTGGGTAT44340- TTCTAGGCTG AGGGCCCCAC CTAGTTCAAG CCTTCTAAAC ATCCAGTGTT TT - #GCTATATT44400- CATTTACCAC TTGTCCTATT AGACTCTTAG GTCTTTTTTT TTAATGACTC AC - #TTATTAAA44460- GAATGTGCAT TTATTTACAA GGCAATAATA TCACTACCTT TAATGGAAAA TT - #AGCAACCC44520- TGGCTACACC TAGAAGGTAA CTGTTAATAA ATAGGATGAA ACCCAAGGCT GG - #AATTAACT44580- TCTCATTGGA TCCTGCAGCC TATGCTCCTT TCACTGAAGG GTGATATCAG CC - #AACTGAGA44640- CCTCCTCTAA AGTCTGTGAA GGATTGAATT AAGAGAATTG GAAAGGGCAC AC - #ATTTCTCA44700- TGATGTGATT CAATATTGAT TAATTCCAGG TTCACCTATT ATCTAAAACC AT - #GTTACTGA44760- AAGTGGCTTA TAAATACCGC AGCACCAGAA TGTAAACTCC ACAAGGGCAG AG - #TTTTTGGT44820- TTTGTTTTGT CTTTTAAAAA TCTGTTCATT GCTTTATTCC TAGACTCTGG AA - #CAGTACTT44880- GGAATATAGT AGGTGTTCAC ATATTTATTG ACTACGTGGA CTCTTTTTAG AC - #TGAGAAGC44940- GGAATATAAA GTCAGAGGGT CCGACTGGTG ATCGAATGCC TTCGTTCTGT AC - #TCAAGCCC45000- ACTCACCCAC TTAGTTTTGA GAACTCTGGT GACCCAACCT ACAGCCTGTC CC - #ACCTTCAA45060- CTTATTCCCA TTCCTTGGGT GCACGTGTTG CTGTGAGGAT CAGATGAGGT CA - #TGGATGGG45120- CAGGACTCTG AACTGCGTGC CCTCTGCACA GGGAAACAGC TGGGCCGATT AT - #AAATTGCA45180- AAGGGGATGC CTGATGGTGG CCCCATGACT TTTCATATGC TTTGGGCTGT TG - #TGAGAGAG45240- AGTGCCCAAA GCCTGATTCT GGAACATTTT CTTTGCTGTC TTCTAAATGA GA - #ACCTGCTT45300- GCTTCAATTC TCCCACTGAG CAATCATGCT GACATGAGGG AGGCGGAGTC AG - #ACCTTACA45360- TTGTTGAGAC CAGATTCTGT GTTCTACGAG TATTGGGAAG GGTGATGCAG GC - #AGGCACCC45420- ACCATGTTCC CTGTGAGTGC TTATTTTTAA TAAAAACCTT GGTATACTGC TA - #TTAATGAA45480- AATAATAATA ATAATAATAA TTACTCCTGC TAATAATATA AGGAAACACC CA - #CTGGTCTG45540- TGACTGAGCC AGCCTTGCCT GAAGGCAGGG GAATGAATTC AATGACCTCT TG - #ACACTGGT45600- CTCAGCCCTT TGGTTCTATT ACCACCTTGT AAACCTGAGG TTGTTCTGTT TT - #TATCCCTA45660- GGGAGTTGTG GTTAGAACCT GCCAGAAATT TCTCACTATG AATCAATCTT CC - #ATTGGTCA45720- CTGCCCTTTT CAACATGCCT GTCATTCAAG ACTTACGATT TCCTAGGCAT TG - #ACAGAGAG45780- AAACTGGCCA TGTGGACCAA GGCAGTGGGA TTTACGTGAC ACCCGCCAAG CC - #GGTGGGGC45840- TAAGTTCCAT TGCTGAAGTC TGATACCTGT CATCTGCTGT GGGGTGACAT CC - #ACACCATG45900- TCATTCTCCA TTCGTTCAAT ACATATTTGT GGATTCCTAA AATGCCCCTG CT - #GCTGTGAT45960- AGTCCAGCTC AAGAGAGAGG AAGTACATGA GATGTTACCA CACAGTGTGG TA - #TGTGCTGG46020- AGAGGTGAAG ACTCTGGAGC AGAGAGGCAA CAACTCAGGT GGGGACTGAA TG - #GTGGCGGG46080- GTGAGCTCAT CAGGAAAGGC CCCCCCAGGG AAGCTGTGTT TGGGCTGGGG TC - #TAAGGATG46140- AGCAGCAGTT AGCCAGGGAA GACAAGGAGT AAATGTACCT AGGCATGTGG GG - #CAGTCTAT46200- GCAATAATGT GGGGAGGAAG CAAAGAGAAA GAGAATGGGA GAATGGCCTG CC - #TGTTTGGG46260- GAAATGAAAG GAGCCAGTAT GTAAAAATCA GGTGAGAGAC AGCTGGAGAT GA - #GGCTGCAG46320- AAATAGGTAG GTGCCAGGTC ACAGAGGGCC TTGTGAATAG TATCATGGAC GC - #TGGACTTT46380- ACTCCAAAGG GCATGGGAGC CATCAAAGGG TGTTGAACAA GGAGATGCAC AT - #TATAGAAA46440- GGCCAGGAAG GCCTCTGGGA TCTCCTCTTC TCCAAACTGT GGCTCTGGGG AC - #AGCTCCCT46500- ATAGTGGTCT TGGGCAGCAC CAAACTGGTG TTTAGGCTCA GCTCACATGC AG - #CTCACAGC46560- AAGATGGTGA CAAATGACTC ATCCTCAAAC AACAGAGCAG GCATAGGAAG GA - #GGCCCCAG46620- TTAGGATCTT GCTTACCTGG TTTGCTGGTG GCCTATGCAT TTAATTGTAG AA - #CAGAATGC46680- CAAGCCACTT TTTAACCTTT CTTCTACACC ATGCCCTGCA CCTCCCCTTC TC - #TCTCTGCT46740- CTTCTCCCTT CCACCCTCAA ATTTCTAAGC CATGTCCAGG TCTCGTTTTC AC - #CTGTGCCA46800- GAGAAGATCT ATCTGACTTT GGCCATGGAA GAGGTATAGC AGGTATCAGT TG - #GAGAGGGC46860- TGGAAAAGCT CCCTGGTGCT AGATATGGAC GACCTGAGCT TCCAGTCCTG GC - #TCTTGCAG46920- CCACCAGGCA TTTGACATGG GCAGAAGCAC TTTTCCTCAC TGAGCCTCTG TT - #TCCTCATC46980- TGTAAAATGG GAATCATGGT GATGGTGTGA TATTTGAACA AGTTTTTTTT TT - #TTTTTCAA47040- AATTGCTTTG TAAACTGCAA AGCTCTGAAT AAGTGTTTAT TTGGGATTAT TA - #GGAACTGC47100- TTTGCTGGAA CAGTCTACCA GAGGGATGGA AGGAGAGGAA CTGAGAAATC CA - #TTCTTTGA47160- AATATTTTTA TCATATGAGA TACAAATATG TATCTATATA AATATAGATA TA - #AATATGAA47220- CAAATATATC TGTCATAAAA TTTAAAAAAG GATGAACCTT GCCCCCAATC TC - #ACCCCTAG47280- CAGCAACTAT TAATTTTTTG TTGTATATCT GCCCAGACAC ATATAAAATA TA - #TATTCAAA47340- CAAAAAATAT AATCATATTA TAAACTTTGT TTTTTAGCTT GTTTATTCAC AT - #TACATGGA47400- AATCTTTCAG CATCATGGCA TATAGATCTG TCTTTTTAAT ATTACTTCAT GG - #TCTAGGTG47460- AACCATAGTT TATTTAGCAT TTTCCTTTTG GTAAACATTA AAGTTAGTTG CA - #ATTTTTCA47520- TCATATATTT TTTCTGGTCT TTTGTACATA TATCTATGAG AGAAATTCCT AG - #AAATAGGG47580- TTGCTGACTC AAAGGATACC AGCATTTTAA ATTTTGGTAG GTACTACCAA AT - #TGCTCTTC47640- ATAAAGAGTG TACAAATACA CCCTCCCACA AACAGAGTGC CTGCCTTCCA TG - #CCTGGACC47700- AACCACAGGC ATTACCACCT CTGCTGAAGC TTTTTCATGA GACAAGGTCT TG - #CTCTGTTG47760- CCCAGGCTGG AGTGCAGTGG CGTGATCTCT GCTCACTTCA ACCTCTGCCT CC - #CAGGTTCA47820- AGTGACTGTC ATGTCTCAGC CTCTGGAGTA GCTGGGACTA CAGGTGCGTG CC - #ACCAAACC47880- TGGCTAATTT TTGTATTTTT GGTAGAGATG GGGTTTTGCC ATGTTGGCCA GG - #CTGGTCTC47940- GAACTCCTGG CCTCAAGTGA TTTGACTGCC TTGGCCTCCC AAAGTGCTGG AA - #TTACAGGC48000- GTGAGCCACC ATGTCTGGAC TGCTGAGGTT TTTTTTTTTT TTTTGAGACC AA - #GTTTCACT48060- CTTGTAGCCC AGGCTGCAGT GCAATGGCAT GATCTTGGCT CACTGCAACC TC - #CGCCTCCC48120- AGGTTCAAGG GATTCTCCTG CCTCAGCCTT CCAAGTAGCT GGGATTATAG GC - #ATGTGCCA48180- CCATGCCCAG CTAATTTTGT ATTTTTAGTA GAGATGGGGT TTCTTCATGT TG - #GTTAGGCT48240- GGTCTCGAAC TCCCAACCTC AGGTGATCTG CCCGCCTTGG CCTCTCAAAG TG - #CTGGGATT48300- ACAGGCATGA ACCACTGCGC CCAGCCTTGC TGAGGCTTTT AAAACCATGA AA - #CGCTCCTC48360- CTCCCTCAAA TGGTCATGTG GCCACTGCCT GCTTCATCAC ACTGCTCCTC TG - #TCTGACAA48420- GCCTGTTCTT ATATAACACC AGTAGGTAGG GCCATCCGAG ACATGGTTAT CC - #AATAAAAT48480- GGTAAGAACC AGCCCTAGGG TATTTGGGAA ACTGGCTGTG AGGGTTCAAT GG - #AATATTCA48540- CATTTCCAAA CATAAAATCT AGCAGCAATG GAGAAACGTA CTTTAAGCAG AG - #AGTTTTGC48600- GCCTGACACA AGAAATTATT ATTATTGTTG TTATTGAAAG TTCTGACACA CA - #GATCTCGG48660- TTGTGTTTGG AAGGAGGATA GTCAGAGAGA GGAGGAAGGT ATGAAGAGGT CG - #AGGTGTTA48720- GTTTTAAAAA GTGTGTCTTT GTCATTGTCG AGCTGTGGCT GGTCCCACAA CC - #TGGTTCTA48780- TCAGGCCTTT GGTGTTACAA AATGCAAAAC ACCAGGCAAC CAAATAGCGT TT - #CCATGGAA48840- GTATCCCATG ACCTCTGGTG CTGTGTACAG GTGAGACAGT GAGCACTCAG AA - #AGGGATGG48900- CCTGGGTGGG GAGGGCGAAA GGGGCCTCTC CAGCCTCTGC AACATAAAAC AA - #GGGGCCAA48960- TGGAAAGTTC TGGAACTGGA TCACTAAGAA GACAGGCCCC ACTGCTGGCA TG - #AGTGGGAT49020- GACCAAAGAA TTAGGAAACT GAGATTGGAG TTGGTCACCA ATTCAACTGG CC - #CATTTAAA49080- AATTTTCATA AGCAGGGACA GAGGATCAAG CCAAGAGCAC TAGGGAGATG GT - #GATGAATG49140- GAAATTGTGT AAGGTAGATG GCTATGTGCC GGGGAAGGAG GAGAGAGGAT TC - #AGAATTAT49200- AGGAATAATA CATGAAATGA CTGACAAAAG TAGCCTTTTA TGTGTGTTAT GT - #AATTTAAT49260- CCTCTTAACC TTATAGAGTT AGCACTGTCA GGATCCACAT TAAAAAAAAA AA - #AGACGAAG49320- CAGAAGCTCG GAGAAGTCAA ATTACTTGGC CAAGGTCAAG GTCACACAGC CA - #CATGTGGC49380- AAATCTGGAA TACAAACTTA GGTCTATCTG ACTTTAAACC AAAATGCTGC AT - #ATAGCTTC49440- GATTTCAGCA CAGCAGGGTT CAACTTGGAG ATAGAGGGTG GTGTTATAGA TT - #ACCAGATA49500- CGATAGTGGT AGGTTTTCTT CTGTCTTGAT GAAAGATGAG CTATTTTTAT CC - #TGTTGCAG49560- GACAACGCGA AGGATCATGA CTTCCATTTT TGAACTGACA TTGTAGATTT GT - #GTATATTT49620- GACAGCTCTA CCACATTCCC AACCCTATGC CCTCCTATCA CTCTTTTTGA GA - #ATACTGGG49680- CTAGTTGGGG GCAGTGTTGG GGGACTTGGG CCTGGGCGTA TGCTGGGAGG AA - #AGGCAAGG49740- AGATTATGCA GTGTGGTAGT AGGGACTGGG GGAAGTTTTT TTGTTTTTTG TT - #TTTGTTTT49800- TAAAATCCTA GTTGGTCCCC AGTGGAGCCT CCAGACCTCC TCAAAGTCTT TG - #AGGTTGTG49860- ATTAATTACC ATATAAACTA GACAGTCCTT GGCCTTGGTG TTGCCATTCC AG - #CCTGTAAT49920- TATCTTCATC ACAAGTTGCT GTCTGGCTTT GTTCTGTAGG TAGAGGCTCT TT - #CGTAGGTC49980- CCTGCATGTC CCTGAGTCAC TAGCAGGCTC ACTTGTGCTT ATCCAAACTG GT - #GAATCATT50040- AGCTGTCACC CTGGAGAGCA GTGCAGTTTG GGAAGGCGTG GGTGCGCCCA TG - #GAGAGGGT50100- GATCCCCTCT CTCTTCTTTC CAGGCATGCG TAAGGAGCAG TGGCAGAGAA TT - #ACGGAACA50160- GAGGATGCTA TCATAGGTGA CCTATGAGCC AGGCACGTAC ATACGTGTCA TC - #TCAATGAA50220- AGCTTTACAG CACAGGTTAT ACAAGTAGTA CACAGGGATA AACAGCAAGG TT - #CTTAGGTG50280- GGTTTCAGAC CTGGCTCTGT CATTTATCTA GAGGTATGAC CTTGGCCCAA CC - #TTCCTAAC50340- TTGTCTATGC CTTGATTTCC TCAACTATAA AATAGAGATA AAAATGGTAA CT - #GCATCCAA50400- GAGCTTTTGA GAGGAATTGA TGCAAAGATG CAAGTACAGT GCCTAGCAAA CT - #GAAGCACT50460- CCATGAGGAG TGGTGATGCG GATGCTAATG CTGATGCTGG GACAAACTTA CA - #CCCACTTT50520- ACAGATGGGA GAACTGAGCC TCAAGTTGTT TAAAGTGGCA TAGCTAGTAA GT - #GGTAGACT50580- TGGGATGAAA ACCCCAGTCT GTTTCCAAGT CAGGAACCCT TTCCTCCATA AT - #GCCGTCTG50640- CATAAATTAG ACTGTTGGAC TGAAAAACAA TCCGTTCAAA CCACAAGGGT AC - #ATTGGCCC50700- AGGTTGCTTC TATGTTTTAT CCTCAATCTG AAGCAATATA ATGAGCAATG TA - #ATGAGATT50760- ATGTTAATAT TTACTCAGGG TTCTGGGAAA CCCAGAAGGG TTTCAGGGTA AA - #CCATCTCC50820- CAGCAAGCAA GGGCTCGCCC GCTAATTCCC CTTTCTTCCA AGACTGATCA GA - #TTGCCCAG50880- TGCCTAGTAA AATGCCAGTT TCCTTCTATG TGGAAGGGAG CAAAGCTGTC AG - #CTCCTGCT50940- GGGGCACAGG GAGAGGATGT TTCTTGTGGA TAGGTAGGTG GTGCTTAGGG GT - #AGAGGCTC51000- TGAGATCAGG CAGACATGGT TTCTATCTGT CCTCCCAGCA GTGTGTCCTT GG - #GTAAGTTA51060- CTTAATGTTT CTCAGCTTCA ATGTCCTCAT CTTAAGATGA GGGATTATCA TG - #CTACTTTG51120- TGGGGCCTTT GTGAGGATTA AATGAGATCT TAGTATCTGG CACATAGTAA GT - #GCTTAATA51180- AAAATAATAA GGCAGAGCTG GGTAGATTGA GGGTTTGGTT TACAGCACTT TG - #ACAGCAAG51240- TTGCTTGTTT CCTGCCATTC AGAGACCCTG GCCAAACTAT GTCCATTGTG GC - #CACAAGAC51300- CATTGGCATG TCAGCCTCCA AAAGAGAGAT GACTGCTCAG CAGGCATTAA CC - #AGATCAGA51360- GGTTCTTTGA TTCAGCACAG TGCTCTCTTT TTGCACTGCT CTCAGTCTAC CA - #ACAGTATC51420- AATCACAGCA ACCATTCATG GTGCAAGGTG ATCTCCCTAA ACTTACATTA TA - #TCTTTAAT51480- CCTCACAGCA GCCTTGGGGG ATGGTATTAT TTCCATCTGT AGATGAGACA AT - #AGGGGCTC51540- AGAGATGGTA GGTAATTGCC CAAGGACACA TAGCTGTTGG AGAAAGTAGT AT - #TGGAGCAA51600- AATCTATGTG TGTGCATCTA GATTGACCAA CCTTCCTGGT TTGCCTGGGA AT - #ATGGGGTT51660- TTCTAGGATG TGGGGCATTC AGTGCTAAAA TCAGGAAAGT CTAAGATGAG TT - #GGTTACTC51720- TATATGCGGC CTCTCCGTGG AGGGTTGGTT GGTGGGCCTG GAAAAGGGAT AG - #GGATAAGA51780- GAGAGAAGAG GAGGACGCAG AGAGAATGGC AGAAGCAACT CTGCACTGTT TC - #TTTCTGCA51840- AAGATGTCTT TTCAATTCAA CCTGCTTGTT CAGTTCAACA AGCAGGTTTG AA - #TGCCCTCG51900- TCCTTGGAGG GAGTCACGTC AGGACTTTCC GGGTATTTGA CCGTGATGAA GA - #GCGCTGTC51960- TGCCAGGGTT CGCCAGGCTG GGTGTGGAAA AATGGTGCCC CAAACCAGCC CC - #ACATGGCA52020- GAATAGGAAA CATGCTGTCA TCTTGCTTCA TCTGAATCTC CATTCCATGA GG - #GCAGGAAT52080- TGTTTTCTTT TTTACTTCTA TAGCTGAAGC CCCAGTGCCC AGAATATGGC AG - #AAACTCCA52140- GAAACATTGG TGGAATGTAG ACTATTGAAT AATTCCAAGT ACAAACCAAT GG - #TCCAGGGA52200- GATTTAGATT CTGATGAAGG CAATCTGGGG AAGACTGAAT GGAGAAATAG CA - #TTGGAAAC52260- GGTTTGGATA CCACGTGTTG GGATCAGGAA GCAGAGGAGC ACAGAATGCT TG - #TGCAGAAG52320- TGACATGGGC CCACTGCACC TGGGGTGGAC CCTGTGAGGT AGAGTTGGAG AC - #CAAGGGCC52380- TGAGGACTGG ACATGTCGGT GGAGACCAGG TGGTGGAGGA TGGAGAATGC CA - #TGCCCTCA52440- GGGAGTTTGG ACTGCCTGTC GTTAAGCCAT TTTTTTCTCC AAATTTCAAT CC - #CCCTCATT52500- CCATTGTCAC CATATTTGCC ATGTCTGTGT ACCTACCTAT ATTACTTATT TA - #ACACTTTT52560- CCTTCAAGTG ACTTACTTTT TAACTTTACA TTTGTTTTCA TATCAAACAC AC - #ATGGCTGT52620- TAAAATAAAA ATTACGATTT GAACTTAGAA TCATCTTGCC TACCACATGA GG - #TAGGTGTA52680- CTTCCCTCTG AGGACCACAG CTCCAGCAAC TGGGGAACCG ACAAAGATTT TT - #GAAAGAAG52740- AAATGATTCA GTTGCTTTTT GGGAAGACTA CACACGTGAG GAAGTACTGA GT - #GGAAGATA52800- TGTGCATAAA ACATTGGCGC AATTGTGACT AACATGGTAA GAAATATTAT CA - #ACGCAAGT52860- TTGGGGGGCA TTTCAAAGTC TCTCAATGGT CATCCGGATG AAATATGCAA GA - #ACTGCTCT52920- CTCTCTCTCT CTCTCTGTCT TTTCTCTTCT TGGTCTCACT TTGCCCTCTT TC - #CCAGCAGC52980- TCTGCCTTCT CCCCCATGCT TGCTGCCAAC AGCTCTGAGG AATGGGAGGG AT - #TGCAGTTC53040- AAAGAGTAAA CAGGTCTACT CTGAGTAAGG CTGTGGGCTG TGCAGTGACC CC - #CAGTGGGT53100- CTGGGTGCCT GGTAATGATG CCTGCACTGG CATGATGCTG TGGCTTTCCA GG - #CTTGTTTT53160- ACCTGGTTGT GCAAAGAATG TTACCCCCAG CCAAGGCTCA AGTTCACAGA CC - #ATTGGCCC53220- ATCCCCTAAT AAGCATATTA TTCCCAGCTG GGCATTGAAC TTCCAAGTTA AG - #GTGACCTG53280- CCAAACTGGA AAGAAAATGG ATTTGCAAAA ATCAGATGTT TGCCAACAGC AC - #CATCCCCC53340- ACCACAACCA TAGACAATTG TGAGATCTAA AGTTGGACTC CCTGAGGTTT TC - #TGCCCTGG53400- TGGTTCTGGC AACTCCTGGA GAGCCACAGA CTGATGAATT TGAGGATCAT AA - #ACCTTAAG53460- AAGACTTTAA AGTATTTTTG GCATTAATTG ACAAAGTCCA CAGCAAGCCA GG - #CATGCTCT53520- TCTCTCCCAC TCCCCTTGTC AGAGATGTCT CTTTCCCCTT GCTCTTCTTA CC - #CCATTCTT53580- TCCAGCATAA CCAAGCTTAA TAGCTTCCAT GTTTCCACTG TAAGGAAGTG AG - #CCGAGTGT53640- GGTTGGTCTG TTTCACAGCA GGGCTATCCT CACACGAAAA GTTTTCAGAT GC - #ATTGACTA53700- TGCAGATTTT TGGCTCAGTT TGCAGAAGAC TTCCTTATTT CAGTTTTACT GT - #ACACCCAC53760- CTACATAATA CTTTTTGGTT CTTAGAATTT CAGAGCTATT AACCTCTAAA CT - #TAAATCAA53820- AATTCTCATC AAACTTTCCT AGGGCCTTGT CATAAAAGAA ACTAAGTCTC AA - #AATAGGAC53880- TTTTTGGCCT AATTTCCTTG TCCAGGAAGA CAGATTGACT AATTCCAAAC CC - #TGGACTCA53940- CATGTGATTG CTAAGAATAG GGGTGGGGGA GAGAGAGGGG ACAAAAGTCA TA - #GACATGCC54000- ATGACACATA TTGGGAGATT TCATCTGAAT TTCCCCTGAG TATGAAATTA TT - #CAGAAATA54060- ATTCCAAGGG CTTCTTTTCT GACATTCCAC CAGTGTGCAG GTGCATATGT TT - #TGAATGAA54120- CTGAATGGAT AATTTATTTA TACAAATGAG TCTTTTTGAA TAGTTGCAAT GG - #ATGTGCTG54180- TCAACTCTCC AATATCACTT CCAGGGGGTT TGTAGATGCA TTCTTTCCAT GG - #GCATCAGC54240- AGGTCTGGAT CTCCTGCTTT CTATCTGAAA GGCACTGGTC TGGATCTCCT GC - #TTTCTATC54300- TGAAAGGCAT TATGGGCAGC AGTCTGGTTG ATTTTATACT ACTTTGATAC AC - #TCTCAATT54360- GCATACTAAG AATGAGGATG GAGAAACTGA TAGTGACCCT CACCCCAATT AG - #GTTTCACT54420- ACTGCCCTTG ACCTTCATAT TTAATGCCTT TGTTATCACA GCAACTCTTT GC - #TCTATTTC54480- TGGATCCAAA TGCCTAAGGA TCTCCCTGGG GTGTTAAGCT TGCTCAGTGC TA - #TTAAACCT54540- GGTGGGTGGC AGAGTGACCT TTGTATCACA AGAGCCTCAT GACTTCCCAG GC - #AAGACCAA54600- GTCACAACTT TTCCAATGGA TTTCCCCTCG ATTCTTATTC TGAGCATTTA GC - #TTTTTAAA54660- TATTTGGCTC TGAAGGGCAG GGGCTAAACA TTGTTCTGTA AGATCCAAAC CT - #GCTTGTAT54720- ATTTTATACT TTTGTTTTTT CATTTCAACT TTCCGATCTC GCTCTTCTGA GA - #AACATTCA54780- CATTTCCAAT TGCATTCCAG AACTGAGCTT GACTTTCCAT GTCCATGTAA GA - #TCTTGTAA54840- TTCAAATTTC AGCCAGCTGC TAAGCTTCTC TTTTCTGGAG GGGATTGTGG TT - #AAGAGATC54900- TTGTTTTGCA ATGACGCTGT CTGGTCTGAG CTCCAGCTAC TTGTCTTATT TA - #CTGTGCAA54960- CCTTGGCCAT GTTAACTTAT CAGGCTCATG AGGCTCGGTT TTCTCATCTA TA - #AAGTGAGA55020- AAATGAATAG TACCTATCTG ATGGAGTTTT TCTAAGGCTT AAATGAAGTA AT - #GCAAATTA55080- AATTCTTAGT CTAGTCACTG GGAAAAGATG AAAACTTAAC GAATATGAAT AG - #TCACTATT55140- CTGTTTCTTT TTTTCTATGC CATTCCGGCT TCACCTCCTT CTCTTACTTT TT - #CCCTTTCT55200- TTTTTCATTT GTTTTCTTTT TTTTTTTTTT CTTTTTTGAG ATGGAGTTTC GC - #TCTTGTTG55260- CCCAGACTGG AGTACAATGG CATGATCTTG GCTCGCTGCA ACCTCCACCT CC - #CAGGTTCA55320- AGCGATTCTC CTGCCTCAGC CTCTCGAGTA CCTGGGATTA CAGGTGCCCA CC - #ACCATGCC55380- TGGCTAATTT TTGTATTTTT AGTAGAGATG GGGTTTCACC ATGTTGGCCA GG - #CTGGTCTT55440- GAACTTCTGA CCTCAGGTGA TCCACCCACC TCAGCCTCCC AAAGTGCTGG GA - #TAACAGGA55500- TGCCGCACCA CTGTGCCTGG CCTCTTCTAC TTTTTCTTAG AAACATGGAG GG - #TTAGTTCT55560- CTGGCCACTC ATATGAAACT TCATTCCCTG CTAAGGTGGA AGTATTGGAG TT - #CAAGCTCT55620- ACACTTAGTG GAGGGAGTAA ATAAGCATTT CCAGAGAGCC CACCAAGTGC CA - #TGCAATCT55680- CCTAATGCTT TGTACTATTT CTCATTTAAC CCCCCAAACA GCTCACTGAG TA - #TGTTAATA55740- TCCCCAATAA ACAGATAGGG AAACTGAGAC CTAAAGTTTG AGCAAATATG GC - #AAAGTTTT55800- CCTAGGCTGT CTGGCTTTAA AAACAATGTC CTTTCACCGC ATCAGGCTGC TT - #CTGAGGAG55860- CAGAGCCACC TTGCTTTTGT AAGTCTGTTG GAATAGGCTC TGAGATGCCA CA - #CGTTATCC55920- CAAATAATTA GGCATCTGGA TGGAGATTTT ATACATTTTC TACTTGGACC TG - #AGTTTGCT55980- GTCTCTCATG GTTCCTGGGT GAAAGAGGCC AGGCCCTGAG ACCTTTACCC AA - #GGTTGGCT56040- CTACCAAAAT ATCTTCTTGA GTGAGTTCTC TGGTTGATCA TCTGTGGAAC AA - #TGTGGGAG56100- CCTACTAAAT ATGAATGGAA AATGAGGAAT GCAAAATGGA TGGTTTTCTC CA - #CTATCACC56160- TCACCCTTGG AGGTGTTTGC TGATTTGGTA GATGTGTGGA GGAACTCAGG AG - #TCTGAATT56220- TGTAAAGGTA ATTTGGATGC TTCATTAGCT TAGAAAGGAC ACAGCAGGGA GA - #ACTATATA56280- GCAGAGAAGG CTGGATGCCT ATGAGGGTAG GGAAGGGAAA ACAAGGGGGT GG - #GGCTGTAG56340- CTGCCCTACC TCCGGTCCAT ATATGGCTGC ATTTCTTTAA TCTCTTTTAC TT - #TTGGGATT56400- CCATGGTAGT AAACAAAGAG TTCTTATGTT AAAACAATTG CTATCTAATT GT - #ACAGCATG56460- GTGAATATAG TCAATAACAA TGTATCATGT ATTTGCAAAT TGCTAAGAGA GT - #AGATTGTG56520- TTTTCACCAC ACACAAAAAT GGCAAGTATG TGAGGTAATG CCCATGTTAA TT - #AGCTCAAT56580- TTAGCCACTC CACAATGTGT GTGTGTGTGT GTGTGTGTGT GTATATATAT AT - #ATATGTTT56640- ATGTATATAT ACACACACAC ATATATATGA CATGTCAGAA TGTCATGTTT TA - #TTCCATAA56700- ATATATACAA ATTTTATTTG TCAATATAAA AAGAATAATA CCTGGAAAAA CA - #AAAAAAAA56760- ATCCTAAGTG CTATACTTAT AAAGAAATCT TCCTCATACA AAAAAGAAGA AA - #TTCTGGCC56820- ACAGGAAGGT TGCCTGAAAA TGGCCACCTT TTTCATGATT TTCCCTCCCT TT - #CTGAGACT56880- GAGAAATGAG CCTTCTTGAA GACCCTGATG GAAATACTGT GAAGAAACTA AG - #ACAGTTGG56940- ATTCAAGAAC CAAAATGCTT ATCGTAGCAG TGAGGTTGGC TTGAAGTCAG GG - #AACAGTGT57000- AAAGCTATTT GTGGGGAAAG ATAAGGCCAG AAAGAGATTG ATAAAATACA GG - #CGAGACCA57060- AAGGAACAGG GCAGGGGCAA ATTAGTTTAG GCAAGAATAG AGGCGTCTTG AT - #ATTAATTA57120- AAATATGGAG GAGGAGTCCA GAAAATTCAT CCTTGGTGCT TGGGTAAGTT TA - #GCAACATG57180- TTCAGATGCC TGAGTTTTGT GTGTGTATGT GTGTGGGCAT GCACGTGTGT GT - #GTACACAG57240- TGGGTCATTC TTCTCAGGAA GAGTGAGCCA CTCTCCCCTC CTCCAGCACC AA - #AGTGGCCC57300- CCACCTTGGC ACGCCAGTGG CACATGCCAT TGGGCCAGGA TTTGCTCAGA AT - #GCAGGCAC57360- ACAGACATAA TGTCAGGAGG CATTGCTGGT GTGTGTCACA TCAACCTGTT AG - #AACAACTG57420- TCAACGTGTG ACCTCCCAAA CAGAACTCAG GTGCCCCCTT CAGAGACCGT AA - #AGCTTGTC57480- CTTAGAGGAT AATGAAGATC CCCAGGAACC TCATCTAATC CAAAACCAAA AG - #ATTTGGGA57540- AATGTGACCT TTAGAGGGGA GTAGCATTAA GAAGCAAAAT GATACTTATT AA - #TTCTGTTG57600- CTTATTTGAC TGTAACCAGT ATAATAAATG ATCATATTCT GCTCGATTTA AT - #TCCCCCTC57660- CCCATAAGTT TCACAAGACC AGAAGGAGTT TCTTCTTCCC ATTGGTCTTA CA - #TTAATATT57720- CTTGTACGGC TTTCACTAAA TAGATGCCGT GTTCTGCCCT GGAGGTAACA CC - #ACGTCATT57780- AGGAGGAGAT GATAGACAGA AATATATACA AACACACACT TGCTTTCAAA AA - #TAAATATA57840- GGCCCTCTAG TTAAAAGGTA TTGTGTAAAG TGTGTGAGCA TCCTCTTTCT TG - #CAAAGCAA57900- GCACACAGCT TCCATTAATC TTGTAGCCAC AGCCTGTGTT GGTGTTAAGA CT - #CAGATTCC57960- TTAACGCTTG ATACTTGGCT TAAAGAGATT CTTTGTCCTG GCCTTGATTT GG - #GAATTAAG58020- ATCCCTAGGG TTTTTGGTTT TACAGTATGG ATCTTCTAGG AGACAACCCG AC - #TGACCTCC58080- GGGTCTCCAG GCCACCACAC ACAACCTGGT TTGCTTTGCT CTGTTCCCCT TT - #TCCTCTGT58140- GGGGACCAGC ACAGGACTCA ACTCAAGGGC TCTGTGTCTG TGCACAGGTT GG - #AGAGGGTG58200- ATAGGGCCTT GACCTGTAGG GACAACCAGG AAGATTTCTA TGCAGAGTAA TT - #GGGTTTCT58260- AGAGTTTGTT TCAGTTGATT TGAGGGCAAG CTGCTTGGCC TCTCTCTCTT GA - #TTCTTCCC58320- ATCCACAGAA TAAAGACAAT CAGCTTTGTT TATCACTCTG TTCATTTTGC TA - #TGTCTTTA58380- TCAGCCCCCC AGAGAATTCA GGAGCACAGA ACAAGTGCTG GAGGTCTCTC TT - #GCCAGAGT58440- CCTCCTTGAG AACTTACAAT GTGTCCATAT TAAGGATCTG CTGTGTTTGA TG - #ATTTTGTG58500- ATTACACTTT AAACTTCTTA TCCATAAAGG ACATACTTGA TATATCTGAG AC - #TTGTAGTA58560- GAAGGCCTTG AGACATCCAT CTCATCCCAT CATTATCTAT CTATCATCTA TC - #TATCTATC58620- TATCTATCTA TCTATCTATC TATCTATCTA TCTATCATCT ATCTATCTAT CG - #CCAGTACT58680- GTCTTGTTGA AGTTGGCAGT AGGGTGAAAG ACCTCAAACT CCAAAGGACT TT - #CCGTATGG58740- ATGCAATATA CCTGCAATTC TAGCTTTTTT GTGTTTTTTT TTTTAGGTTG GG - #GGTGAGGG58800- GTATTGTTTT CATTTTTGTT TTTCTTCTGG AAGGTTCAAC TAAGACCCAA GT - #AAAAAGAA58860- GAATCAATAC TTAATAAGTA CCCAGCAAGT AGCAGGCACA CTTTTAGGTA CT - #TTATTTAC58920- AAAAAAACCT CCACAAATAA AGTGGCTTGT GAGTATGAGG TGACATCTTT CC - #CTCCCCTC58980- CCACCATCAC TACCCCAATA TGACTCGTCT CAATAGCCCT CCAATCTAAA AT - #GGACTAAA59040- TACAAGTGGA TAAAGAAATG GAGATTTAAC CAGAATTCTT CAGCTATAAA TT - #ACAGGGCC59100- TATAATTAAA GGTGATTGGG ACTGGGTCAG AGAGCCACAT CACTTTTGTG GT - #TGCATTTG59160- AAGTTCACTA TCTCTTGACC ACACAACCCT AGCCCTTCTA CTCCCACCCT GC - #TGTCTCAG59220- GTTAATCTCA GGCAATGGTG TAAAGAAGGC CAAGTTTGTT TCCCTGGAGT CC - #CACGGGCT59280- CTAGCAATAA TGCTTCCCTT TTCTCATGAG TGCCCCGCCA CCCACCCCCC TT - #CACCATCA59340- CTACACACAA ATGCCCTGCA GTGGGTGGAA TGTAGTTACT TCAGGTTGTG CC - #TGATTTGT59400- CTCTCAAGCA AAACTCCAGC AGGCCATTCC CTCAGGGCCC TGCTCTCAGA TC - #TGGAACTG59460- ATAGACTAAT TGGGGCTAAT GTGATAATGG GAAATAATGA AATTTGTTGT TT - #TTATCAGT59520- GTGTATATGG GGCGGGGTTT ACATTTGCAT TTTCACAGGG CCCTTGGCAA GT - #TCACAGGG59580- TTGAACAGTT GGGAAGGGTG GGAATGTCTG GGGCAGGTTA GGGAGGCAGA GG - #GATTTATT59640- AGAACTCCCC TAAACTGCAC TGACCAAAGC CTCAAGCCCT TCTTCAAGAC CT - #GCCCAGCT59700- TCCAAGACCT TCCCAAGTCC ACCCTTGTTT TCCCACTGAG TCTTTTACAC TT - #TCAGAAAC59760- CTCTGAATTT GTGTAGAAAC TAGAAAAAAT AAGTAAGAAA AGACTAATAC TA - #CTGCACAC59820- TCACTGTTCC CCCTTAATAT AATAACCAGT TTTTATTCTA TTCAGTCAGC CT - #TTGACCAT59880- AAGCAGACCT TTTTTTTTTC TTTTTAACAC AAGTAACTTC TTGGTTTTGA TC - #ACAAAATC59940- TTTATCTCTG CCAAATCTCA ACTTCCCTTC CCTCTCCCAC AAAAGGGAGG CC - #CGTTGAGT60000- CAAAGAAATC TGCTTAGACA CTTTGCTCAT GCCAGGCCAG TGTCCTGGAA GG - #TTCAACAG60060- AGAGAGTTAA TGGTTGGGGG ATGGTATTTT TCTTTGCTAG GAGCAGTCAT TC - #ACCCGTAT60120- GGGAGAAGGT ACATTTGTGA CCCAGTGAAG CAGGTACAGG TAACTCCCCA TA - #TGTCCCTT60180- GGCCCAAGGG AATAGAGGTT GCCTGGGTAT TTGAATCCGT AGATCCTCCC TA - #ATATTCCA60240- CCTTCTTCTT GTCCAAACTG TGCTTTTTTA TTTCCAGTTT CAGCATTTTG GT - #CTTCTCAT60300- CTCTAACTCT TATAGGGAGT GTCAATAAAC CTTTTAAAAA AGATCATGTA AG - #TGTCAAGA60360- GGAAGTGAAG AACCTAGATA ATCCACCAAC CGGATAATCA GCTCTTGCAT AT - #TTGAGAGT60420- TGACTGCTTG ACCTAAGCAT CTCCTCATAA GGTACCCTCC CTCCCAGGAC CT - #TCCCTTTC60480- AAACCTCTCA AGGCTCTTAC CTGGGGCCAG GGGAGATAGG CTTTTCAAAG TC - #CATTGAAT60540- TGCCAAGAGT CTCTGTCAAG AAGGCAGTCA TGGTGCCTGG AGAGGGAACT TG - #CTGGGAGC60600- CCCTTCAGAG CCTGGTACTT ATAGAGCTAG GGAAAAGATC TTGATGCCAA AG - #CAGGGTGG60660- ACTAAATACA GACTAATAAA TGAGACAGGT GCTCAAGAGG GCCCCTCCAT AC - #CATCATCT60720- CCTCCAGATT TGGACTTCTA CTCACTTTGC TTTTACATTC CCTCTTCCCG AT - #GGTGTCTT60780- TGGTGAGCAG GGTGCTTTTC ACCTGAAACA GCCTCTGAGC TGAAAAGAAC AG - #TCACCACC60840- AAATCAATTC CTCATCCATT AACAGGTTGT CTCTCTGTTC TTGAGACACA GG - #CATTACCT60900- GGTTAGACCT GTTTTGTTTG AACACTAACG TGTGAGTTGG CCAAATGCAA AT - #GAGCCAAT60960- GTTTGTAATC CTTTATTTTA TTTTTTTAAA GGGCTGGGTA GCCAATCAGA AG - #AGGGGGAA61020- GTGACTTAGG GAATTCCCGG TTGGTGGCTT ATTGCTTAAC ATCCTACAAA AT - #GATTTAAA61080- ATTATTGTTA TATGCATTTA TCTTCACTCT GATGAGGGCT CAGACTTGAT AA - #CGCCCGTG61140- GTGCCCCATC CCTATAGGAG CTGGTGAGAT TGCAGCCTGC TGCCTCCCCT CC - #ATCAGCCA61200- CAGCTATTGG ATTTCCCACC CAGAATCTTT AGGTAAATGA GGTAAGTCCT GA - #TTTTTAAA61260- ACTTCTTTTG AATCTGGAAT CCAAACACTT GAGTGGAAAG AGAAGCCTGC TT - #TAAACTGG61320- ACAGATGAAA CTAGAACAGA CTCTTGGAGA CGGCTGGCAG GAAGTGAAGC TC - #ACCTTACC61380- TGGGCTTACC TCACTGGGTC AAATCAGAAT TTTATTTTGG AGGGCAGGTT GG - #CTACTTTG61440- GATATTATCT GTGAATTTCC TGCATTGTCT GGACTTCTAA TCTCTGTGAA TT - #TAAAAGCC61500- CCCTCGTTTC CCTATGCCTG GGTGGCAAAA CCATTCCCCT GGGTTGAATT CT - #TCTGGAAC61560- AAATAGGCAG CTAGAGATAG GTGGCTCTGA TATAGCTCAG AGAAGAAGTG GT - #TGGCTAAG61620- TAGCTGTTAG GGCTCAGAGT ACACGGTCTC GCTTTCTAGA GATGTCTTCT GC - #TGGTAATT61680- TTTCTGACTT ATGAGCTACA TGGAAAGGCC AATTTGTTTT TAATATGTTC CA - #GGACTGGA61740- AAATGGCTAG AAATAGGCAA GAACATACAC AATCACACTG GAAAAAGTGG CC - #AGGCAGCC61800- AAGGCAGGCA GAGGTATTGG GGAGAGCTGA ATATCTACAA AAACAAAAAT TC - #AGAAAAAA61860- CAAAAATCAA TTTTGGCAAA GGGCTTCACT GTATAACAAG GGGACAAACT AA - #CCCTTTGT61920- TTACAAACTA ACCCTTTGTT TACTCCATTT TGTCCAGAAA ATACAACAAT CA - #GTTTTGGC61980- AAAGGGCTTC ACTGTGTAAC AAGGGGACAA ACTAACCCTT TGTTTACTCC AT - #TTTGGGAG62040- ACTATGATCA GACAGGCAGT TGTGACTCAG CAGCAACAAA TGCCTTCTGA GA - #CAGGGATT62100- CTTTTGATTT TGCTTGGACA TTGTGGAGAA GTGTTAGCCC CAATGTGGAC TG - #ATCTGGGA62160- ACAGTGGGAA ATTAACTTCT TGTTGGCAAA TATCAGGCTG AGGTGAGAAA GC - #GACATTTT62220- CACCGTCCAT CTTTGCTGAT TTACCGTGCT CCCAGGATGG TGGGAGTGTG TG - #TTTTTAAG62280- ATGGAGAGTG TATGCTTCTG GGTTCAAGTT CACAGGTGTC TCTGCTGGTT AT - #CTGCACTC62340- ACCTTGGTAA CAGGGAGAAA GTGAGTGAAT GGATTCCAAG AACTTACTGA TG - #GAAGTCTA62400- ATTCAGGAGT TGGTTCTGCA GCCATGGAGG TAAAGATGTG TTGATAGTCT TT - #CAATGTGT62460- AAAAGGGCAA TTAGAGATTC TGTGTGACTG TGTGTTAATT CCACTGGGGT CA - #GGGGAAAA62520- ATTTATTTCT AACAGAAAAG AAGAAGATAC GTTATTAGGA AGAATTTCAT GG - #CTAGGAGA62580- TACTATCAGA AAAGGCTCTT AAGAGATTTT AAGGATGACT TTAATAGCCG CA - #TTTGAAGT62640- TTGCAGAGGA TCCACTTTTC CTCTTTTTGT GACCTAAAAT TCTGGGATGA TG - #AAATAACT62700- CACCAATTCC ATCTTCTTAT AATATGGAGT CATGTAGACA ACACCATTTT CA - #CACAAATG62760- GCTAATGGTA TTTAAAAACC ATGATGGAAT GTGAATTGGG AGTCATTTGG AG - #GTCTGTAG62820- TTGAACTTGA AAAAATAATA AATGTAATGG AGACAATACT TCACCGTGTT TC - #CAAAATAT62880- TTTACAGAGG CATTTTAAAT GAAAGTCACT TTGAGGGAAC AGCTGTGCTG TA - #AGTTCTCT62940- TACATGACTG CGCAAGATGG TAGCCTTCAT CAAGACCTCT CAAGGTAGTG TG - #GGTAGGGT63000- GACGTGTTTG ATTCAGGCCT CGTTTGTTAT GAAAAGGCTC AAATTCAATT GT - #ATTTGTTA63060- TTTTTTTGGT TAAAAAGCAC CTATTTGTTC AATTCAAACA ATCCTTTTTG GT - #TTTTTTTT63120- GAGATGAAGT CTCCGTCGCC CAGCCTGGAG TGCAGTGGCA TGATCTTGGC TG - #ACTGCAAC63180- CTCCGCCTCC CAGGTTCAAG TGATTCTCCC AACTCAGCCC CCCGAGTAGC TG - #GGATTACA63240- TGTGCTCGCC ACTATGCCCA GTTAAGTTTT GTATTTTTAG TAGAGACGGG GT - #TTTGCCAT63300- GTCAGCCAGG CTGGTTTTGA ACTCCTGACC TCAGGTGATC CACCTGCCTC AG - #CCTCCCAA63360- AGTGCTGGGA TTATAGGCTT CAGCCACCGT GCCCAGCCAT ATTGTTTTCA TT - #TTTAATCT63420- ATTAGTCTAT CGTGATCTCC CAGTGGAAGT ATCTTTGGCC TTTGTGGACG TC - #AGGAAAGC63480- CCTACATTCC CACTCGCGAT TCCATGTTTA TGGGTACCCT AAATGCTCCC AT - #TAATTGAC63540- CAACTTTACC CTGATCTTCT TTCAATATCT TTCTGACTCC TTGAAGGTAT GA - #GACAAAAT63600- GGAAACTGAG AGGTTAAAAG GTTTACTAGG TTGCATTCAA TTAGCGAATT GG - #AAACTGGA63660- AGGAGCTCCT ATCGGGTCTC AGGTCAGAAC GTGAGTGCTT TTGGCCAAAG TT - #CACTTCTG63720- AGGAAGTAGA ATTTCGCTTT CTGGAATCTT GCGATATTTT ATTTCCTCTA TA - #TCTTTCCC63780- ATGCCCCCGA CCCACCCAAT CTCCACAAAT TTGGGGATTT GAGCACTGGG TT - #GTGATCGT63840- TAGACCATCT TGCTTTTCTG AAAGCCCAGG GCAAGACCCC TGCTTCATGT CA - #CAGTATCA63900- AACACAGACA TAGAAGCTTG TACAAATTAT TGAGAAGTTA TTGTCTTTTC TC - #CCTTCCTC63960- CATATGGAGT CATCTCTATG CCCTTTCATA CAGATGTGAT TTACGAAGAC CT - #CTGGGTTA64020- GGGGTGGGGT GGTGAGCAAG AATCCCGTGG CAGAATCTGC TAACACACTT GA - #GAAGCAAT64080- GTTGTGGTTT TAAGGAACTC AATCTAAAGC TTGAACCTGA TTTTCAGGGA TA - #CCATTTTG64140- CTGCCGTTTC AGCCCATTTC TCTTGTTAAG ATCGCTCTCT GGTAGAGTTG AC - #GTGACACT64200- CATTTCTGTT GTGGGTGGGG CCCTGGTTGG GAGGCATTGG CTCCACTGCA GC - #CTGGGTGT64260- CTAGAGACCA CATTCTCACC CTGCCTTTGT TACTGGGAAA CCGAACGCGG CG - #CTGTGGCT64320- TTCAGCTTGG GTAAGCCGGG TCTGCGGCGG GGATTGCCAT CTGAAGACAG AG - #GCAGGAGG64380- GCAGCCACAC CTTGCCCAGG TTCTCTTAAA TCTCTTGCTC TATAACTGAA AG - #GAGGGCAT64440- AGATAATTAA CTTTATTTGA CATTTTTCAT ATCTAATTTT TAAGAATATG AT - #TTTAAAAT64500- AATAGATTTG TTCTAAAGAG CAAACAATCT TGCTGTTATT AAAAACGTGT TT - #ACTTAAAT64560- TGAACGGGGT TTCAAAGGGC CAAGCTACTA AGCTGTGCAG GAAACAAACA GT - #GCAGTGAG64620- GAGAATGGCT CCTCACCACA GCTATTCTTA GGGTGGGACA TAGTTTCAAG CC - #AAATGACA64680- TTGATGTCCG GAAACCAGGA TGTGCTGAAG TAGAAATTTC CAGGGATCCC TC - #AGAGTTAT64740- TTGCTAAAAT GTTTATTATT CTTCAGAGGG GGGTGGAAAT ATTTCTTTAA GA - #GTCTTCCT64800- TGAAGAATTT TGAACTCCAG CTTTGGAGTG ATGGGAGCAC AGTGCAGGGA AG - #GCGGGATG64860- TGAGGTGGTG TGCTGGACGG CAGTCTAGGG ACCTGGTCTA GCACTGGCAG AG - #CTGTGTGT64920- CCCAGAGCAC ACATTCCCCT TTGCCAGGCT TTAGTTTCCT CCTCTAGGCA AA - #AGGGTTTG64980- AACCTGACCA TCTTTAAGAT CCATTTTAAC CCTCAGATTC TGTGGCTGTG GT - #GATTGGGG65040- GTGGTGGGAG TACCTGGGGG TCAGCAGGAT AAGCACGAAT CTGTGAGAGC TG - #AGAACAGG65100- TGGGAGAAGC CTTCTAAGGA TGAGGCAGGA AAGATTAGCA AGAGCCCTTA AA - #TGGATTCT65160- TTAGGGCCTT CAGAATTTTG GCTAAAGGCT ATACTAGTGG AGGTACTAAG AC - #CTGACACC65220- TGGAGCCTTT ATTAAGGATG TTAGAATCCA CTCCCATGAC AACATCCCAG CT - #TTGCCAAT65280- TTGCCTCATG TGTCTCAAGC TGGTGGGAAT GTAGAAGTGG ATGAAACAGA CT - #GTTTTGTG65340- ATGGCAGGGA ACAGCCTATG CACAGGGGCA GGTGCTCTAC TGGTGTCTTC TA - #TAAAACGC65400- CAAAGCAGCC CGCCAGAAAA TGGACATTTA GGCACTCGTG GTGTCTACTG AG - #TTTGTATG65460- GTACTGATGA GCTTGCTTGA CTGATTATCC ATGACTTACT GAGTAGATCG AA - #CGTATGTG65520- GACTCACTTC TCCTAGAGGA AGACCCTGTG GCTGCCCCAG CCACTGAGCA GC - #CTAACCTG65580- GAGACCCTGA TGTGCCCAGA AAGCGTCAAC CTTGTATCTG GAGAAACCAG AA - #CTTGCAAC65640- AGGGCCAAGC AGGGTGGCCC ATTTAAAGAG GCTCCTAGGG TTTTAATTGA CC - #TTGTTTTA65700- AAAGAGACAC CCTGTAAAAT ACTCCTATGA AAACTTATTT CACAAGCACC TA - #ACCGCATT65760- CTGTCTTTGG TTTGTTTTAC GGGGCCGGGC CCCTTGTTCT GGTCAATTGG TC - #TGCATTAT65820- CTCTCCTCCT CCAATCTCAC CACACACCCT GGCCTCTGGG AGGCTTCCTC CC - #TTCTTTTT65880- TTTTGTTTGT TTTGTTTTTT TAGCATCTTA GTTGTTACTA GGGGTACTTG CC - #TACTTATT65940- TAAAATATGG CCAGTATAGG TGCATACAAA ATGTGCTTTC TGATTAAAAC AA - #AGCCAAAA66000- ATAAAAAGAA ACCAAAATGC CTATTATAGT AGTTGGATTT TTAGACTAAC AG - #ACCACCTC66060- ATTAACCCTG TCATTTTACC ATAACAACTT ATTTTTATCT TTGTATGACC TT - #GTCTCAAT66120- GTCCTTTTTC TTTGATGTTG TTGCAATTAT GAACATCAAA TTTCATAGCT GC - #TTTTCCAC66180- CCCACTTTCT ATCACAGAAG CACAATAAAT AATCTTGGGG GCTGGGCTCT TG - #TTGGCCCA66240- ACTGTGGCTT CAAAACATTT CAGTTGCCTG TCCAGCCCTT TCTTAGCCTG AT - #ACAACATC66300- CCCCAAAAGT CTGTTGAGCT TTTCCTGGAA TAAGAAGAGG GTCTTCTACT TT - #TTGAATAG66360- AGCAATGGAG ATTGGAGAAT ATGGTCATCT TGTGGAGGTT ATTCCAGGCT TC - #TTCTTAGG66420- AACCTTAAAA AAAATCTCCT CAGTAGGGCT GATGATATAT TCTGGACAAT AA - #GGTGAGCA66480- GAGTCTGAAA GATGAGAGCA ATTTTCAATC TTGTCATGAT TTCATCTAGT CA - #GCCTCATT66540- TCATCTAGTC ATGAGGCTGA CTAATGATAA GACTTGCTTT GTCTTTGCAG TG - #TACTCTAG66600- ATTTGACTCT AAATTCAGCC TCTGTCTTGA TCATGCCCAC TTAGAAAATT AG - #AGTGCAGC66660- TAGCTCACCT TTTAGTCATC TTAATTCCAC TAGGCAGAAG GCTGTGGGTC AA - #GGAATGTT66720- GATGGAGTAA AATTTGACTG CATGTGTATC TGAAGGGGTA GGAGGCTAAG AG - #ATTTTATG66780- GCTTGGAAGC TGCTGAGATG TGGTGTAAAG AACACTGGAC TTAGAGTCCA GA - #CACCTGAG66840- TTTAAGCTGG ACTCTACCAC TGGGTAGTTG AATGACTTTG AGTGAGTTAT AT - #AAGCTCTA66900- GCATCTAAGT TTTCTCATCT GGAAAATGGA GTTAATAACA TCTACTGCAT TG - #GGCTGTTG66960- TAAAGATTAA ATTAACAAAG AATGTGAAAG CACCTGAACA AAAGCTTGTG AG - #TAAATAAT67020- TAGTAATTTG TGGAATGAAC ATCAAGGGAA GTCTTCAATT TGGGTGTTTT CA - #GTGAGTTT67080- CTGTTGGGTC AGAGTGAATG GATATTAAAT TCTGGGATTT TGGTTTGTGT GT - #GTGTGTGT67140- GTGTGTGTGT GTGTGTGTGT GGCGATCAAC ATTGGTTCTT CACTGTGACC TT - #AGGAAAGA67200- AATGCAATAG GGTTTTTATT GGGAAGGTGG GTAGCAGGGA GATGCATGAA CC - #ATATTAAG67260- GGGGGACCTC CAAATTGAAC CTTGTTTTGA GTCAACTGCA AACCACAACC AA - #GGAGGTCC67320- TGGGAGACCT GGGGTGACTT GGGGTGATTG GGTATGCAGC ACATTCCTGT TC - #TTGTGTCC67380- TGATGCCTGG CAAGTAGGGA CCTGCAGAAA ATACTGATTC TCCTCCAGGC AG - #TTCACATG67440- ACTAGCTTTT AGGAGTGAGT ATACCGTTGC CCACCCCTAA AATTCTTGAT CA - #TGTCTCCA67500- GATGTCTACT GACCACTGAT GCTGAGGTCA TGAATCTTGG GCATTCTAGA GG - #CTTTGGGA67560- AAAAAAATTC TACTTACTTC TTTTGCCCAG ACACTCTGGG GTCTACCTCT TG - #GTAAATTA67620- TTCAAATGAG GTTTCTGGTC ATGCAAATGT GGTTTCTAGA GCCTATTTGA AT - #TGAACAAG67680- TAGTTCTTAT TATTAGTAAA ACAGCAAGGA TCCCTAACTT GGGGTCCAAG GG - #TAAATTCA67740- GGGTTTCTGT GAACTTGGAT GTAAAAAAAA ATTGTGTTTA TTTTCAATAA TC - #TCTAACTA67800- GAATTTAACA TTTTCTTTCA ATATGAATGT AGGCAAAACT CCATGGTAGT AT - #TAGCTGCA67860- ATTGTGACTA TCACCAGGAT AAATCACATT TTCATGTCTT ATTACACCTA TT - #ACATATAT67920- CACAAAAAGT GGGTATTTGA TATCAAGTTA GATCTGCACT AGGTAGATAT TC - #TTATTTAA67980- TGTATTAACA AGGAAGCACA TATATTGTTA TCAGGTTGGT GCAAAAGTAA TT - #GTGGTTCT68040- TGCCATTAAA AATAATTACA AAAACAGCCA GTCTGGCCAA CATGGCGAAA CC - #CCATCTCT68100- ACTAAAAATA CAGGTGTGGT AGCACACACC TGTAATCCCA GCTACTTGGG AG - #GCTGAGGC68160- AGGAGAATCA TTTGAACCTG GGAAGCAGAG GCTGCAGTGA GCCAAGATCA CA - #CCACTGCA68220- CTCTAGCCTG AGCAACAGAG TGAGACTCTG TCTCAAAAAA ATTAAAAAAT AA - #AAAAAAAC68280- TCTGTAATTA CTTTTGCACC AACATAATAT GATATCACAC ATTTATTTTA AA - #AAGTATTT68340- TGACATTGTC TTTTAATATA AATTTTTTTA AATCTTATAA TATTTTAATT TG - #TCATGTAA68400- AAATATTATT TTGAGAAGAG GCCTGTAGGC CTCACTAGAT TACAAAACAG AT - #CCATCGTA68460- CAGATGAAAG GTTAAGAACA CCTCATTTAC AGCATTCTCT CACACACGAC TA - #ACGAAATG68520- ACTTCTGAAC AGCGCCAGTT GATAGATGTT CTCTGCCAAA AGGGGAATAT GA - #TCTTCCCA68580- TATGTTCCTG CCTATGGGTA GCCTTGGAGT TGTGAAGGGA CTTTGGCATA AT - #GAAGATGA68640- TAATAAGAAT GATAATGGTA ATTTGTTGAG TGCCTGCTGT AAGCCAGGTG GT - #TACAGTCC68700- TGTTCAATGT CATGTTTAGT TTAATCCTCC CAATGACCTC AGGAGGTAGT GC - #ATGGAACA68760- AAGACAGAAG AGATCCCCTG CCCACCCACG GTAATGAAAC ATGGGTACAG GT - #GAAGGCAA68820- AAGTGGGGAC TGACCCTTTG GAGATGGCTG ATGTCACGAG TGTGCAACCT GT - #GCAGTTCC68880- ACGGGGCCCC ATGCTTAGAA AGGTTCCATG TTTGGTTTAA GGCTCTGCTG TT - #GCCATCTT68940- AAAATTCTTC GTAAGTTTTG AACAAAGGGC CCTGCATGTT CCTTTTACAC TG - #AGCTCTGC69000- AAATGATGTA GCTGGTCCTG CCTCTGGTTA TGGTGAAATG GAATGTATGA CA - #ACTCCTGA69060- GACTGGGAGT CTGGGAAGCT GCTGCGGAGA GCCCTCTCCT CATTTTCATC AG - #GCTCAGCT69120- ACGCAACCTC TGGTGGAAAG CTATGGCCTG TTGAGGAGGG AGGATGTCGT TT - #TTGAGTTA69180- GTGAGTTTTC CAGTTTTGTT TGAGCTCCAA AGCTTTCCTC CAAACAACTG GA - #AAGATGGC69240- TGAATAATTG GCTGAAAGGG ATTTAATCCC TTGAAAAACC TTTCTGGTAG GG - #AGTTGCTG69300- GCAATACTGG TGGGTTTTTC ATGATTTTAT TTTACAGAGG GCTTGCTACG TA - #AACCAGTG69360- AGCCAGGAGA AACAGAATAA AGTCTGTTCT GGAAGGAAAA ATGAGACCTG GT - #GTGCCACG69420- AGTCTAGTGT TCTCATAGGA AGGCTCTAAA AACAAACTCA GCTTTCCTGC TA - #TTGAATGA69480- TTATCTCTAT AAAAGGAAAC TTTACTTCTT CTAAAGGAGA GGTCGTCTAA TT - #TGTGAGAA69540- AATTCAGATG TTATTTGCTT CTTAAGCTGC AAGGATGCTA ATGAAATAAT TC - #TCATGAAG69600- TTCTGTTGGT GTTTTAGGGC TAAGTTTTTA TAGACTGTTC CAAAATTCAA AA - #CAGGGATG69660- TGGACGTAGT GATGGTGGAA GAGGGGAAGA CTTTTCCTCG ATTTCTTTGC CT - #GAGGGATG69720- GAATTCAGGC TCCCCCAATA ACATATTCAT GGTCTTTCTC TGGTCAGTCA GT - #GATGTTCA69780- TAACACAAGC AAGCCTGTCA TCAGGACCAA TCTGTGATGG CTGAGACATC AG - #GTGCTCTT69840- CCAAAAGAGC CATAATTCAC CCTTCATTTC CCAAGGTTTT TTTTTTCTTG CT - #GTTATTAC69900- TGCTCTTTTA TCATGGTTAA TAAGTCTGAG GTGGCTTCAG ACAGCCAGTC CT - #AACCCCTG69960- AGTCAATCTG GGGCCTCTAA CAGGAAGCCA GACTGAAGTT CTGATAGATG GG - #TTTGAGTG70020- GCTGTGAACT GTGTTTCTGT AGCATCCAGA CTGATTTGCA CTGAAAGGGA GC - #TTCCATAT70080- TAGGGTACAA GGATGATCAA TATGTCTCCT GTTTATATTT GGTGGAAAAA GT - #TGTGGGAA70140- TCGTGCTTAA AGGATCTCAA CTTTGAAATT AAAAGTATAA CGTCCTAACA GA - #CATCCTCC70200- TTCTCTTTAG AAACACAAGG ATCCATTTTC AAGTAATTTC AAAAGAACTA TG - #TTGCTTTC70260- CCCACCCCTT CCCAAGTACA CTTATTATAA TATATCCAGT CCATTTGCTA GC - #TTTGTGTC70320- TTTAGAAAAG TTGCTTAACC TCTCTCTGTA AAATGGTGCT TATATTAGTA CT - #AACATTCA70380- GGGTTATTGT GAGGATTAAA TGAGGTAATT CATGTAATGA CTAGTTCTAT TT - #CTAGCACA70440- ATTTAAACCC TCAACAAATA TGAACTATTA TCACTGTCAT AGTTTTTGTT GT - #TGTTTTCT70500- AATTATATAA TCTTCAAGAT TCTGAGATGG GGGCTGTTGC TCTTTCCTTG AC - #TTGAACAT70560- CTTGGTCTTT TCCTAGGAGG AAACTTGACT CTTGAAATGG TCAAATCCAT TG - #TCCTAGTT70620- CATCCTGACC CCTCCCTGGC TCCAATCCCC ACCCCTTACC GTCCTCCACC CT - #TCCTACAT70680- TCCTGCACAG TTGGTCTTAT TTATTTTTCA GTCAACTAAG GGTGTTGTTA AA - #TCTTTTAT70740- TTTTCTGCTG CCCGATTTGG TTCTAAGCAC TCCACTCCCT ACGCTGCTCA TA - #ACAAGAAT70800- GCCTGGGAAC GCTCAGTCAG CCATATCCCT CCCCTGTCGG AACACCCAGT TC - #TTAATGCT70860- CCTGGAGAGG CAACATTTCT GAGGCCCCAC TGCCATAAGC CCCCCTCCCC CA - #TGAAGCCA70920- GTGGTCTGGT AGTAATGAAC CCCCAACGGC CCGGAGAAAA CTGGGGCAAG GT - #GTTTGTCT70980- GGGGAAATGT TGCATGTTGC CTTGACTGTG CTTTCTTCTA CAAAGCTTAA AA - #AGAGATAT71040- TATATTATTT TATTTTTATT TTTATTTTTG AGATGGAGTC TTACTTGGTT GC - #CCAGGCTG71100- GGTGTGCAGT GGCACAGTCA TGGCTCACTG CAACCTCCAC CTCCTGGGTT CA - #AGTGATTC71160- TCCTGCCTCA GCCTCCCAAG TAGCTGGGAC TACAGGCACA TGCCACCATG CC - #TGGCTAAT71220- TTGTATATTT TTAGTAGAGA CGGGGTTTCA CCATATTAAC TACATTGGTC TT - #GAACTCCT71280- GACCTCAAGT GATATGCCCG CCTCGGACTC CCAAAGTGCT GGGATTAAAA GC - #ATGAGCCA71340- CTGCGCCCGG CCAAAAAGAG ATATTCAAAA GCTCCCTCTG ACTGTGTGTG CT - #GAAGGCTG71400- AGTGCTGATG CCATTGCTTA ATTAATGTTG TTCATGATCT CCATTTGGGC GA - #TTTGTTTA71460- GCTCCTTGTG GCCCTTTTTG GACTTAGCTT ATCATGTGAC ATTGACAAAT TA - #ATGAGAAG71520- TGAGCATGTG ATGATGCTTG GATTAGGACA GAAATCACAT CTAGGACATC TC - #AGGCCCTT71580- TCCACCTGGG ACCTGAGACC TCAAATCTCT TGGCAGGAGA TGAGTGGGTC TA - #CACAGCCC71640- GATTTTGAGG TAGGTGTGGC TAGCCTCATT TATGCGATGG GAAAACTGTG GT - #CCGGGAAC71700- CAGGGGTTTT CAAATTATGC TTTTTGCCCA GGGCTGGATG TAGGATGTCT GG - #GGGAGAGG71760- CTTGACTGAG ATCTGGGTAC ACTGAGCCTC CACTTTAGGA GGTAACCTAG AG - #ACTACACC71820- TACTCCCTAA ACTGTATTGA CTTTTGGAAG TCAACCATTT AGAAGAGTGT GG - #TTTTGGTT71880- TCGATCGTAT CCCAGCAGTC TTTTCTCTGC CCTTGTTAAT CTGATTCATG AT - #CTGAACCT71940- GGGCTGGCTG GAGGCTGGCC ATGTCACTTT GCAGACCATG GACACCCCTG AG - #TGCCCTCA72000- CAGAACCAGC CAATGGAAAA GTACAACGTC TTCTGGCTTC TCAGCCTTGC CA - #TCTCCCTC72060- TGGCCTATTT GATACCCCCT TTTATATTGA GGGAGTGAAA ATGTAGCATC CA - #AACTGAAA72120- ACGCAGGTTT TTCTTTGGTT TTTATAGGAA AAACAAATTG GCATGAACAC TC - #AGTCAAAC72180- CAGCTCAGGC TGTTTGGGCA GATGCCTTTC TTTGCTTTTT TCTGTTTATT TT - #CCTACAAA72240- TCAATGCTTA ACTGCGTTGT TATCGGAGCA GAGCAACAGG TGCAAAAAAA TA - #ACTCTGCT72300- GCCAACTCAA ATGAAAAGGT AGGGCTTATA CCCTCTGGGA GGTATTCAGA AG - #ATAACAGA72360- AGCCCCTGCC AGCAACTGAA TTAACAGCTC TGTTTACGGT GGGTTTTATG TT - #AACAACCT72420- GCTCCTGACC CTCCTACACA TAAACACACC ATTGTCTCAG AGAGAGACAT TC - #AGCCATCC72480- AGACAACCCA CTGCTTTATT CTGCCCTGAG TGGAGATTGG TTTTGGCTCA GG - #CTGCTTTG72540- TGAAACTCAG AAGCATTATC CTCTCTGCCA ACTCCACGTC CTAGTCAGAG TT - #TTCTGTGA72600- AGGCAAGGGC ATGGGGTTGC CGGAGAGAAG AGGATTGGTC CTGCTTTTAA GC - #CTAGCTGA72660- AATTCTTTTC AAGGTTGGTC ATTCTCAAAT GCCAGAGAGG GTTGCCCGGC TC - #TCTCTGCT72720- CTTGCCCCAT TCCATTCACA ACAGGAGGTG GGGAATGAGC TCAGATGACT TT - #GGAAGGAG72780- CCACTATTAT TTTGGAAGCC GTGTCCTTGT GAATAGTCCA TCAGGGTAGG GC - #AGCGTCTA72840- TGTTTTGTTA ACTATTGTAT CGCCAGCACC TAGCAAAGTG CCCAGCATCT AG - #TAGACACT72900# 72928 ATTA CAGAGGGT- (2) INFORMATION FOR SEQ ID NO:2:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 5427 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:- ATTTATCTTC ACTCTGATGA GGGCTCAGAC TTGATAACGC CCGTGGTGCC CC - #ATCCCTAT 60- AGGAGCTGGT GAGATTGCAG CCTGCTGCCT CCCCTCCATC AGCCACAGCT AT - #TGGATTTC120- CCACCCAGAA TCTTTAGGTA AATGAGATCA TGATTCTGGA AGGAGGTGGT GT - #AATGAATC180- TCAACCCCGG CAACAACCTC CTTCACCAGC CGCCAGCCTG GACAGACAGC TA - #CTCCACGT240- GCAATGTTTC CAGTGGGTTT TTTGGAGGCC AGTGGCATGA AATTCATCCT CA - #GTACTGGA300- CCAAGTACCA GGTGTGGGAG TGGCTCCAGC ACCTCCTGGA CACCAACCAG CT - #GGATGCCA360- ATTGTATCCC TTTCCAAGAG TTCGACATCA ACGGCGAGCA CCTCTGCAGC AT - #GAGTTTGC420- AGGAGTTCAC CCGGGCGGCA GGGACGGCGG GGCAGCTCCT CTACAGCAAC TT - #GCAGCATC480- TGAAGTGGAA CGGCCAGTGC AGTAGTGACC TGTTCCAGTC CACACACAAT GT - #CATTGTCA540- AGACTGAACA AACTGAGCCT TCCATCATGA ACACCTGGAA AGACGAGAAC TA - #TTTATATG600- ACACCAACTA TGGTAGCACA GTAGATTTGT TGGACAGCAA AACTTTCTGC CG - #GGCTCAGA660- TCTCCATGAC AACCACCAGT CACCTTCCTG TTGCAGAGTC ACCTGATATG AA - #AAAGGAGC720- AAGACCCCCC TGCCAAGTGC CACACCAAAA AGCACAACCC GAGAGGGACT CA - #CTTATGGG780- AATTCATCCG CGACATCCTC TTGAACCCAG ACAAGAACCC AGGATTAATA AA - #ATGGGAAG840- ACCGATCTGA GGGCGTCTTC AGGTTCTTGA AATCAGAGGC AGTGGCTCAG CT - #ATGGGGTA900- AAAAGAAGAA CAACAGCAGC ATGACCTATG AAAAGCTCAG CCGAGCTATG AG - #ATATTACT960- ACAAAAGAGA AATACTGGAG CGTGTGGATG GACGAAGACT GGTATATAAA TT - #TGGGAAGA1020- ATGCCCGAGG ATGGAGAGAA AATGAAAACT GAAGCTGCCA ATACTTTGGA CA - #CAAACCAA1080- AACACACACC AAATAATCAG AAACAAAGAA CTCCTGGACG TAAATATTTC AA - #AGACTACT1140- TTTCTCTGAT ATTTATGTAC CATGAGGGGA AAAAGAAACT ACTTCTAACG GG - #AAGAAGAA1200- ACACTACAGT CGATTAAAAA AATTATTTTG TTACTTCGAA GTATGTCCTA TA - #TGGGGAAA1260- AAACGTACAC AGTTTTCTGT GAAATATGAT GCTGTATGTG GTTGTGATTT TT - #TTTCACCT1320- CTATTGTGAA TTCTTTTTCA CTGCAAGAGT AACAGGATTT GTAGCCTTGT GC - #TTCTTGCT1380- AAGAGAAAGA AAAACAAAAT CAGAGGGCAT TAAATGTTTT GTATGTGACA TG - #ATTTAGAA1440- AAAGGTGATG CATCCTCCTC ACATAAGCAT CCATATGGCT TCGTCAAGGG AG - #GTGAACAT1500- TGTTGCTGAG TTAAATTCCA GGGTCTCAGA TGGTTAGGAC AAAGTGGATG GA - #TGCCGGGA1560- AGTTTAACCT GAGCCTTAGG ATCCAATGAG TGGAGAATGG GGACTTCCAA AA - #CCCAAGGT1620- TGGCTATAAT CTCTGCATAA CCACATGACT TGGAATGCTT AAATCAGCAA GA - #AGAATAAT1680- GGTGGGGTCT TTATACTCAT TCAGGAATGG TTTATCTGAT GCCAGGGCTG TC - #TTCCTTTC1740- TCCCCTTTGG ATGGTTGGTG AAATACTTTA ATTGCCCTGT CTGCTCACTT CT - #AGCTATTT1800- AAGAGAGAAC CCAGCTTGGT TCTTTTTTGC TCCAAGTGCT TAAAAATAAG TT - #GGAAAAAG1860- GAGACGGTGG TGTGGAAATG GCTGAAGAGT TTGCTCTTGT ATCCCTATAG TC - #CAAGGTTT1920- CTCAATCTGC ACAATTGACA TTTTTGGCCG GAGTGTTCTT TGTGGTGAGG GC - #TTTCCTGT1980- GCATTGTAAG ATGTTCAGCA GTATCCACTC ATGGTCTCTA ACCACTTGAC AC - #CAGAAACC2040- CCCCAGCTGT GATAACGCAA AATGTCTCTA GACATCACCA AATGTTCCCT GG - #GGGTGGCA2100- AATTTGCCCT TGATTGAGAA CCACCAGTTT AGCTAGTCAA TATGAGGATG GT - #GGTTTATT2160- CTCAGAAGAA AAAGATATGT AAGGTCTTTT AGCTCCTTAG AGTGAAGCAA AA - #GCAAGACT2220- TCAACCTCAA CCTATCTTTA TGTTTTAAAT ATTAGGGACA ATAAGTTGAA AT - #AGCTAGAG2280- GAGCTTCTTT TCAGAACCCC AGATGAGAGC CAATGTCAGA TAAAGTAAGC AT - #AGCAATGT2340- AGCAGGAACT ACAATAGAAG ACATTTTCAC TGGAATTACA AAGCAGAATT AA - #AATTATAT2400- TGTAGAAGGA AACACCAAGA AAAGAATTTC CAGGGAAAAT CCTCTTTGCA GG - #TATTAATT2460- CTTATAATTT TTTGTCTTTT GGATTATCTG TTTACTGTCT CATCTGAACT GA - #TCCCAGGT2520- GAACGGTTTA TTGCCTAGAT TTGTACTCAG AGGAATTTTT TTTGTTTTGT TT - #TGTCTTTT2580- AAGAAAGGAA AGAAAGGATG AAAAAAATAA ACAGAAAACT CAGCTCAGGC AC - #AATTGTCA2640- CCAAGGAGTT AAAAGCTTCT TCTTCAATAG AGGAATTGTT CTGGGGGTCC TG - #GAGACTTA2700- CCATTGAGCC ATGCAATCTG GGAAGCACAG GAATAAGTAG ACACTTTGAA AA - #TGGATTTG2760- AATGTTCTCA TCCCTTTTGC AGCTTTTCTT TTTGGCTCTC TCATGTCCTT GG - #CTTGCTCC2820- TCTATTCTAC CTCTCTTTCT CCAGCAATAA TATGCAAATG AAGACATGTA TC - #CATAAGAA2880- GGAGTGCTCT TCATCAACTA ATAGAGCACC TACCACAGTG TCATACCTGG TA - #GAGGTGAG2940- CAATTCATAT TCAAAGGTTG CAAAGTGTTT GTAATATATT CATGAGGCTG GA - #AGTAAGAA3000- GAATTAAAAA TTTGTCCTAA TTACAATGAG AACCATTCTA GGTAGTGATC TT - #GGAGCACA3060- CATGAATAAC TTTCTGAAGG TGCAACCAAA TCCATTTTTA TTTCTGCCTG GC - #TTGGTCAC3120- CTCTGTAAAG GTTTAACTTA GTGTTGTCAA GTAACAGTTA CTGAAAGAGC TG - #AGAAAAAG3180- AACAATGAAC AGCAACGATC TTGACTGTGC AACTCAGACA TTCCTGCAGA AA - #AGACATAT3240- GTTGCTTTAC AAGAAGGCCA AAGAACTATG GGGCCTTCCC AGCATTTGAC TG - #TTCATTGC3300- ATAGAATGAA TTAAATATCC AGTTACTTGA ATGGGTATAA CGCATGAATA TT - #TGTGTGTC3360- TGTGTGTGTG TCTGAGTTGT GTGATTTTAT TAGGGGCATC TGCCAATTCT CT - #CACTGTGG3420- TTCCTTCTCT GACTTTGCCT GTTCATCATC TAAGGAGGCT AGATCCTTCG CT - #GACTTCAC3480- CATTCCTCAA ACCTGTAAGT TTCTCACTTC TTCCAAATTG GCTTTGGCTC TT - #TCTTCAAC3540- CTTTCCATTC AAGAGCAATC TTTGCTAAGG AGTAAGTGAA TGTGAAGAGT AC - #CAACTACA3600- ACAATTCTAC AGATAATTAG TGGATTGTGT TGTTTGTTGA GAGTGAAGGT TT - #CTTGGCAT3660- CTGGTGCCTG ATTAAGGCTT GAGTATTAAG TTCTCAGCAT ATCTCTCTAT TG - #TCTTGACT3720- TGAGTTTGCT GCATTTTCTA TGTGCTGTTC GTGACTTGGA GAACTTAAAG TA - #ATCGAGCT3780- ATGCCAACTT GGGGTGGTAA CAGAGTACTT CCCACCACAG TGTTGAAAGG GA - #GAGCAAAG3840- TCTTATGGAT AAACCCTCCT TTCTTTTGGG GACACATGGC TCTCACTTGA GA - #AGCTCACC3900- TGTGCTGAAT GTCCACATGG TCACTAAACA TGTTATCCTT AAACCCCCCG TA - #TGCCTGAG3960- TTGAAAGGGC TCTCTCTTAT TAGGTTTTCA TGGGAACATG AGGCAGCAAA TC - #TATTGCTA4020- AGACTTTACC AGGCTCAAAT CATCTGAGGC TGATAGATAT TTGACTTGGT AA - #GACTTAAG4080- TAAGGCTCTG GCTCCCAGGG GCATAAGCAA CAGTTTCTTG AATGTGCCAT CT - #GAGAAGGG4140- AGACCCAGGT TATGAGTTTT CCTTTGAACA CATTGGTCTT TTCTCAAAGT TC - #CTGCCTTG4200- CTAGACTGTT AGCTCTTTGA GGACAGGGAC TATGTCTTAT CAATCACTAT TA - #TTTTCCTG4260- TTACCTAGCA TGGGACAAGT ACACAACACA TATTTGTTCA ATGAATGAAT GA - #ATGTCTTC4320- TAAAAGACTC CTCTGATTGG GAGACCATAT CTATAATTGG GATGTGAATC AT - #TTCTTCAG4380- TGGAATAAGA GCACAACGGC ACAACCTTCA AGGACATATT ATCTACTATG AA - #CATTTTAC4440- TGTGAGACTC TTTATTTTGC CTTCTACTTG CGCTGAAATG AAACCAAAAC AG - #GCCGTTGG4500- GTTCCACAAG TCAATATATG TTGGATGAGG ATTCTGTTGC CTTATTGGGA AC - #TGTGAGAC4560- TTATCTGGTA TGAGAAGCCA GTAATAAACC TTTGACCTGT TTTAACCAAT GA - #AGATTATG4620- AATATGTTAA TATGATGTAA ATTGCTATTT AAGTGTAAAG CAGTTCTAAG TT - #TTAGTATT4680- TGGGGGATTG GTTTTTATTA TTTTTTTCCT TTTTGAAAAA TACTGAGGGA TC - #TTTTGATA4740- AAGTTAGTAA TGCATGTTAG ATTTTAGTTT TGCAAGCATG TTGTTTTTCA AA - #TATATCAA4800- GTATAGAAAA AGGTAAAACA GTTAAGAAGG AAGGCAATTA TATTATTCTT CT - #GTAGTTAA4860- GCAAACACTT GTTGAGTGCC TGCTATGTGC ACGGCATGGG CCCATATGTG TG - #AGGAGCTT4920- GTCTAATTAT GTAGGAAGCA ATAGATCTCG GTAGTTACGT ATTGGGCAGA TA - #CTTACTGT4980- ATGAATGAAA GAACATCACA GTAATCACAA TATCAGAGCT GAATTATCCT CA - #GTGTAGCT5040- TCTTGGAATT CAGTTTCTGG AACTAGAGAT AGAGCATTTA TTAAAAAAAA CT - #CCTGTTGA5100- GACTGTGTCT TATGAACCTC TGAAACGTAC AAGCCTTCAC AAGTTTAACT AA - #ATTGGGAT5160- TAATCTTTCT GTAGTTATCT GCATAATTCT TGTTTTTCTT TCCATCTGGC TC - #CTGGGTTG5220- ACAATTTGTG GAAACAACTC TATTGCTACT ATTTAAAAAA AATCAGAAAT CT - #TTCCCTTT5280- AAGCTATGTT AAATTCAAAC TATTCCTGCT ATTCCTGTTT TGTCAAAGAA TT - #ATATTTTT5340- CAAAATATGT TTATTTGTTT GATGGGTCCC AGGAAACACT AATAAAAACC AC - #AGAGACCA5400# 5427 AAAA AAAAAAA- (2) INFORMATION FOR SEQ ID NO:3:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 5510 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:- ATCGCTCTCT GGTAGAGTTG ACGTGACACT CATTTCTGTT GTGGGTGGGG CC - #CTGGTTGG 60- GAGGCATTGG CTCCACTGCA GCCTGGGTGT CTAGAGACCA CATTCTCACC CT - #GCCTTTGT120- TACTGGGAAA CCGAACGCGG CGCTGTGGCT TTCAGCTTGG GTAAGCCGGG TC - #TGCGGCGG180- GGATTGCCAT CTGAAGACAG AGGCAGGAGG GCAGCCACAC CTTGCCCAGA TC - #ATGATTCT240- GGAAGGAGGT GGTGTAATGA ATCTCAACCC CGGCAACAAC CTCCTTCACC AG - #CCGCCAGC300- CTGGACAGAC AGCTACTCCA CGTGCAATGT TTCCAGTGGG TTTTTTGGAG GC - #CAGTGGCA360- TGAAATTCAT CCTCAGTACT GGACCAAGTA CCAGGTGTGG GAGTGGCTCC AG - #CACCTCCT420- GGACACCAAC CAGCTGGATG CCAATTGTAT CCCTTTCCAA GAGTTCGACA TC - #AACGGCGA480- GCACCTCTGC AGCATGAGTT TGCAGGAGTT CACCCGGGCG GCAGGGACGG CG - #GGGCAGCT540- CCTCTACAGC AACTTGCAGC ATCTGAAGTG GAACGGCCAG TGCAGTAGTG AC - #CTGTTCCA600- GTCCACACAC AATGTCATTG TCAAGACTGA ACAAACTGAG CCTTCCATCA TG - #AACACCTG660- GAAAGACGAG AACTATTTAT ATGACACCAA CTATGGTAGC ACAGTAGATT TG - #TTGGACAG720- CAAAACTTTC TGCCGGGCTC AGATCTCCAT GACAACCACC AGTCACCTTC CT - #GTTGCAGA780- GTCACCTGAT ATGAAAAAGG AGCAAGACCC CCCTGCCAAG TGCCACACCA AA - #AAGCACAA840- CCCGAGAGGG ACTCACTTAT GGGAATTCAT CCGCGACATC CTCTTGAACC CA - #GACAAGAA900- CCCAGGATTA ATAAAATGGG AAGACCGATC TGAGGGCGTC TTCAGGTTCT TG - #AAATCAGA960- GGCAGTGGCT CAGCTATGGG GTAAAAAGAA GAACAACAGC AGCATGACCT AT - #GAAAAGCT1020- CAGCCGAGCT ATGAGATATT ACTACAAAAG AGAAATACTG GAGCGTGTGG AT - #GGACGAAG1080- ACTGGTATAT AAATTTGGGA AGAATGCCCG AGGATGGAGA GAAAATGAAA AC - #TGAAGCTG1140- CCAATACTTT GGACACAAAC CAAAACACAC ACCAAATAAT CAGAAACAAA GA - #ACTCCTGG1200- ACGTAAATAT TTCAAAGACT ACTTTTCTCT GATATTTATG TACCATGAGG GG - #AAAAAGAA1260- ACTACTTCTA ACGGGAAGAA GAAACACTAC AGTCGATTAA AAAAATTATT TT - #GTTACTTC1320- GAAGTATGTC CTATATGGGG AAAAAACGTA CACAGTTTTC TGTGAAATAT GA - #TGCTGTAT1380- GTGGTTGTGA TTTTTTTTCA CCTCTATTGT GAATTCTTTT TCACTGCAAG AG - #TAACAGGA1440- TTTGTAGCCT TGTGCTTCTT GCTAAGAGAA AGAAAAACAA AATCAGAGGG CA - #TTAAATGT1500- TTTGTATGTG ACATGATTTA GAAAAAGGTG ATGCATCCTC CTCACATAAG CA - #TCCATATG1560- GCTTCGTCAA GGGAGGTGAA CATTGTTGCT GAGTTAAATT CCAGGGTCTC AG - #ATGGTTAG1620- GACAAAGTGG ATGGATGCCG GGAAGTTTAA CCTGAGCCTT AGGATCCAAT GA - #GTGGAGAA1680- TGGGGACTTC CAAAACCCAA GGTTGGCTAT AATCTCTGCA TAACCACATG AC - #TTGGAATG1740- CTTAAATCAG CAAGAAGAAT AATGGTGGGG TCTTTATACT CATTCAGGAA TG - #GTTTATCT1800- GATGCCAGGG CTGTCTTCCT TTCTCCCCTT TGGATGGTTG GTGAAATACT TT - #AATTGCCC1860- TGTCTGCTCA CTTCTAGCTA TTTAAGAGAG AACCCAGCTT GGTTCTTTTT TG - #CTCCAAGT1920- GCTTAAAAAT AAGTTGGAAA AAGGAGACGG TGGTGTGGAA ATGGCTGAAG AG - #TTTGCTCT1980- TGTATCCCTA TAGTCCAAGG TTTCTCAATC TGCACAATTG ACATTTTTGG CC - #GGAGTGTT2040- CTTTGTGGTG AGGGCTTTCC TGTGCATTGT AAGATGTTCA GCAGTATCCA CT - #CATGGTCT2100- CTAACCACTT GACACCAGAA ACCCCCCAGC TGTGATAACG CAAAATGTCT CT - #AGACATCA2160- CCAAATGTTC CCTGGGGGTG GCAAATTTGC CCTTGATTGA GAACCACCAG TT - #TAGCTAGT2220- CAATATGAGG ATGGTGGTTT ATTCTCAGAA GAAAAAGATA TGTAAGGTCT TT - #TAGCTCCT2280- TAGAGTGAAG CAAAAGCAAG ACTTCAACCT CAACCTATCT TTATGTTTTA AA - #TATTAGGG2340- ACAATAAGTT GAAATAGCTA GAGGAGCTTC TTTTCAGAAC CCCAGATGAG AG - #CCAATGTC2400- AGATAAAGTA AGCATAGCAA TGTAGCAGGA ACTACAATAG AAGACATTTT CA - #CTGGAATT2460- ACAAAGCAGA ATTAAAATTA TATTGTAGAA GGAAACACCA AGAAAAGAAT TT - #CCAGGGAA2520- AATCCTCTTT GCAGGTATTA ATTCTTATAA TTTTTTGTCT TTTGGATTAT CT - #GTTTACTG2580- TCTCATCTGA ACTGATCCCA GGTGAACGGT TTATTGCCTA GATTTGTACT CA - #GAGGAATT2640- TTTTTTGTTT TGTTTTGTCT TTTAAGAAAG GAAAGAAAGG ATGAAAAAAA TA - #AACAGAAA2700- ACTCAGCTCA GGCACAATTG TCACCAAGGA GTTAAAAGCT TCTTCTTCAA TA - #GAGGAATT2760- GTTCTGGGGG TCCTGGAGAC TTACCATTGA GCCATGCAAT CTGGGAAGCA CA - #GGAATAAG2820- TAGACACTTT GAAAATGGAT TTGAATGTTC TCATCCCTTT TGCAGCTTTT CT - #TTTTGGCT2880- CTCTCATGTC CTTGGCTTGC TCCTCTATTC TACCTCTCTT TCTCCAGCAA TA - #ATATGCAA2940- ATGAAGACAT GTATCCATAA GAAGGAGTGC TCTTCATCAA CTAATAGAGC AC - #CTACCACA3000- GTGTCATACC TGGTAGAGGT GAGCAATTCA TATTCAAAGG TTGCAAAGTG TT - #TGTAATAT3060- ATTCATGAGG CTGGAAGTAA GAAGAATTAA AAATTTGTCC TAATTACAAT GA - #GAACCATT3120- CTAGGTAGTG ATCTTGGAGC ACACATGAAT AACTTTCTGA AGGTGCAACC AA - #ATCCATTT3180- TTATTTCTGC CTGGCTTGGT CACCTCTGTA AAGGTTTAAC TTAGTGTTGT CA - #AGTAACAG3240- TTACTGAAAG AGCTGAGAAA AAGAACAATG AACAGCAACG ATCTTGACTG TG - #CAACTCAG3300- ACATTCCTGC AGAAAAGACA TATGTTGCTT TACAAGAAGG CCAAAGAACT AT - #GGGGCCTT3360- CCCAGCATTT GACTGTTCAT TGCATAGAAT GAATTAAATA TCCAGTTACT TG - #AATGGGTA3420- TAACGCATGA ATATTTGTGT GTCTGTGTGT GTGTCTGAGT TGTGTGATTT TA - #TTAGGGGC3480- ATCTGCCAAT TCTCTCACTG TGGTTCCTTC TCTGACTTTG CCTGTTCATC AT - #CTAAGGAG3540- GCTAGATCCT TCGCTGACTT CACCATTCCT CAAACCTGTA AGTTTCTCAC TT - #CTTCCAAA3600- TTGGCTTTGG CTCTTTCTTC AACCTTTCCA TTCAAGAGCA ATCTTTGCTA AG - #GAGTAAGT3660- GAATGTGAAG AGTACCAACT ACAACAATTC TACAGATAAT TAGTGGATTG TG - #TTGTTTGT3720- TGAGAGTGAA GGTTTCTTGG CATCTGGTGC CTGATTAAGG CTTGAGTATT AA - #GTTCTCAG3780- CATATCTCTC TATTGTCTTG ACTTGAGTTT GCTGCATTTT CTATGTGCTG TT - #CGTGACTT3840- GGAGAACTTA AAGTAATCGA GCTATGCCAA CTTGGGGTGG TAACAGAGTA CT - #TCCCACCA3900- CAGTGTTGAA AGGGAGAGCA AAGTCTTATG GATAAACCCT CCTTTCTTTT GG - #GGACACAT3960- GGCTCTCACT TGAGAAGCTC ACCTGTGCTG AATGTCCACA TGGTCACTAA AC - #ATGTTATC4020- CTTAAACCCC CCGTATGCCT GAGTTGAAAG GGCTCTCTCT TATTAGGTTT TC - #ATGGGAAC4080- ATGAGGCAGC AAATCTATTG CTAAGACTTT ACCAGGCTCA AATCATCTGA GG - #CTGATAGA4140- TATTTGACTT GGTAAGACTT AAGTAAGGCT CTGGCTCCCA GGGGCATAAG CA - #ACAGTTTC4200- TTGAATGTGC CATCTGAGAA GGGAGACCCA GGTTATGAGT TTTCCTTTGA AC - #ACATTGGT4260- CTTTTCTCAA AGTTCCTGCC TTGCTAGACT GTTAGCTCTT TGAGGACAGG GA - #CTATGTCT4320- TATCAATCAC TATTATTTTC CTGTTACCTA GCATGGGACA AGTACACAAC AC - #ATATTTGT4380- TCAATGAATG AATGAATGTC TTCTAAAAGA CTCCTCTGAT TGGGAGACCA TA - #TCTATAAT4440- TGGGATGTGA ATCATTTCTT CAGTGGAATA AGAGCACAAC GGCACAACCT TC - #AAGGACAT4500- ATTATCTACT ATGAACATTT TACTGTGAGA CTCTTTATTT TGCCTTCTAC TT - #GCGCTGAA4560- ATGAAACCAA AACAGGCCGT TGGGTTCCAC AAGTCAATAT ATGTTGGATG AG - #GATTCTGT4620- TGCCTTATTG GGAACTGTGA GACTTATCTG GTATGAGAAG CCAGTAATAA AC - #CTTTGACC4680- TGTTTTAACC AATGAAGATT ATGAATATGT TAATATGATG TAAATTGCTA TT - #TAAGTGTA4740- AAGCAGTTCT AAGTTTTAGT ATTTGGGGGA TTGGTTTTTA TTATTTTTTT CC - #TTTTTGAA4800- AAATACTGAG GGATCTTTTG ATAAAGTTAG TAATGCATGT TAGATTTTAG TT - #TTGCAAGC4860- ATGTTGTTTT TCAAATATAT CAAGTATAGA AAAAGGTAAA ACAGTTAAGA AG - #GAAGGCAA4920- TTATATTATT CTTCTGTAGT TAAGCAAACA CTTGTTGAGT GCCTGCTATG TG - #CACGGCAT4980- GGGCCCATAT GTGTGAGGAG CTTGTCTAAT TATGTAGGAA GCAATAGATC TC - #GGTAGTTA5040- CGTATTGGGC AGATACTTAC TGTATGAATG AAAGAACATC ACAGTAATCA CA - #ATATCAGA5100- GCTGAATTAT CCTCAGTGTA GCTTCTTGGA ATTCAGTTTC TGGAACTAGA GA - #TAGAGCAT5160- TTATTAAAAA AAACTCCTGT TGAGACTGTG TCTTATGAAC CTCTGAAACG TA - #CAAGCCTT5220- CACAAGTTTA ACTAAATTGG GATTAATCTT TCTGTAGTTA TCTGCATAAT TC - #TTGTTTTT5280- CTTTCCATCT GGCTCCTGGG TTGACAATTT GTGGAAACAA CTCTATTGCT AC - #TATTTAAA5340- AAAAATCAGA AATCTTTCCC TTTAAGCTAT GTTAAATTCA AACTATTCCT GC - #TATTCCTG5400- TTTTGTCAAA GAATTATATT TTTCAAAATA TGTTTATTTG TTTGATGGGT CC - #CAGGAAAC5460# 5510ACAGAGA CCAGCCTGGA AAAAAAAAAA AAAAAAAAAA- (2) INFORMATION FOR SEQ ID NO:4:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 5667 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:- ATCGCTCTCT GGTAGAGTTG ACGTGACACT CATTTCTGTT GTGGGTGGGG CC - #CTGGTTGG 60- GAGGCATTGG CTCCACTGCA GCCTGGGTGT CTAGAGACCA CATTCTCACC CT - #GCCTTTGT120- TACTGGGAAA CCGAACGCGG CGCTGTGGCT TTCAGCTTGG GTAAGCCGGG TC - #TGCGGCGG180- GGATTGCCAT CTGAAGACAG AGGCAGGAGG GCAGCCACAC CTTGCCCAGC TG - #CACACCCA240- GTAACAAGTT TCCTCAGTGC GGGTATCTGC CACAGGCTGG GCTGGTCATC AA - #AGGGCCTC300- AGTCATATTT TAATAGAGCT CTTCAAGTAT CTGGCTTTGT GATAATATCA GG - #AATCAGTT360- GGTTTCTCTG ACAGACACTG CCCATTATCA TGATTCTGGA AGGAGGTGGT GT - #AATGAATC420- TCAACCCCGG CAACAACCTC CTTCACCAGC CGCCAGCCTG GACAGACAGC TA - #CTCCACGT480- GCAATGTTTC CAGTGGGTTT TTTGGAGGCC AGTGGCATGA AATTCATCCT CA - #GTACTGGA540- CCAAGTACCA GGTGTGGGAG TGGCTCCAGC ACCTCCTGGA CACCAACCAG CT - #GGATGCCA600- ATTGTATCCC TTTCCAAGAG TTCGACATCA ACGGCGAGCA CCTCTGCAGC AT - #GAGTTTGC660- AGGAGTTCAC CCGGGCGGCA GGGACGGCGG GGCAGCTCCT CTACAGCAAC TT - #GCAGCATC720- TGAAGTGGAA CGGCCAGTGC AGTAGTGACC TGTTCCAGTC CACACACAAT GT - #CATTGTCA780- AGACTGAACA AACTGAGCCT TCCATCATGA ACACCTGGAA AGACGAGAAC TA - #TTTATATG840- ACACCAACTA TGGTAGCACA GTAGATTTGT TGGACAGCAA AACTTTCTGC CG - #GGCTCAGA900- TCTCCATGAC AACCACCAGT CACCTTCCTG TTGCAGAGTC ACCTGATATG AA - #AAAGGAGC960- AAGACCCCCC TGCCAAGTGC CACACCAAAA AGCACAACCC GAGAGGGACT CA - #CTTATGGG1020- AATTCATCCG CGACATCCTC TTGAACCCAG ACAAGAACCC AGGATTAATA AA - #ATGGGAAG1080- ACCGATCTGA GGGCGTCTTC AGGTTCTTGA AATCAGAGGC AGTGGCTCAG CT - #ATGGGGTA1140- AAAAGAAGAA CAACAGCAGC ATGACCTATG AAAAGCTCAG CCGAGCTATG AG - #ATATTACT1200- ACAAAAGAGA AATACTGGAG CGTGTGGATG GACGAAGACT GGTATATAAA TT - #TGGGAAGA1260- ATGCCCGAGG ATGGAGAGAA AATGAAAACT GAAGCTGCCA ATACTTTGGA CA - #CAAACCAA1320- AACACACACC AAATAATCAG AAACAAAGAA CTCCTGGACG TAAATATTTC AA - #AGACTACT1380- TTTCTCTGAT ATTTATGTAC CATGAGGGGA AAAAGAAACT ACTTCTAACG GG - #AAGAAGAA1440- ACACTACAGT CGATTAAAAA AATTATTTTG TTACTTCGAA GTATGTCCTA TA - #TGGGGAAA1500- AAACGTACAC AGTTTTCTGT GAAATATGAT GCTGTATGTG GTTGTGATTT TT - #TTTCACCT1560- CTATTGTGAA TTCTTTTTCA CTGCAAGAGT AACAGGATTT GTAGCCTTGT GC - #TTCTTGCT1620- AAGAGAAAGA AAAACAAAAT CAGAGGGCAT TAAATGTTTT GTATGTGACA TG - #ATTTAGAA1680- AAAGGTGATG CATCCTCCTC ACATAAGCAT CCATATGGCT TCGTCAAGGG AG - #GTGAACAT1740- TGTTGCTGAG TTAAATTCCA GGGTCTCAGA TGGTTAGGAC AAAGTGGATG GA - #TGCCGGGA1800- AGTTTAACCT GAGCCTTAGG ATCCAATGAG TGGAGAATGG GGACTTCCAA AA - #CCCAAGGT1860- TGGCTATAAT CTCTGCATAA CCACATGACT TGGAATGCTT AAATCAGCAA GA - #AGAATAAT1920- GGTGGGGTCT TTATACTCAT TCAGGAATGG TTTATCTGAT GCCAGGGCTG TC - #TTCCTTTC1980- TCCCCTTTGG ATGGTTGGTG AAATACTTTA ATTGCCCTGT CTGCTCACTT CT - #AGCTATTT2040- AAGAGAGAAC CCAGCTTGGT TCTTTTTTGC TCCAAGTGCT TAAAAATAAG TT - #GGAAAAAG2100- GAGACGGTGG TGTGGAAATG GCTGAAGAGT TTGCTCTTGT ATCCCTATAG TC - #CAAGGTTT2160- CTCAATCTGC ACAATTGACA TTTTTGGCCG GAGTGTTCTT TGTGGTGAGG GC - #TTTCCTGT2220- GCATTGTAAG ATGTTCAGCA GTATCCACTC ATGGTCTCTA ACCACTTGAC AC - #CAGAAACC2280- CCCCAGCTGT GATAACGCAA AATGTCTCTA GACATCACCA AATGTTCCCT GG - #GGGTGGCA2340- AATTTGCCCT TGATTGAGAA CCACCAGTTT AGCTAGTCAA TATGAGGATG GT - #GGTTTATT2400- CTCAGAAGAA AAAGATATGT AAGGTCTTTT AGCTCCTTAG AGTGAAGCAA AA - #GCAAGACT2460- TCAACCTCAA CCTATCTTTA TGTTTTAAAT ATTAGGGACA ATAAGTTGAA AT - #AGCTAGAG2520- GAGCTTCTTT TCAGAACCCC AGATGAGAGC CAATGTCAGA TAAAGTAAGC AT - #AGCAATGT2580- AGCAGGAACT ACAATAGAAG ACATTTTCAC TGGAATTACA AAGCAGAATT AA - #AATTATAT2640- TGTAGAAGGA AACACCAAGA AAAGAATTTC CAGGGAAAAT CCTCTTTGCA GG - #TATTAATT2700- CTTATAATTT TTTGTCTTTT GGATTATCTG TTTACTGTCT CATCTGAACT GA - #TCCCAGGT2760- GAACGGTTTA TTGCCTAGAT TTGTACTCAG AGGAATTTTT TTTGTTTTGT TT - #TGTCTTTT2820- AAGAAAGGAA AGAAAGGATG AAAAAAATAA ACAGAAAACT CAGCTCAGGC AC - #AATTGTCA2880- CCAAGGAGTT AAAAGCTTCT TCTTCAATAG AGGAATTGTT CTGGGGGTCC TG - #GAGACTTA2940- CCATTGAGCC ATGCAATCTG GGAAGCACAG GAATAAGTAG ACACTTTGAA AA - #TGGATTTG3000- AATGTTCTCA TCCCTTTTGC AGCTTTTCTT TTTGGCTCTC TCATGTCCTT GG - #CTTGCTCC3060- TCTATTCTAC CTCTCTTTCT CCAGCAATAA TATGCAAATG AAGACATGTA TC - #CATAAGAA3120- GGAGTGCTCT TCATCAACTA ATAGAGCACC TACCACAGTG TCATACCTGG TA - #GAGGTGAG3180- CAATTCATAT TCAAAGGTTG CAAAGTGTTT GTAATATATT CATGAGGCTG GA - #AGTAAGAA3240- GAATTAAAAA TTTGTCCTAA TTACAATGAG AACCATTCTA GGTAGTGATC TT - #GGAGCACA3300- CATGAATAAC TTTCTGAAGG TGCAACCAAA TCCATTTTTA TTTCTGCCTG GC - #TTGGTCAC3360- CTCTGTAAAG GTTTAACTTA GTGTTGTCAA GTAACAGTTA CTGAAAGAGC TG - #AGAAAAAG3420- AACAATGAAC AGCAACGATC TTGACTGTGC AACTCAGACA TTCCTGCAGA AA - #AGACATAT3480- GTTGCTTTAC AAGAAGGCCA AAGAACTATG GGGCCTTCCC AGCATTTGAC TG - #TTCATTGC3540- ATAGAATGAA TTAAATATCC AGTTACTTGA ATGGGTATAA CGCATGAATA TT - #TGTGTGTC3600- TGTGTGTGTG TCTGAGTTGT GTGATTTTAT TAGGGGCATC TGCCAATTCT CT - #CACTGTGG3660- TTCCTTCTCT GACTTTGCCT GTTCATCATC TAAGGAGGCT AGATCCTTCG CT - #GACTTCAC3720- CATTCCTCAA ACCTGTAAGT TTCTCACTTC TTCCAAATTG GCTTTGGCTC TT - #TCTTCAAC3780- CTTTCCATTC AAGAGCAATC TTTGCTAAGG AGTAAGTGAA TGTGAAGAGT AC - #CAACTACA3840- ACAATTCTAC AGATAATTAG TGGATTGTGT TGTTTGTTGA GAGTGAAGGT TT - #CTTGGCAT3900- CTGGTGCCTG ATTAAGGCTT GAGTATTAAG TTCTCAGCAT ATCTCTCTAT TG - #TCTTGACT3960- TGAGTTTGCT GCATTTTCTA TGTGCTGTTC GTGACTTGGA GAACTTAAAG TA - #ATCGAGCT4020- ATGCCAACTT GGGGTGGTAA CAGAGTACTT CCCACCACAG TGTTGAAAGG GA - #GAGCAAAG4080- TCTTATGGAT AAACCCTCCT TTCTTTTGGG GACACATGGC TCTCACTTGA GA - #AGCTCACC4140- TGTGCTGAAT GTCCACATGG TCACTAAACA TGTTATCCTT AAACCCCCCG TA - #TGCCTGAG4200- TTGAAAGGGC TCTCTCTTAT TAGGTTTTCA TGGGAACATG AGGCAGCAAA TC - #TATTGCTA4260- AGACTTTACC AGGCTCAAAT CATCTGAGGC TGATAGATAT TTGACTTGGT AA - #GACTTAAG4320- TAAGGCTCTG GCTCCCAGGG GCATAAGCAA CAGTTTCTTG AATGTGCCAT CT - #GAGAAGGG4380- AGACCCAGGT TATGAGTTTT CCTTTGAACA CATTGGTCTT TTCTCAAAGT TC - #CTGCCTTG4440- CTAGACTGTT AGCTCTTTGA GGACAGGGAC TATGTCTTAT CAATCACTAT TA - #TTTTCCTG4500- TTACCTAGCA TGGGACAAGT ACACAACACA TATTTGTTCA ATGAATGAAT GA - #ATGTCTTC4560- TAAAAGACTC CTCTGATTGG GAGACCATAT CTATAATTGG GATGTGAATC AT - #TTCTTCAG4620- TGGAATAAGA GCACAACGGC ACAACCTTCA AGGACATATT ATCTACTATG AA - #CATTTTAC4680- TGTGAGACTC TTTATTTTGC CTTCTACTTG CGCTGAAATG AAACCAAAAC AG - #GCCGTTGG4740- GTTCCACAAG TCAATATATG TTGGATGAGG ATTCTGTTGC CTTATTGGGA AC - #TGTGAGAC4800- TTATCTGGTA TGAGAAGCCA GTAATAAACC TTTGACCTGT TTTAACCAAT GA - #AGATTATG4860- AATATGTTAA TATGATGTAA ATTGCTATTT AAGTGTAAAG CAGTTCTAAG TT - #TTAGTATT4920- TGGGGGATTG GTTTTTATTA TTTTTTTCCT TTTTGAAAAA TACTGAGGGA TC - #TTTTGATA4980- AAGTTAGTAA TGCATGTTAG ATTTTAGTTT TGCAAGCATG TTGTTTTTCA AA - #TATATCAA5040- GTATAGAAAA AGGTAAAACA GTTAAGAAGG AAGGCAATTA TATTATTCTT CT - #GTAGTTAA5100- GCAAACACTT GTTGAGTGCC TGCTATGTGC ACGGCATGGG CCCATATGTG TG - #AGGAGCTT5160- GTCTAATTAT GTAGGAAGCA ATAGATCTCG GTAGTTACGT ATTGGGCAGA TA - #CTTACTGT5220- ATGAATGAAA GAACATCACA GTAATCACAA TATCAGAGCT GAATTATCCT CA - #GTGTAGCT5280- TCTTGGAATT CAGTTTCTGG AACTAGAGAT AGAGCATTTA TTAAAAAAAA CT - #CCTGTTGA5340- GACTGTGTCT TATGAACCTC TGAAACGTAC AAGCCTTCAC AAGTTTAACT AA - #ATTGGGAT5400- TAATCTTTCT GTAGTTATCT GCATAATTCT TGTTTTTCTT TCCATCTGGC TC - #CTGGGTTG5460- ACAATTTGTG GAAACAACTC TATTGCTACT ATTTAAAAAA AATCAGAAAT CT - #TTCCCTTT5520- AAGCTATGTT AAATTCAAAC TATTCCTGCT ATTCCTGTTT TGTCAAAGAA TT - #ATATTTTT5580- CAAAATATGT TTATTTGTTT GATGGGTCCC AGGAAACACT AATAAAAACC AC - #AGAGACCA5640# 5667 AAAA AAAAAAA- (2) INFORMATION FOR SEQ ID NO:5:- (i) SEQUENCE CHARACTERISTICS:#acids (A) LENGTH: 300 amino (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: protein- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:- Met Ile Leu Glu Gly Gly Gly Val Met Asn Le - #u Asn Pro Gly Asn Asn# 15- Leu Leu His Gln Pro Pro Ala Trp Thr Asp Se - #r Tyr Ser Thr Cys Asn# 30- Val Ser Ser Gly Phe Phe Gly Gly Gln Trp Hi - #s Glu Ile His Pro Gln# 45- Tyr Trp Thr Lys Tyr Gln Val Trp Glu Trp Le - #u Gln His Leu Leu Asp# 60- Thr Asn Gln Leu Asp Ala Asn Cys Ile Pro Ph - #e Gln Glu Phe Asp Ile#80- Asn Gly Glu His Leu Cys Ser Met Ser Leu Gl - #n Glu Phe Thr Arg Ala# 95- Ala Gly Thr Ala Gly Gln Leu Leu Tyr Ser As - #n Leu Gln His Leu Lys# 110- Trp Asn Gly Gln Cys Ser Ser Asp Leu Phe Gl - #n Ser Thr His Asn Val# 125- Ile Val Lys Thr Glu Gln Thr Glu Pro Ser Il - #e Met Asn Thr Trp Lys# 140- Asp Glu Asn Tyr Leu Tyr Asp Thr Asn Tyr Gl - #y Ser Thr Val Asp Leu145 1 - #50 1 - #55 1 -#60- Leu Asp Ser Lys Thr Phe Cys Arg Ala Gln Il - #e Ser Met Thr Thr Thr# 175- Ser His Leu Pro Val Ala Glu Ser Pro Asp Me - #t Lys Lys Glu Gln Asp# 190- Pro Pro Ala Lys Cys His Thr Lys Lys His As - #n Pro Arg Gly Thr His# 205- Leu Trp Glu Phe Ile Arg Asp Ile Leu Leu As - #n Pro Asp Lys Asn Pro# 220- Gly Leu Ile Lys Trp Glu Asp Arg Ser Glu Gl - #y Val Phe Arg Phe Leu225 2 - #30 2 - #35 2 -#40- Lys Ser Glu Ala Val Ala Gln Leu Trp Gly Ly - #s Lys Lys Asn Asn Ser# 255- Ser Met Thr Tyr Glu Lys Leu Ser Arg Ala Me - #t Arg Tyr Tyr Tyr Lys# 270- Arg Glu Ile Leu Glu Arg Val Asp Gly Arg Ar - #g Leu Val Tyr Lys Phe# 285- Gly Lys Asn Ala Arg Gly Trp Arg Glu Asn Gl - #u Asn# 300- (2) INFORMATION FOR SEQ ID NO:6:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 2428 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:- CAGGGGTGCC GGGTTGCTCA GGCCATGGGA GCCACACCTG TTATTGCTGC CT - #CTGATTTG 60- TGTGACACTG AGAAGCCCAC AGGCCTGTCC CTCCAACTCG GTGGACCCTC TC - #TGTGTGCA120- TTTGGTGTGT GAGCCAGCTC TGAGAAGGGT TCAGAAGCCA CTGGAGGCAT CT - #GGGGACCT180- CAGCTTCCAT GCCATCTCTG CCTCACTCCC ACAGGGTAAT GTTGGACTCG GT - #GACACACA240- GCACCTTCCT GCCTAATGCA TCCTTCTGCG ATCCCCTGAT GTCGTGGACT GA - #TCTGTTCA300- GCAATGAAGA GTACTACCCT GCCTTTGAGC ATCAGACAGC CTGTGACTCA TA - #CTGGACAT360- CAGTCCACCC TGAATACTGG ACTAAGCGCC ATGTGTGGGA GTGGCTCCAG TT - #CTGCTGCG420- ACCAGTACAA GTTGGACACC AATTGCATCT CCTTCTGCAA CTTCAACATC AG - #TGGCCTGC480- AGCTGTGCAG CATGACACAG GAGGAGTTCG TCGAGGCAGC TGGCCTCTGC GG - #CGAGTACC540- TGTACTTCAT CCTCCAGAAC ATCCGCACAC AAGGTTACTC CTTTTTTAAT GA - #CGCTGAAG600- AAAGCAAGGC CACCATCAAA GACTATGCTG ATTCCAACTG CTTGAAAACA AG - #TGGCATCA660- AAAGTCAAGA CTGTCACAGT CATAGTAGAA CAAGCCTCCA AAGTTCTCAT CT - #ATGGGAAT720- TTGTACGAGA CCTGCTTCTA TCTCCTGAAG AAAACTGTGG CATTCTGGAA TG - #GGAAGATA780- GGGAACAAGG AATTTTTCGG GTGGTTAAAT CGGAAGCCCT GGCAAAGATG TG - #GGGACAAA840- GGAAGAAAAA TGACAGAATG ACGTATGAAA AGTTGAGCAG AGCCCTGAGA TA - #CTACTATA900- AAACAGGAAT TTTGGAGCGG GTTGACCGAA GGTTAGTGTA CAAATTTGGA AA - #AAATGCAC960- ACGGGTGGCA GGAAGACAAG CTATGATCTG CTCCAGGCAT CAAGCTCATT TT - #ATGGATTT1020- CTGTCTTTTA AAACAATCAG ATTGCAATAG ACATTCGAAA GGCTTCATTT TC - #TTCTCTTT1080- TTTTTTAACC TGCAAACATG CTGATAAAAT TTCTCCACAT CTCAGCTTAC AT - #TTGGATTC1140- AGAGTTGTTG TCTACGGAGG GTGAGAGCAG AAACTCTTAA GAAATCCTTT CT - #TCTCCCTA1200- AGGGGATGAG GGGATGATCT TTTGTGGTGT CTTGATCAAA CTTTATTTTC CT - #AGAGTTGT1260- GGAATGACAA CAGCCCATGC CATTGATGCT GATCAGAGAA AAACTATTCA AT - #TCTGCCAT1320- TAGAGACACA TCCAATGCTC CCATCCCAAA GGTTCAAAAG TTTTCAAATA AC - #TGTGGCAG1380- CTCACCAAAG GTGGGGGAAA GCATGATTAG TTTGCAGGTT ATGGTAGGAG AG - #GGTGAGAT1440- ATAAGACATA CATACTTTAG ATTTTAAATT ATTAAAGTCA AAAATCCATA GA - #AAAGTATC1500- CCTTTTTTTT TTTTTTGAGA CGGGTTCTCA CTATGTTGCC CAGGGCTGGT CT - #TGAACTCC1560- TATGCTCAAG TGATCCTCCC ACCTCGGCCT CCCAAAGTAC TGTGATTACA AG - #CGTGAGCC1620- ACGGCACCTG GGCAGAAAAG TATCTTAATT AATGAAAGAG CTAAGCCATC AA - #GCTGGGAC1680- TTAATTGGAT TTAACATAGG TTCACAGAAA GTTTCCTAAC CAGAGCATCT TT - #TTGACCAC1740- TCAGCAAAAC TTCCACAGAC ATCCTTCTGG ACTTAAACAC TTAACATTAA CC - #ACATTATT1800- AATTGTTGCT GAGTTTATTC CCCCTTCTAA CTGATGGCTG GCATCTGATA TG - #CAGAGTTA1860- GTCAACAGAC ACTGGCATCA ATTACAAAAT CACTGCTGTT TCTGTGATTC AA - #GCTGTCAA1920- CACAATAAAA TCGAAATTCA TTGATTCCAT CTCTGGTCCA GATGTTAAAC GT - #TTATAAAA1980- CCGGAAATGT CCTAACAACT CTGTAATGGC AAATTAAATT GTGTGTCTTT TT - #TGTTTTGT2040- CTTTCTACCT GATGTGTATT CAAGCGCTAT AACACGTATT TCCTTGACAA AA - #ATAGTGAC2100- AGTGAATTCA CACTAATAAA TGTTCATAGG TTAAAGTCTG CACTGACATT TT - #CTCATCAA2160- TCACTGGTAT GTAAGTTATC AGTGACTGAC AGCTAGGTGG ACTGCCCCTA GG - #ACTTCTGT2220- TTCACCAGAG CAGGAATCAA GTGGTGAGGC ACTGAATCGC TGTACAGGCT GA - #AGACCTCC2280- TTATTAGAGT TGAACTTCAA AGTAACTTGT TTTAAAAAAT GTGAATTACT GT - #AAAATAAT2340- CTATTTTGGA TTCATGTGTT TTCCAGGTGG ATATAGTTTG TAAACAATGT GA - #ATAAAGTA2400# 2428 AAAA AAAAAAAA- (2) INFORMATION FOR SEQ ID NO:7:- (i) SEQUENCE CHARACTERISTICS:#acids (A) LENGTH: 265 amino (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: protein- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:- Met Pro Ser Leu Pro His Ser His Arg Val Me - #t Leu Asp Ser Val Thr# 15- His Ser Thr Phe Leu Pro Asn Ala Ser Phe Cy - #s Asp Pro Leu Met Ser# 30- Trp Thr Asp Leu Phe Ser Asn Glu Glu Tyr Ty - #r Pro Ala Phe Glu His# 45- Gln Thr Ala Cys Asp Ser Tyr Trp Thr Ser Va - #l His Pro Glu Tyr Trp# 60- Thr Lys Arg His Val Trp Glu Trp Leu Gln Ph - #e Cys Cys Asp Gln Tyr#80- Lys Leu Asp Thr Asn Cys Ile Ser Phe Cys As - #n Phe Asn Ile Ser Gly# 95- Leu Gln Leu Cys Ser Met Thr Gln Glu Glu Ph - #e Val Glu Ala Ala Gly# 110- Leu Cys Gly Glu Tyr Leu Tyr Phe Ile Leu Gl - #n Asn Ile Arg Thr Gln# 125- Gly Tyr Ser Phe Phe Asn Asp Ala Glu Glu Se - #r Lys Ala Thr Ile Lys# 140- Asp Tyr Ala Asp Ser Asn Cys Leu Lys Thr Se - #r Gly Ile Lys Ser Gln145 1 - #50 1 - #55 1 -#60- Asp Cys His Ser His Ser Arg Thr Ser Leu Gl - #n Ser Ser His Leu Trp# 175- Glu Phe Val Arg Asp Leu Leu Leu Ser Pro Gl - #u Glu Asn Cys Gly Ile# 190- Leu Glu Trp Glu Asp Arg Glu Gln Gly Ile Ph - #e Arg Val Val Lys Ser# 205- Glu Ala Leu Ala Lys Met Trp Gly Gln Arg Ly - #s Lys Asn Asp Arg Met# 220- Thr Tyr Glu Lys Leu Ser Arg Ala Leu Arg Ty - #r Tyr Tyr Lys Thr Gly225 2 - #30 2 - #35 2 -#40- Ile Leu Glu Arg Val Asp Arg Arg Leu Val Ty - #r Lys Phe Gly Lys Asn# 255- Ala His Gly Trp Gln Glu Asp Lys Leu# 265- (2) INFORMATION FOR SEQ ID NO:8:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 2280 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:- CTGGGAGCGC CTGCCTTCTC TTGCCTTGAA AGCCTCCTCT TTGGACCTAG CC - #ACCGCTGC 60- CCTCACGGTA ATGTTGGACT CGGTGACACA CAGCACCTTC CTGCCTAATG CA - #TCCTTCTG120- CGATCCCCTG ATGTCGTGGA CTGATCTGTT CAGCAATGAA GAGTACTACC CT - #GCCTTTGA180- GCATCAGACA GCCTGTGACT CATACTGGAC ATCAGTCCAC CCTGAATACT GG - #ACTAAGCG240- CCATGTGTGG GAGTGGCTCC AGTTCTGCTG CGACCAGTAC AAGTTGGACA CC - #AATTGCAT300- CTCCTTCTGC AACTTCAACA TCAGTGGCCT GCAGCTGTGC AGCATGACAC AG - #GAGGAGTT360- CGTCGAGGCA GCTGGCCTCT GCGGCGAGTA CCTGTACTTC ATCCTCCAGA AC - #ATCCGCAC420- ACAAGGTTAC TCCTTTTTTA ATGACGCTGA AGAAAGCAAG GCCACCATCA AA - #GACTATGC480- TGATTCCAAC TGCTTGAAAA CAAGTGGCAT CAAAAGTCAA GACTGTCACA GT - #CATAGTAG540- AACAAGCCTC CAAAGTTCTC ATCTATGGGA ATTTGTACGA GACCTGCTTC TA - #TCTCCTGA600- AGAAAACTGT GGCATTCTGG AATGGGAAGA TAGGGAACAA GGAATTTTTC GG - #GTGGTTAA660- ATCGGAAGCC CTGGCAAAGA TGTGGGGACA AAGGAAGAAA AATGACAGAA TG - #ACGTATGA720- AAAGTTGAGC AGAGCCCTGA GATACTACTA TAAAACAGGA ATTTTGGAGC GG - #GTTGACCG780- AAGGTTAGTG TACAAATTTG GAAAAAATGC ACACGGGTGG CAGGAAGACA AG - #CTATGATC840- TGCTCCAGGC ATCAAGCTCA TTTTATGGAT TTCTGTCTTT TAAAACAATC AG - #ATTGCAAT900- AGACATTCGA AAGGCTTCAT TTTCTTCTCT TTTTTTTTAA CCTGCAAACA TG - #CTGATAAA960- ATTTCTCCAC ATCTCAGCTT ACATTTGGAT TCAGAGTTGT TGTCTACGGA GG - #GTGAGAGC1020- AGAAACTCTT AAGAAATCCT TTCTTCTCCC TAAGGGGATG AGGGGATGAT CT - #TTTGTGGT1080- GTCTTGATCA AACTTTATTT TCCTAGAGTT GTGGAATGAC AACAGCCCAT GC - #CATTGATG1140- CTGATCAGAG AAAAACTATT CAATTCTGCC ATTAGAGACA CATCCAATGC TC - #CCATCCCA1200- AAGGTTCAAA AGTTTTCAAA TAACTGTGGC AGCTCACCAA AGGTGGGGGA AA - #GCATGATT1260- AGTTTGCAGG TTATGGTAGG AGAGGGTGAG ATATAAGACA TACATACTTT AG - #ATTTTAAA1320- TTATTAAAGT CAAAAATCCA TAGAAAAGTA TCCCTTTTTT TTTTTTTTGA GA - #CGGGTTCT1380- CACTATGTTG CCCAGGGCTG GTCTTGAACT CCTATGCTCA AGTGATCCTC CC - #ACCTCGGC1440- CTCCCAAAGT ACTGTGATTA CAAGCGTGAG CCACGGCACC TGGGCAGAAA AG - #TATCTTAA1500- TTAATGAAAG AGCTAAGCCA TCAAGCTGGG ACTTAATTGG ATTTAACATA GG - #TTCACAGA1560- AAGTTTCCTA ACCAGAGCAT CTTTTTGACC ACTCAGCAAA ACTTCCACAG AC - #ATCCTTCT1620- GGACTTAAAC ACTTAACATT AACCACATTA TTAATTGTTG CTGAGTTTAT TC - #CCCCTTCT1680- AACTGATGGC TGGCATCTGA TATGCAGAGT TAGTCAACAG ACACTGGCAT CA - #ATTACAAA1740- ATCACTGCTG TTTCTGTGAT TCAAGCTGTC AACACAATAA AATCGAAATT CA - #TTGATTCC1800- ATCTCTGGTC CAGATGTTAA ACGTTTATAA AACCGGAAAT GTCCTAACAA CT - #CTGTAATG1860- GCAAATTAAA TTGTGTGTCT TTTTTGTTTT GTCTTTCTAC CTGATGTGTA TT - #CAAGCGCT1920- ATAACACGTA TTTCCTTGAC AAAAATAGTG ACAGTGAATT CACACTAATA AA - #TGTTCATA1980- GGTTAAAGTC TGCACTGACA TTTTCTCATC AATCACTGGT ATGTAAGTTA TC - #AGTGACTG2040- ACAGCTAGGT GGACTGCCCC TAGGACTTCT GTTTCACCAG AGCAGGAATC AA - #GTGGTGAG2100- GCACTGAATC GCTGTACAGG CTGAAGACCT CCTTATTAGA GTTGAACTTC AA - #AGTAACTT2160- GTTTTAAAAA ATGTGAATTA CTGTAAAATA ATCTATTTTG GATTCATGTG TT - #TTCCAGGT2220- GGATATAGTT TGTAAACAAT GTGAATAAAG TATTTAACAT GTTCAAAAAA AA - #AAAAAAAA2280- (2) INFORMATION FOR SEQ ID NO:9:- (i) SEQUENCE CHARACTERISTICS:#acids (A) LENGTH: 255 amino (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: protein- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:- Met Leu Asp Ser Val Thr His Ser Thr Phe Le - #u Pro Asn Ala Ser Phe# 15- Cys Asp Pro Leu Met Ser Trp Thr Asp Leu Ph - #e Ser Asn Glu Glu Tyr# 30- Tyr Pro Ala Phe Glu His Gln Thr Ala Cys As - #p Ser Tyr Trp Thr Ser# 45- Val His Pro Glu Tyr Trp Thr Lys Arg His Va - #l Trp Glu Trp Leu Gln# 60- Phe Cys Cys Asp Gln Tyr Lys Leu Asp Thr As - #n Cys Ile Ser Phe Cys#80- Asn Phe Asn Ile Ser Gly Leu Gln Leu Cys Se - #r Met Thr Gln Glu Glu# 95- Phe Val Glu Ala Ala Gly Leu Cys Gly Glu Ty - #r Leu Tyr Phe Ile Leu# 110- Gln Asn Ile Arg Thr Gln Gly Tyr Ser Phe Ph - #e Asn Asp Ala Glu Glu# 125- Ser Lys Ala Thr Ile Lys Asp Tyr Ala Asp Se - #r Asn Cys Leu Lys Thr# 140- Ser Gly Ile Lys Ser Gln Asp Cys His Ser Hi - #s Ser Arg Thr Ser Leu145 1 - #50 1 - #55 1 -#60- Gln Ser Ser His Leu Trp Glu Phe Val Arg As - #p Leu Leu Leu Ser Pro# 175- Glu Glu Asn Cys Gly Ile Leu Glu Trp Glu As - #p Arg Glu Gln Gly Ile# 190- Phe Arg Val Val Lys Ser Glu Ala Leu Ala Ly - #s Met Trp Gly Gln Arg# 205- Lys Lys Asn Asp Arg Met Thr Tyr Glu Lys Le - #u Ser Arg Ala Leu Arg# 220- Tyr Tyr Tyr Lys Thr Gly Ile Leu Glu Arg Va - #l Asp Arg Arg Leu Val225 2 - #30 2 - #35 2 -#40- Tyr Lys Phe Gly Lys Asn Ala His Gly Trp Gl - #n Glu Asp Lys Leu# 255- (2) INFORMATION FOR SEQ ID NO:10:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 2498 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:- GAGGGGCTGA CAGCGGCGTC CCTCGTCTGG GCAGCCTCCG CTCTGCCACT CT - #CCTCCCGT 60- CCTGAGGATG GGACCCCCGG AAAAGCGGCC TCTGGAGGCC TGCCATGGCA CC - #CAGAGCAG120- CCATTTTCCT CCCAGTTCTG GGGCTTTGGA AGGAGCTTGC GGATGAGGAG AG - #GGAGCCTC180- CGCAGGGCTC TGGCTCCCCT CCAGGGGCCG AGGCCGCACA CAAAGCCGCT CT - #GTGGCCCA240- ATTACACCTA CTGGATAGGA TTGTTGAGGG GACCTGAGAA ACTTGAGACG AC - #AAGAACGC300- GTAGCGCCTC GGCTGGCTGA GGGTGCTGAG CCCTCGTGTT GTGTTCTCTC CA - #GCTTTCCC360- CGTGCCTCAG CCACTCTTCA CGTTCCATCT GTGCTCTGTG CTGACCCGCC TG - #TGACTCAT420- ACTGGACATC AGTCCACCCT GAATACTGGA CTAAGCGCCA TGTGTGGGAG TG - #GCTCCAGT480- TCTGCTGCGA CCAGTACAAG TTGGACACCA ATTGCATCTC CTTCTGCAAC TT - #CAACATCA540- GTGGCCTGCA GCTGTGCAGC ATGACACAGG AGGAGTTCGT CGAGGCAGCT GG - #CCTCTGCG600- GCGAGTACCT GTACTTCATC CTCCAGAACA TCCGCACACA AGGTTACTCC TT - #TTTTAATG660- ACGCTGAAGA AAGCAAGGCC ACCATCAAAG ACTATGCTGA TTCCAACTGC TT - #GAAAACAA720- GTGGCATCAA AAGTCAAGAC TGTCACAGTC ATAGTAGAAC AAGCCTCCAA AG - #TTCTCATC780- TATGGGAATT TGTACGAGAC CTGCTTCTAT CTCCTGAAGA AAACTGTGGC AT - #TCTGGAAT840- GGGAAGATAG GGAACAAGGA ATTTTTCGGG TGGTTAAATC GGAAGCCCTG GC - #AAAGATGT900- GGGGACAAAG GAAGAAAAAT GACAGAATGA CGTATGAAAA GTTGAGCAGA GC - #CCTGAGAT960- ACTACTATAA AACAGGAATT TTGGAGCGGG TTGACCGAAG GTTAGTGTAC AA - #ATTTGGAA1020- AAAATGCACA CGGGTGGCAG GAAGACAAGC TATGATCTGC TCCAGGCATC AA - #GCTCATTT1080- TATGGATTTC TGTCTTTTAA AACAATCAGA TTGCAATAGA CATTCGAAAG GC - #TTCATTTT1140- CTTCTCTTTT TTTTTAACCT GCAAACATGC TGATAAAATT TCTCCACATC TC - #AGCTTACA1200- TTTGGATTCA GAGTTGTTGT CTACGGAGGG TGAGAGCAGA AACTCTTAAG AA - #ATCCTTTC1260- TTCTCCCTAA GGGGATGAGG GGATGATCTT TTGTGGTGTC TTGATCAAAC TT - #TATTTTCC1320- TAGAGTTGTG GAATGACAAC AGCCCATGCC ATTGATGCTG ATCAGAGAAA AA - #CTATTCAA1380- TTCTGCCATT AGAGACACAT CCAATGCTCC CATCCCAAAG GTTCAAAAGT TT - #TCAAATAA1440- CTGTGGCAGC TCACCAAAGG TGGGGGAAAG CATGATTAGT TTGCAGGTTA TG - #GTAGGAGA1500- GGGTGAGATA TAAGACATAC ATACTTTAGA TTTTAAATTA TTAAAGTCAA AA - #ATCCATAG1560- AAAAGTATCC CTTTTTTTTT TTTTTGAGAC GGGTTCTCAC TATGTTGCCC AG - #GGCTGGTC1620- TTGAACTCCT ATGCTCAAGT GATCCTCCCA CCTCGGCCTC CCAAAGTACT GT - #GATTACAA1680- GCGTGAGCCA CGGCACCTGG GCAGAAAAGT ATCTTAATTA ATGAAAGAGC TA - #AGCCATCA1740- AGCTGGGACT TAATTGGATT TAACATAGGT TCACAGAAAG TTTCCTAACC AG - #AGCATCTT1800- TTTGACCACT CAGCAAAACT TCCACAGACA TCCTTCTGGA CTTAAACACT TA - #ACATTAAC1860- CACATTATTA ATTGTTGCTG AGTTTATTCC CCCTTCTAAC TGATGGCTGG CA - #TCTGATAT1920- GCAGAGTTAG TCAACAGACA CTGGCATCAA TTACAAAATC ACTGCTGTTT CT - #GTGATTCA1980- AGCTGTCAAC ACAATAAAAT CGAAATTCAT TGATTCCATC TCTGGTCCCA GA - #TGTTAAAC2040- GTTTATAAAA CCGGAAATGT CCTAACAACT CTGTAATGGC AAATTAAATT GT - #GTGTCTTT2100- TTTGTTTTGT CTTTCTACCT GATGTGTATT CAAGCGCTAT AACACGTATT TC - #CTTGACAA2160- AAATAGTGAC AGTGAATTCA CACTAATAAA TGTTCATAGG TTAAAGTCTG CA - #CTGACATT2220- TTCTCATCAA TCACTGGTAT GTAAGTTATC AGTGACTGAC AGCTAGGTGG AC - #TGCCCCTA2280- GGACTTCTGT TTCACCAGAG CAGGAATCAA GTGGTGAGGC ACTGAATCGC TG - #TACAGGCT2340- GAAGACCTCC TTATTAGAGT TGAACTTCAA AGTAACTTGT TTTAAAAAAT GT - #GAATTACT2400- GTAAAATAAT CTATTTTGGA TTCATGTGTT TTCCAGGTGG ATATAGTTTG TA - #AACAATGT2460# 2498 ATGT TCAAAAAAAA AAAAAAAA- (2) INFORMATION FOR SEQ ID NO:11:- (i) SEQUENCE CHARACTERISTICS:#acids (A) LENGTH: 164 amino (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: protein- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:- Met Thr Gln Glu Glu Phe Val Glu Ala Ala Gl - #y Leu Cys Gly Glu Tyr# 15- Leu Tyr Phe Ile Leu Gln Asn Ile Arg Thr Gl - #n Gly Tyr Ser Phe Phe# 30- Asn Asp Ala Glu Glu Ser Lys Ala Thr Ile Ly - #s Asp Tyr Ala Asp Ser# 45- Asn Cys Leu Lys Thr Ser Gly Ile Lys Ser Gl - #n Asp Cys His Ser His# 60- Ser Arg Thr Ser Leu Gln Ser Ser His Leu Tr - #p Glu Phe Val Arg Asp#80- Leu Leu Leu Ser Pro Glu Glu Asn Cys Gly Il - #e Leu Glu Trp Glu Asp# 95- Arg Glu Gln Gly Ile Phe Arg Val Val Lys Se - #r Glu Ala Leu Ala Lys# 110- Met Trp Gly Gln Arg Lys Lys Asn Asp Arg Me - #t Thr Tyr Glu Lys Leu# 125- Ser Arg Ala Leu Arg Tyr Tyr Tyr Lys Thr Gl - #y Ile Leu Glu Arg Val# 140- Asp Arg Arg Leu Val Tyr Lys Phe Gly Lys As - #n Ala His Gly Trp Gln145 1 - #50 1 - #55 1 -#60- Glu Asp Lys Leu- (2) INFORMATION FOR SEQ ID NO:12:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Genomic DNA- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:# 21TAA T- (2) INFORMATION FOR SEQ ID NO:13:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13:# 21TAA T- (2) INFORMATION FOR SEQ ID NO:14:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 736 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Genomic DNA- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14:- AGGAAGTGAA GAACCTAGAT AATCCACCAA CCGGATAATC AGCTCTTGCA TA - #TTTGAGAG 60- TTGACTGCTT GACCTAAGCA TCTCCTCATA AGGTACCCTC CCTCCCAGGA CC - #TTCCCTTT120- CAAACCTCTC AAGGCTCTTA CCTGGGGCCA GGGGAGATAG GCTTTTCAAA GT - #CCATTGAA180- TTGCCAAGAG TCTCTGTCAA GAAGGCAGTC ATGGTGCCTG GAGAGGGAAC TT - #GCTGGGAG240- CCCCTTCAGA GCCTGGTACT TATAGAGCTA GGGAAAAGAT CTTGATGCCA AA - #GCAGGGTG300- GACTAAATAC AGACTAATAA ATGAGACAGG TGCTCAAGAG GGCCCCTCCA TA - #CCATCATC360- TCCTCCAGAT TTGGACTTCT ACTCACTTTG CTTTTACATT CCCTCTTCCC GA - #TGGTGTCT420- TTGGTGAGCA GGGTGCTTTT CACCTGAAAC AGCCTCTGAG CTGAAAAGAA CA - #GTCACCAC480- CAAATCAATT CCTCATCCAT TAACAGGTTG TCTCTCTGTT CTTGAGACAC AG - #GCATTACC540- TGGTTAGACC TGTTTTGTTT GAACACTAAC GTGTGAGTTG GCCAAATGCA AA - #TGAGCCAA600- TGTTTGTAAT CCTTTATTTT ATTTTTTTAA AGGGCTGGGT AGCCAATCAG AA - #GAGGGGGA660- AGTGACTTAG GGAATTCCCG GTTGGTGGCT TATTGCTTAA CATCCTACAA AA - #TGATTTAA720# 736- (2) INFORMATION FOR SEQ ID NO:15:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 333 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Genomic DNA- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:- GCCAGAGTCC TCCTTGAGAA CTTACAATGT GTCCATATTA AGGATCTGCT GT - #GTTTGATG 60- ATTTTGTGAT TACACTTTAA ACTTCTTATC CATAAAGGAC ATACTTGATA TA - #TCTGAGAC120- TTGTAGTAGA AGGCCTTGAG ACATCCATCT CATCCCATCA TTATCTATCT AT - #CATCTATC180- TATCTATCTA TCTATCTATC TATCTATCTA TCTATCATCT ATCTATCTAT CG - #CCAGTACT240- GTCTTGTTGA AGTTGGCAGT AGGGTGAAAG ACCTCAAACT CCAAAGGACT TT - #CCGTATGG300# 333 ATTC TAGCTTTTCT GTG- (2) INFORMATION FOR SEQ ID NO:16:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16:# 21AAG T- (2) INFORMATION FOR SEQ ID NO:17:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17:# 21ACC C- (2) INFORMATION FOR SEQ ID NO:18:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18:# 21GCA G- (2) INFORMATION FOR SEQ ID NO:19:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19:# 21GTG C- (2) INFORMATION FOR SEQ ID NO:20:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20:# 21AGG G- (2) INFORMATION FOR SEQ ID NO:21:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21:# 21ACA C- (2) INFORMATION FOR SEQ ID NO:22:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22:# 23 GGCC TGT- (2) INFORMATION FOR SEQ ID NO:23:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23:# 21CCA A- (2) INFORMATION FOR SEQ ID NO:24:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24:# 21AGG G- (2) INFORMATION FOR SEQ ID NO:25:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25:# 21GGT G- (2) INFORMATION FOR SEQ ID NO:26:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26:# 21GTG C- (2) INFORMATION FOR SEQ ID NO:27:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27:# 21CAG C- (2) INFORMATION FOR SEQ ID NO:28:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28:# 22GGAC TT- (2) INFORMATION FOR SEQ ID NO:29:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29:# 21GAA A- (2) INFORMATION FOR SEQ ID NO:30:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30:# 21AGC T- (2) INFORMATION FOR SEQ ID NO:31:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31:# 21ATG A- (2) INFORMATION FOR SEQ ID NO:32:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32:# 21GAC G- (2) INFORMATION FOR SEQ ID NO:33:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33:# 22GCTG AC- (2) INFORMATION FOR SEQ ID NO:34:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34:# 21CAT T- (2) INFORMATION FOR SEQ ID NO:35:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35:# 21GCC T- (2) INFORMATION FOR SEQ ID NO:36:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36:# 21CGT G- (2) INFORMATION FOR SEQ ID NO:37:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37:# 21CTA C- (2) INFORMATION FOR SEQ ID NO:38:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38:# 21TTT A- (2) INFORMATION FOR SEQ ID NO:39:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39:# 21CTC C- (2) INFORMATION FOR SEQ ID NO:40:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40:# 21CCA G- (2) INFORMATION FOR SEQ ID NO:41:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41:# 21TAA T- (2) INFORMATION FOR SEQ ID NO:42:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42:# 21CAT T- (2) INFORMATION FOR SEQ ID NO:43:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:43:# 21CAG C- (2) INFORMATION FOR SEQ ID NO:44:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44:# 21TAC C- (2) INFORMATION FOR SEQ ID NO:45:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45:# 21TTA T- (2) INFORMATION FOR SEQ ID NO:46:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46:# 21TCC C- (2) INFORMATION FOR SEQ ID NO:47:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47:# 21AAG A- (2) INFORMATION FOR SEQ ID NO:48:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48:# 21TGG C- (2) INFORMATION FOR SEQ ID NO:49:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49:# 21TGG C- (2) INFORMATION FOR SEQ ID NO:50:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:50:# 21ATA C- (2) INFORMATION FOR SEQ ID NO:51:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51:# 21GCT G- (2) INFORMATION FOR SEQ ID NO:52:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52:# 21TAA G- (2) INFORMATION FOR SEQ ID NO:53:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53:# 23 ACTT GAG- (2) INFORMATION FOR SEQ ID NO:54:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:54:# 21GAG A- (2) INFORMATION FOR SEQ ID NO:55:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:55:# 21CCT G- (2) INFORMATION FOR SEQ ID NO:56:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:56:# 21GT G- (2) INFORMATION FOR SEQ ID NO:57:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:57:# 21GGA G- (2) INFORMATION FOR SEQ ID NO:58:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:58:# 21CCT T- (2) INFORMATION FOR SEQ ID NO:59:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:59:# 21ACC A- (2) INFORMATION FOR SEQ ID NO:60:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:60:# 21AAA C- (2) INFORMATION FOR SEQ ID NO:61:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:61:# 21CCC A- (2) INFORMATION FOR SEQ ID NO:62:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:62:# 21CTA G- (2) INFORMATION FOR SEQ ID NO:63:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:63:# 21ATG A- (2) INFORMATION FOR SEQ ID NO:64:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:64:# 21ATC C- (2) INFORMATION FOR SEQ ID NO:65:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:65:# 21TCC T- (2) INFORMATION FOR SEQ ID NO:66:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:66:# 21CTC C- (2) INFORMATION FOR SEQ ID NO:67:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:67:# 21TGT A- (2) INFORMATION FOR SEQ ID NO:68:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:68:# 21TCA T- (2) INFORMATION FOR SEQ ID NO:69:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:69:# 21ATG T- (2) INFORMATION FOR SEQ ID NO:70:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:70:# 21ACT T- (2) INFORMATION FOR SEQ ID NO:71:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71:# 21AAT T- (2) INFORMATION FOR SEQ ID NO:72:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:72:# 21GCA C- (2) INFORMATION FOR SEQ ID NO:73:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:73:# 21CCT C- (2) INFORMATION FOR SEQ ID NO:74:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74:# 21TCA T- (2) INFORMATION FOR SEQ ID NO:75:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:75:# 21AAC A- (2) INFORMATION FOR SEQ ID NO:76:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76:# 21CTT T- (2) INFORMATION FOR SEQ ID NO:77:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:77:# 21TGG C- (2) INFORMATION FOR SEQ ID NO:78:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:78:# 21TTT G- (2) INFORMATION FOR SEQ ID NO:79:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:79:# 21TAT A- (2) INFORMATION FOR SEQ ID NO:80:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:80:# 21ACT G- (2) INFORMATION FOR SEQ ID NO:81:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 31 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:81:# 31 NNNN NACACTGCCT G- (2) INFORMATION FOR SEQ ID NO:82:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:82:# 21CTT A- (2) INFORMATION FOR SEQ ID NO:83:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:83:# 21CTG T- (2) INFORMATION FOR SEQ ID NO:84:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:84:# 21ATA T- (2) INFORMATION FOR SEQ ID NO:85:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:85:# 21AGG C- (2) INFORMATION FOR SEQ ID NO:86:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:86:# 21GAA T- (2) INFORMATION FOR SEQ ID NO:87:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:87:# 21TGG T- (2) INFORMATION FOR SEQ ID NO:88:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:88:# 21TTT C- (2) INFORMATION FOR SEQ ID NO:89:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:89:# 21TTT T- (2) INFORMATION FOR SEQ ID NO:90:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:90:# 21TAC T- (2) INFORMATION FOR SEQ ID NO:91:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:91:# 21GTG G- (2) INFORMATION FOR SEQ ID NO:92:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:92:# 21CCT G- (2) INFORMATION FOR SEQ ID NO:93:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:93:# 21ATT T- (2) INFORMATION FOR SEQ ID NO:94:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:94:# 21ACA C- (2) INFORMATION FOR SEQ ID NO:95:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:95:# 21GCC T- (2) INFORMATION FOR SEQ ID NO:96:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:96:# 21TCC C- (2) INFORMATION FOR SEQ ID NO:97:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:97:# 21AGA T- (2) INFORMATION FOR SEQ ID NO:98:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:98:# 22CCCG CC- (2) INFORMATION FOR SEQ ID NO:99:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:99:# 22CAAC CC- (2) INFORMATION FOR SEQ ID NO:100:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:100:# 21AAT A- (2) INFORMATION FOR SEQ ID NO:101:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:101:# 21GCA G- (2) INFORMATION FOR SEQ ID NO:102:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:102:# 21TGT G- (2) INFORMATION FOR SEQ ID NO:103:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:103:# 27 ATGT GCGCGTG- (2) INFORMATION FOR SEQ ID NO:104:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:104:# 21CCA A- (2) INFORMATION FOR SEQ ID NO:105:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:105:# 21TAC G- (2) INFORMATION FOR SEQ ID NO:106:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:106:# 21GGA C- (2) INFORMATION FOR SEQ ID NO:107:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:107:# 21ATG T- (2) INFORMATION FOR SEQ ID NO:108:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:108:# 21ATG A- (2) INFORMATION FOR SEQ ID NO:109:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:109:# 21CAC A- (2) INFORMATION FOR SEQ ID NO:110:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:110:# 21GTC A- (2) INFORMATION FOR SEQ ID NO:111:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:111:# 23 TAGT CTG- (2) INFORMATION FOR SEQ ID NO:112:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:112:# 21GCC A- (2) INFORMATION FOR SEQ ID NO:113:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:113:# 21GCT G- (2) INFORMATION FOR SEQ ID NO:114:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:114:# 21TTA G- (2) INFORMATION FOR SEQ ID NO:115:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:115:# 21TTG A- (2) INFORMATION FOR SEQ ID NO:116:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:116:# 21TGT A- (2) INFORMATION FOR SEQ ID NO:117:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:117:# 21GCC T- (2) INFORMATION FOR SEQ ID NO:118:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:118:# 21CTA C- (2) INFORMATION FOR SEQ ID NO:119:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:119:# 21CCA G- (2) INFORMATION FOR SEQ ID NO:120:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:120:# 21ACA A- (2) INFORMATION FOR SEQ ID NO:121:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:121:# 21GCA G- (2) INFORMATION FOR SEQ ID NO:122:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:122:# 21TTC C- (2) INFORMATION FOR SEQ ID NO:123:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:123:# 21TTC C- (2) INFORMATION FOR SEQ ID NO:124:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:124:# 21AAA G- (2) INFORMATION FOR SEQ ID NO:125:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:125:# 21CCC A- (2) INFORMATION FOR SEQ ID NO:126:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:126:# 21CAG G- (2) INFORMATION FOR SEQ ID NO:127:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:127:# 21CAT T- (2) INFORMATION FOR SEQ ID NO:128:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:128:# 21TCC C- (2) INFORMATION FOR SEQ ID NO:129:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:129:# 21AAG C- (2) INFORMATION FOR SEQ ID NO:130:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:130:# 21GGG C- (2) INFORMATION FOR SEQ ID NO:131:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:131:# 21GTG G- (2) INFORMATION FOR SEQ ID NO:132:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:132:# 25 AAAT AAGAC- (2) INFORMATION FOR SEQ ID NO:133:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:133:# 21AAA C- (2) INFORMATION FOR SEQ ID NO:134:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:134:# 21ATT C- (2) INFORMATION FOR SEQ ID NO:135:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:135:# 21ACT G- (2) INFORMATION FOR SEQ ID NO:136:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:136:# 21CCC T- (2) INFORMATION FOR SEQ ID NO:137:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:137:# 21AGA T- (2) INFORMATION FOR SEQ ID NO:138:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:138:# 21CTG T- (2) INFORMATION FOR SEQ ID NO:139:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:139:# 21TTG T- (2) INFORMATION FOR SEQ ID NO:140:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:140:# 21ACA T- (2) INFORMATION FOR SEQ ID NO:141:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:141:# 21CTC C- (2) INFORMATION FOR SEQ ID NO:142:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:142:# 21CAC T- (2) INFORMATION FOR SEQ ID NO:143:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:143:# 21TCC T- (2) INFORMATION FOR SEQ ID NO:144:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:144:# 21AAT T- (2) INFORMATION FOR SEQ ID NO:145:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:145:# 21TTA A- (2) INFORMATION FOR SEQ ID NO:146:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:146:# 21TCA C- (2) INFORMATION FOR SEQ ID NO:147:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:147:# 21GCT C- (2) INFORMATION FOR SEQ ID NO:148:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:148:# 21CTT C- (2) INFORMATION FOR SEQ ID NO:149:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:149:# 21TAA G- (2) INFORMATION FOR SEQ ID NO:150:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:150:# 21CAA A- (2) INFORMATION FOR SEQ ID NO:151:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:151:# 21GTA T- (2) INFORMATION FOR SEQ ID NO:152:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:152:# 21CTC C- (2) INFORMATION FOR SEQ ID NO:153:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:153:# 21AAA C- (2) INFORMATION FOR SEQ ID NO:154:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:154:# 21AAA G- (2) INFORMATION FOR SEQ ID NO:155:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:155:# 21TCA G- (2) INFORMATION FOR SEQ ID NO:156:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:156:# 22TCAC CT- (2) INFORMATION FOR SEQ ID NO:157:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:157:# 21AGA A- (2) INFORMATION FOR SEQ ID NO:158:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:158:# 21CCT T- (2) INFORMATION FOR SEQ ID NO:159:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:159:# 22TTTT TT- (2) INFORMATION FOR SEQ ID NO:160:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 18 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:160:# 18 GG- (2) INFORMATION FOR SEQ ID NO:161:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:161:# 24 TAAC TTGG- (2) INFORMATION FOR SEQ ID NO:162:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:162:# 22TTTC AG- (2) INFORMATION FOR SEQ ID NO:163:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 31 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:163:# 31 TGCT ATCACATCAC C- (2) INFORMATION FOR SEQ ID NO:164:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:164:# 24 AAGT AAAC- (2) INFORMATION FOR SEQ ID NO:165:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 29 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:165:# 29 CTAA GATGGCTGG- (2) INFORMATION FOR SEQ ID NO:166:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:166:# 23 AGAC AAG- (2) INFORMATION FOR SEQ ID NO:167:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 29 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:167:# 29 GTCA GGAGGTAGG- (2) INFORMATION FOR SEQ ID NO:168:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:168:# 23 GTAC ATG- (2) INFORMATION FOR SEQ ID NO:169:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 30 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:169:# 30 CACA AACATCTCTG- (2) INFORMATION FOR SEQ ID NO:170:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:170:# 22GTTT GG- (2) INFORMATION FOR SEQ ID NO:171:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 29 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:171:# 29 ACAC GGTGAAATC- (2) INFORMATION FOR SEQ ID NO:172:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:172:# 27 TCCC AAAATTC- (2) INFORMATION FOR SEQ ID NO:173:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:173:#20 CGAA- (2) INFORMATION FOR SEQ ID NO:174:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:174:# 22AACG TG- (2) INFORMATION FOR SEQ ID NO:175:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 30 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:175:# 30 AGGA AAGAAACCAC- (2) INFORMATION FOR SEQ ID NO:176:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:176:# 25 TCTG TGCTG- (2) INFORMATION FOR SEQ ID NO:177:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 31 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:177:# 31 AGAT CCTTGACCCA G- (2) INFORMATION FOR SEQ ID NO:178:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:178:# 22TGCA TC- (2) INFORMATION FOR SEQ ID NO:179:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 30 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:179:# 30 CTTA CTCTTGCCCC- (2) INFORMATION FOR SEQ ID NO:180:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:180:# 24 GCTG AGAC- (2) INFORMATION FOR SEQ ID NO:181:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 32 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:181:# 32 ACCT TACATTGTTG AG- (2) INFORMATION FOR SEQ ID NO:182:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:182:#20 CCTT- (2) INFORMATION FOR SEQ ID NO:183:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 30 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:183:# 30 GAGT TTCTGTTGGG- (2) INFORMATION FOR SEQ ID NO:184:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:184:#20 TTGC- (2) INFORMATION FOR SEQ ID NO:185:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 28 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:185:# 28 AAGC TAGAGTGG- (2) INFORMATION FOR SEQ ID NO:186:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:186:# 24 ATTT AACC- (2) INFORMATION FOR SEQ ID NO:187:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 28 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:187:# 28 CAGA GCCACTCA- (2) INFORMATION FOR SEQ ID NO:188:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:188:#20 TACT- (2) INFORMATION FOR SEQ ID NO:189:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 30 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:189:# 30 TTGA GCTTTCTACC- (2) INFORMATION FOR SEQ ID NO:190:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:190:#20 CCAG- (2) INFORMATION FOR SEQ ID NO:191:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 31 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:191:# 31 CCTT ACACAAGCAC A- (2) INFORMATION FOR SEQ ID NO:192:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:192:#20 AGTT- (2) INFORMATION FOR SEQ ID NO:193:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:193:# 27 AATG AGCTGTG- (2) INFORMATION FOR SEQ ID NO:194:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:194:# 22AATG TC- (2) INFORMATION FOR SEQ ID NO:195:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 30 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:195:# 30 ATCA CATGACCTTG- (2) INFORMATION FOR SEQ ID NO:196:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:196:# 21GTT C- (2) INFORMATION FOR SEQ ID NO:197:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 28 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:197:# 28 TGTT CAGAAAGG- (2) INFORMATION FOR SEQ ID NO:198:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:198:# 22CGCA TC- (2) INFORMATION FOR SEQ ID NO:199:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 31 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:199:# 31 ATGC TAGGTCTGTA G- (2) INFORMATION FOR SEQ ID NO:200:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:200:# 22GGAC AC- (2) INFORMATION FOR SEQ ID NO:201:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 28 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:201:# 28 AGAC ATACAAAC- (2) INFORMATION FOR SEQ ID NO:202:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:202:# 22AGCG AC- (2) INFORMATION FOR SEQ ID NO:203:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 29 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:203:# 29 GTAG GGTGTCACC- (2) INFORMATION FOR SEQ ID NO:204:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:204:# 24 AGGT TTTG- (2) INFORMATION FOR SEQ ID NO:205:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 31 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:205:# 31 ACTG GTGTAGGAGT C- (2) INFORMATION FOR SEQ ID NO:206:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:206:#20 TCTC- (2) INFORMATION FOR SEQ ID NO:207:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:207:#20 CATG- (2) INFORMATION FOR SEQ ID NO:208:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:208:# 23 AAAG GTG- (2) INFORMATION FOR SEQ ID NO:209:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:209:# 25 TGCT GCATC- (2) INFORMATION FOR SEQ ID NO:210:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:210:#20 GCAG- (2) INFORMATION FOR SEQ ID NO:211:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #211:# 26 CAAC AAACCC- (2) INFORMATION FOR SEQ ID NO:212:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:212:# 21TTC C- (2) INFORMATION FOR SEQ ID NO:213:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 32 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:213:# 32 ACGA TCTGTAGTGG TG- (2) INFORMATION FOR SEQ ID NO:214:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:214:# 25 TAGC CACGG- (2) INFORMATION FOR SEQ ID NO:215:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:215:#20 GTGG- (2) INFORMATION FOR SEQ ID NO:216:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 19 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:216:#19 AGC- (2) INFORMATION FOR SEQ ID NO:217:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:217:# 21CCT G- (2) INFORMATION FOR SEQ ID NO:218:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 17 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:218:# 17 C- (2) INFORMATION FOR SEQ ID NO:219:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 28 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:219:# 28 TGTG TATGGATG- (2) INFORMATION FOR SEQ ID NO:220:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:220:#20 GGTG- (2) INFORMATION FOR SEQ ID NO:221:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:221:#20 ATGG- (2) INFORMATION FOR SEQ ID NO:222:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 19 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:222:#19 AGG- (2) INFORMATION FOR SEQ ID NO:223:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:223:# 27 GAGA TGTTACT- (2) INFORMATION FOR SEQ ID NO:224:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:224:# 25 GTAA TTTGG- (2) INFORMATION FOR SEQ ID NO:225:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 32 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:225:# 32 CAAT TCCATCATAA CA- (2) INFORMATION FOR SEQ ID NO:226:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:226:#20 GCGG- (2) INFORMATION FOR SEQ ID NO:227:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:227:#20 ATGG- (2) INFORMATION FOR SEQ ID NO:228:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:228:#20 CGTG- (2) INFORMATION FOR SEQ ID NO:229:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:229:#20 TTTT- (2) INFORMATION FOR SEQ ID NO:230:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:230:#20 TGAG- (2) INFORMATION FOR SEQ ID NO:231:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:231:# 26 GGGG AAGGTG- (2) INFORMATION FOR SEQ ID NO:232:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 19 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:232:#19 TCC- (2) INFORMATION FOR SEQ ID NO:233:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:233:# 25 GGAT TGTAG- (2) INFORMATION FOR SEQ ID NO:234:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:234:#20 GTTC- (2) INFORMATION FOR SEQ ID NO:235:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:235:# 26 GTGA GACTCA- (2) INFORMATION FOR SEQ ID NO:236:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:236:#20 GGAG- (2) INFORMATION FOR SEQ ID NO:237:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:237:# 27 GCAA GCAATCA- (2) INFORMATION FOR SEQ ID NO:238:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 18 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:238:# 18 CA- (2) INFORMATION FOR SEQ ID NO:239:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:239:# 27 TGAT GCAAAGT- (2) INFORMATION FOR SEQ ID NO:240:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:240:#20 TTCG- (2) INFORMATION FOR SEQ ID NO:241:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:241:# 26 AGGG AGCAGC- (2) INFORMATION FOR SEQ ID NO:242:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:242:#20 TCAT- (2) INFORMATION FOR SEQ ID NO:243:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:243:# 27 CTGC CAACTTC- (2) INFORMATION FOR SEQ ID NO:244:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:244:#20 CATA- (2) INFORMATION FOR SEQ ID NO:245:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 27 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:245:# 27 AATT GGTAGGA- (2) INFORMATION FOR SEQ ID NO:246:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:246:# 22AGGT GC- (2) INFORMATION FOR SEQ ID NO:247:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 30 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:247:# 30 TTCA GTTTAGGAAC- (2) INFORMATION FOR SEQ ID NO:248:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:248:# 24 TCTT CCTC- (2) INFORMATION FOR SEQ ID NO:249:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 30 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:249:# 30 AAGG CATCGTAGAG- (2) INFORMATION FOR SEQ ID NO:250:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:250:# 21GGG G- (2) INFORMATION FOR SEQ ID NO:251:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO: - #251:# 22GTTG GC- (2) INFORMATION FOR SEQ ID NO:252:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:252:#20 CATG- (2) INFORMATION FOR SEQ ID NO:253:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:253:# 25 AAAT AAAGT- (2) INFORMATION FOR SEQ ID NO:254:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:254:# 23 ATAT ACC- (2) INFORMATION FOR SEQ ID NO:255:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:255:#20 TTTG- (2) INFORMATION FOR SEQ ID NO:256:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 19 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:256:#19 AAT- (2) INFORMATION FOR SEQ ID NO:257:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:257:#20 CCTG- (2) INFORMATION FOR SEQ ID NO:258:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:258:#20 GAAT- (2) INFORMATION FOR SEQ ID NO:259:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:259:#20 TCTC- (2) INFORMATION FOR SEQ ID NO:260:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:260:#20 GCAT- (2) INFORMATION FOR SEQ ID NO:261:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:261:#20 CGAA- (2) INFORMATION FOR SEQ ID NO:262:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:262:# 24 CTGC ACTC- (2) INFORMATION FOR SEQ ID NO:263:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 29 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:263:# 29 TATC CCTCAAATG- (2) INFORMATION FOR SEQ ID NO:264:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:264:# 22TTAA AG- (2) INFORMATION FOR SEQ ID NO:265:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:265:# 24 AAGG CTAC- (2) INFORMATION FOR SEQ ID NO:266:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:266:# 23 TTTG GAG- (2) INFORMATION FOR SEQ ID NO:267:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 24 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:267:# 24 GAAT TAGG- (2) INFORMATION FOR SEQ ID NO:268:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:268:#20 ACTC- (2) INFORMATION FOR SEQ ID NO:269:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 29 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:269:# 29 GGGC TTTTAAACC- (2) INFORMATION FOR SEQ ID NO:270:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:270:#20 ATGG- (2) INFORMATION FOR SEQ ID NO:271:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:271:#20 CTTT- (2) INFORMATION FOR SEQ ID NO:272:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 19 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:272:#19 GTG- (2) INFORMATION FOR SEQ ID NO:273:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 26 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:273:# 26 CCTC CTCTGC- (2) INFORMATION FOR SEQ ID NO:274:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 10 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:274:# 10- (2) INFORMATION FOR SEQ ID NO:275:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 10 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:275:# 10- (2) INFORMATION FOR SEQ ID NO:276:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 18 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:276:# 18 GT- (2) INFORMATION FOR SEQ ID NO:277:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 10 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:277:# 10- (2) INFORMATION FOR SEQ ID NO:278:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 10 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:278:# 10- (2) INFORMATION FOR SEQ ID NO:279:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 10 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:279:# 10- (2) INFORMATION FOR SEQ ID NO:280:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 10 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:280:# 10- (2) INFORMATION FOR SEQ ID NO:281:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 14 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:281:# 14- (2) INFORMATION FOR SEQ ID NO:282:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:282:# 22TATA TA- (2) INFORMATION FOR SEQ ID NO:283:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:283:# 22AAAA TC- (2) INFORMATION FOR SEQ ID NO:284:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 38 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:284:# 38 TGGT GTGGTATGTG TACATATG- (2) INFORMATION FOR SEQ ID NO:285:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:285:# 22TGAT AA- (2) INFORMATION FOR SEQ ID NO:286:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 86 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:286:- AGACAGTCTC AAAAAATATT TTAAAGAAAA AGCTGGATAA ATAACTAGCT TT - #AAGAAAAT 60# 86 AAGA AAGTAA- (2) INFORMATION FOR SEQ ID NO:287:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 86 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:287:- AACTAGCTTT AAGAAAATAA GAAGAAAAAG AAAGAAGAAA GTAAGAAAGA GA - #AAGAAAAG 60# 86 AATG ATTGAC- (2) INFORMATION FOR SEQ ID NO:288:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:288:# 22TTCT CT- (2) INFORMATION FOR SEQ ID NO:289:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 22 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:289:# 22GAGT GG- (2) INFORMATION FOR SEQ ID NO:290:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 42 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:290:# 42 GTGT GCATGAGTGC ACATTCTACA TA- (2) INFORMATION FOR SEQ ID NO:291:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 25 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:291:# 25 CAAG TTGGC- (2) INFORMATION FOR SEQ ID NO:292:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 45 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:292:# 45AGG CAAGCGCACC ATACATCCAA GAAAA- (2) INFORMATION FOR SEQ ID NO:293:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:293:#20 TGCC- (2) INFORMATION FOR SEQ ID NO:294:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:294:#20 GCAG- (2) INFORMATION FOR SEQ ID NO:295:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:295:#20 GCCT- (2) INFORMATION FOR SEQ ID NO:296:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:296:#20 GTTG- (2) INFORMATION FOR SEQ ID NO:297:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 19 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:297:#19 ACA- (2) INFORMATION FOR SEQ ID NO:298:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:298:#20 CTGA- (2) INFORMATION FOR SEQ ID NO:299:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:299:#20 TTCA- (2) INFORMATION FOR SEQ ID NO:300:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:300:#20 TACA- (2) INFORMATION FOR SEQ ID NO:301:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:301:#20 AGTA- (2) INFORMATION FOR SEQ ID NO:302:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:302:#20 GTGT- (2) INFORMATION FOR SEQ ID NO:303:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:303:#20 TGGT- (2) INFORMATION FOR SEQ ID NO:304:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:304:#20 ACTC- (2) INFORMATION FOR SEQ ID NO:305:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:305:#20 GTTC- (2) INFORMATION FOR SEQ ID NO:306:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:306:#20 CCTT- (2) INFORMATION FOR SEQ ID NO:307:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:307:#20 AACC- (2) INFORMATION FOR SEQ ID NO:308:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:308:#20 ATTC- (2) INFORMATION FOR SEQ ID NO:309:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:309:#20 GCAG- (2) INFORMATION FOR SEQ ID NO:310:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:310:#20 AAAG- (2) INFORMATION FOR SEQ ID NO:311:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:311:#20 TAAT- (2) INFORMATION FOR SEQ ID NO:312:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:312:#20 CTAT- (2) INFORMATION FOR SEQ ID NO:313:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:313:#20 CTGT- (2) INFORMATION FOR SEQ ID NO:314:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:314:#20 CTTC- (2) INFORMATION FOR SEQ ID NO:315:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:315:#20 CCTG- (2) INFORMATION FOR SEQ ID NO:316:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:316:#20 CTCT- (2) INFORMATION FOR SEQ ID NO:317:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:317:#20 TTAA- (2) INFORMATION FOR SEQ ID NO:318:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:318:#20 ACCC- (2) INFORMATION FOR SEQ ID NO:319:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:319:#20 AAAG- (2) INFORMATION FOR SEQ ID NO:320:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:320:#20 ATTC- (2) INFORMATION FOR SEQ ID NO:321:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:321:#20 GGGC- (2) INFORMATION FOR SEQ ID NO:322:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:322:#20 GTGG- (2) INFORMATION FOR SEQ ID NO:323:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:323:#20 CTCT- (2) INFORMATION FOR SEQ ID NO:324:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:324:#20 GCAG- (2) INFORMATION FOR SEQ ID NO:325:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:325:#20 AGTA- (2) INFORMATION FOR SEQ ID NO:326:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:326:#20 CCAT- (2) INFORMATION FOR SEQ ID NO:327:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:327:#20 AACT- (2) INFORMATION FOR SEQ ID NO:328:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:328:#20 TGGA- (2) INFORMATION FOR SEQ ID NO:329:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:329:#20 TGTC- (2) INFORMATION FOR SEQ ID NO:330:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:330:#20 CACC- (2) INFORMATION FOR SEQ ID NO:331:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:331:#20 TGGC- (2) INFORMATION FOR SEQ ID NO:332:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:332:#20 GAGG- (2) INFORMATION FOR SEQ ID NO:333:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:333:#20 AGTT- (2) INFORMATION FOR SEQ ID NO:334:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:334:#20 CTAC- (2) INFORMATION FOR SEQ ID NO:335:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 20 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:335:#20 TTTC- (2) INFORMATION FOR SEQ ID NO:336:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 23 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:336:# 23 CATC AGG- (2) INFORMATION FOR SEQ ID NO:337:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 21 base (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: Other- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:337:# 21TTC T- (2) INFORMATION FOR SEQ ID NO:338:- (i) SEQUENCE CHARACTERISTICS:#pairs (A) LENGTH: 848 base (B) TYPE: nucleic acid (C) STRANDEDNESS: double (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: cDNA- (ix) FEATURE: (A) NAME/KEY: Coding Se - #quence (B) LOCATION: 1...848 (D) OTHER INFORMATION:- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:338:- ATG ATT CTG GAA GGA AGT GGT GTA ATG AAT CT - #C AAC CCA GCC AAC AAC 48Met Ile Leu Glu Gly Ser Gly Val Met Asn Le - #u Asn Pro Ala Asn Asn# 15- CTC CTT CAC CAG CAA CCA GCC TGG CCG GAC AG - #C TAC CCC ACA TGC AAT 96Leu Leu His Gln Gln Pro Ala Trp Pro Asp Se - #r Tyr Pro Thr Cys Asn# 30- GTT TCC AGC GGT TTT TTT GGA AGC CAG TGG CA - #T GAA ATC CAC CCT CAG144Val Ser Ser Gly Phe Phe Gly Ser Gln Trp Hi - #s Glu Ile His Pro Gln# 45- TAC TGG ACC AAA TAC CAG GTG TGG GAA TGG CT - #G CAG CAC CTC CTG GAC192Tyr Trp Thr Lys Tyr Gln Val Trp Glu Trp Le - #u Gln His Leu Leu Asp# 60- ACC AAC CAG CTA GAC GCT AGC TGC ATC CCT TT - #C CAG GAG TTC GAC ATT240Thr Asn Gln Leu Asp Ala Ser Cys Ile Pro Ph - #e Gln Glu Phe Asp Ile#80- AGC GGA GAA CAC CTG TGC AGC ATG AGT CTG CA - #G GAG TTC ACG AGG GCA288Ser Gly Glu His Leu Cys Ser Met Ser Leu Gl - #n Glu Phe Thr Arg Ala# 95- GCA GGC TCA GCT GGG CAG CTG CTC TAC AGC AA - #C CTA CAG CAT CTC AAG336Ala Gly Ser Ala Gly Gln Leu Leu Tyr Ser As - #n Leu Gln His Leu Lys# 110- TGG AAC GGC CAA TGC AGC AGT GAC CTT TTC CA - #G TCC GCA CAC AAT GTC384Trp Asn Gly Gln Cys Ser Ser Asp Leu Phe Gl - #n Ser Ala His Asn Val# 125- ATT GTC AAG ACT GAA CAA ACC GAT CCT TCC AT - #C ATG AAC ACA TGG AAA432Ile Val Lys Thr Glu Gln Thr Asp Pro Ser Il - #e Met Asn Thr Trp Lys# 140- GAA GAA AAC TAT CTC TAT GAT CCC AGC TAT GG - #T AGC ACA GTA GAT CTG480Glu Glu Asn Tyr Leu Tyr Asp Pro Ser Tyr Gl - #y Ser Thr Val Asp Leu145 1 - #50 1 - #55 1 -#60- TTG GAC AGT AAG ACT TTC TGC CGG GCT CAG AT - #C TCC ATG ACA ACC TCC528Leu Asp Ser Lys Thr Phe Cys Arg Ala Gln Il - #e Ser Met Thr Thr Ser# 175- AGT CAC CTT CCA GTT GCA GAG TCA CCT GAT AT - #G AAA AAG GAG CAA GAC576Ser His Leu Pro Val Ala Glu Ser Pro Asp Me - #t Lys Lys Glu Gln Asp# 190- CAC CCT GTA AAG TCC CAC ACC AAA AAG CAC AA - #C CCA AGA GGC ACT CAC624His Pro Val Lys Ser His Thr Lys Lys His As - #n Pro Arg Gly Thr His# 205- TTA TGG GAG TTC ATC CGA GAC ATT CTC TTG AG - #C CCA GAC AAG AAC CCA672Leu Trp Glu Phe Ile Arg Asp Ile Leu Leu Se - #r Pro Asp Lys Asn Pro# 220- GGG CTG ATC AAA TGG GAA GAC CGT TCG GAA GG - #C ATC TTC AGG TTC CTG720Gly Leu Ile Lys Trp Glu Asp Arg Ser Glu Gl - #y Ile Phe Arg Phe Leu225 2 - #30 2 - #35 2 -#40- AAG TCA GAA GCT GTG GCT CAG CTG TGG GGG AA - #A AAG AAA AAT AAC AGT768Lys Ser Glu Ala Val Ala Gln Leu Trp Gly Ly - #s Lys Lys Asn Asn Ser# 255- AGC ATG ACA TAC GAG AAG CTC AGC CGG GCT AT - #G AGA TAT TAC TAC AAA816Ser Met Thr Tyr Glu Lys Leu Ser Arg Ala Me - #t Arg Tyr Tyr Tyr Lys# 270# 848C CTG GAA CGT GTG GAT GGA CGA CG - #Arg Glu Ile Leu Glu Arg Val Asp Gly Arg Ar - #g# 280- (2) INFORMATION FOR SEQ ID NO:339:- (i) SEQUENCE CHARACTERISTICS:#acids (A) LENGTH: 283 amino (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear- (ii) MOLECULE TYPE: protein- (v) FRAGMENT TYPE: internal- (xi) SEQUENCE DESCRIPTION: SEQ ID NO:339:- Met Ile Leu Glu Gly Ser Gly Val Met Asn Le - #u Asn Pro Ala Asn Asn# 15- Leu Leu His Gln Gln Pro Ala Trp Pro Asp Se - #r Tyr Pro Thr Cys Asn# 30- Val Ser Ser Gly Phe Phe Gly Ser Gln Trp Hi - #s Glu Ile His Pro Gln# 45- Tyr Trp Thr Lys Tyr Gln Val Trp Glu Trp Le - #u Gln His Leu Leu Asp# 60- Thr Asn Gln Leu Asp Ala Ser Cys Ile Pro Ph - #e Gln Glu Phe Asp Ile#80- Ser Gly Glu His Leu Cys Ser Met Ser Leu Gl - #n Glu Phe Thr Arg Ala# 95- Ala Gly Ser Ala Gly Gln Leu Leu Tyr Ser As - #n Leu Gln His Leu Lys# 110- Trp Asn Gly Gln Cys Ser Ser Asp Leu Phe Gl - #n Ser Ala His Asn Val# 125- Ile Val Lys Thr Glu Gln Thr Asp Pro Ser Il - #e Met Asn Thr Trp Lys# 140- Glu Glu Asn Tyr Leu Tyr Asp Pro Ser Tyr Gl - #y Ser Thr Val Asp Leu145 1 - #50 1 - #55 1 -#60- Leu Asp Ser Lys Thr Phe Cys Arg Ala Gln Il - #e Ser Met Thr Thr Ser# 175- Ser His Leu Pro Val Ala Glu Ser Pro Asp Me - #t Lys Lys Glu Gln Asp# 190- His Pro Val Lys Ser His Thr Lys Lys His As - #n Pro Arg Gly Thr His# 205- Leu Trp Glu Phe Ile Arg Asp Ile Leu Leu Se - #r Pro Asp Lys Asn Pro# 220- Gly Leu Ile Lys Trp Glu Asp Arg Ser Glu Gl - #y Ile Phe Arg Phe Leu225 2 - #30 2 - #35 2 -#40- Lys Ser Glu Ala Val Ala Gln Leu Trp Gly Ly - #s Lys Lys Asn Asn Ser# 255- Ser Met Thr Tyr Glu Lys Leu Ser Arg Ala Me - #t Arg Tyr Tyr Tyr Lys# 270- Arg Glu Ile Leu Glu Arg Val Asp Gly Arg Ar - #g# 280__________________________________________________________________________

Asthma related genes

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Non-Patent Literature Citations (37)

Entry
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Genbank Accession No. AA055327.
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