# Patent

## Title
DNA molecules encoding human NHL, a DNA helicase

## Abstract

The present invention disclosed isolated nucleic acid molecules (polynucleotides) which encode NHL, a putative DNA helicase. The present invention in turn relates to recombinant vectors and recombinant hosts which contain a DNA fragment encoding NHL, substantially purified forms of associated NHL, associated mutant proteins, and methods associated with identifying compounds which modulate NHL, which will be useful in the treatment of various neoplastic disorders. Both a genomic clone containing regulatory and intron sequences, as well as the exon structure and open reading frame of human NHL are disclosed.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a divisional of U.S. Ser. No. 10/148,806, filed Jun. 5, 2002, now U.S. Pat. No. 6,762,042 which is a national stage entry of PCT/US00/33065, international filing date of Dec. 7, 2000, which claims priority to U.S. Ser. No. 60/169,970, filed Dec. 9, 1999.


STATEMENT REGARDING FEDERALLY-SPONSORED R&D
Not Applicable.
REFERENCE TO MICROFICHE APPENDIX
Not Applicable.
FIELD OF THE INVENTION
The present invention relates in part to isolated nucleic acid molecules (polynucleotides) which encode NHL, a putative DNA helicase. The present invention also relates to recombinant vectors and recombinant hosts which contain a DNA fragment encoding NHL, substantially purified forms of associated NHL, associated mutant proteins, and methods associated with identifying compounds which modulate NHL, which will be useful in the treatment of various neoplastic disorders, given that this gene is located at 20q13.3 and immediately adjacent to M68/DcR3, which is involved in tumor growth. Also included within the present invention is a human genomic fragment representing this portion of the human genome, along with three additional genes (M68/DcR3, SCLIP, and ARP).
BACKGROUND OF THE INVENTION
Naumovski et al. (1985, Mol. Cell Biol. 5:17-26; Reynolds et al. (1985 Nucleic Acid Res 13:2357-2372) and Weber et al. (1990 EMBO J. 9:1437-1447) disclose members of the RAD3/ERCC2 gene family of DNA helicases.
It is known that several chemotherapeutic agents inhibit helicases, including actinomycin Cl, daunorubicin and nogalamycin (Tuteja, et al., 1997, Biochem. Biophys. Res. Comm. 236(3):636-640), and a prostate cancer drug, CI-958 (Lun, et al., 1998, Cancer Chemother. Pharmacol. 42(6):447-453). In addition, some topoisomerases have been shown to have anti-cancer activity.
Despite the identification of the aforementioned helicase-encoding genes and chemotherapeutic agents, it would be advantageous to identify additional genes which reside within chromosomal regions associated with a disease state such as cancer as well as a gene which encodes a type of protein which may be associated with that disease. The present invention addresses and meets this need by disclosing a DNA molecule encoding a DNA helicase with a chromosomal location suggestive of association with cancer.
SUMMARY OF THE INVENTION
The present invention relates to an isolated or purified nucleic acid molecule (polynucleotide) which encodes a novel mammalian DNA helicase.
The present invention also relates to an isolated nucleic acid molecule (polynucleotide) which encodes mRNA which expresses a novel human DNA helicase, NHL.
A preferred aspect of the present invention relates to an isolated or purified DNA molecule which encodes human NHL, the nucleotide sequence as set forth in FIG. 1A-B and SEQ ID NO:1.
The present invention also relates to biologically active fragments or mutants of SEQ ID NO:1 which encode a mRNA molecule expressing a novel DNA helicase, NHL. Any such biologically active fragment and/or mutant will encode either a protein or protein fragment which at least substantially mimics the biological properties of the human NHL protein disclosed herein in FIG. 2 and as set forth as SEQ ID NO:2. Any such polynucleotide includes but is not necessarily limited to nucleotide substitutions, deletions, additions, amino-terminal truncations and carboxy-terminal truncations such that these mutations encode mRNA which express a functional NHL protein in a host cell, so as to be useful for screening for agonists and/or antagonists of NHL activity.
The present invention also relates to recombinant vectors and recombinant hosts, both prokaryotic and eukaryotic, which contain the substantially purified nucleic acid molecules disclosed throughout this specification.
The present invention also relates to a substantially purified form of a human NHL protein which comprises the amino acid sequence disclosed in FIG. 2 and set forth as SEQ ID NO:2.
A preferred aspect of this portion of the present invention is a NHL protein which consists of the amino acid sequence disclosed in FIG. 2 and set forth as SEQ ID NO:2.
Another preferred aspect of the present invention relates to a substantially purified NHL protein, preferably a human NHL protein, obtained from a recombinant host cell containing a DNA expression vector comprises a nucleotide sequence as set forth in SEQ ID NO:1 and expresses the respective NHL protein. It is especially preferred is that the recombinant host cell be a eukaryotic host cell, such as a mammalian cell line.
The present invention also relates to biologically active fragments and/or mutants of a NHL protein comprising the amino acid sequence as set forth in SEQ ID NO:2, including but not necessarily limited to amino acid substitutions, deletions, additions, amino terminal truncations and carboxy-terminal truncations such that these mutations provide for proteins or protein fragments of diagnostic, therapeutic or prophylactic use and would be useful for screening for selective modulators, including but not limited to agonists and/or antagonists for human NHL pharmacology.
A preferred aspect of the present invention is disclosed in FIG. 2 and is set forth as SEQ ID NO:2, a respective amino acid sequence which encodes human NHL. Characterization of one or more of these DNA helicase-like proteins allows for screening methods to identify novel NHL modulators that may be useful in the treatment of human neoplastic disorders. The modulators selected through such screening and selection protocols may be used alone or in conjunction with other cancer therapies. As noted above, heterologous expression of a NHL protein will allow the pharmacological analysis of compounds which modulate NHL activity and hence may be useful in various cancer therapies. To this end, heterologous cell lines expressing a NHL protein can be used to establish functional or binding assays to identify novel NHL modulators.
The present invention also relates to polyclonal and monoclonal antibodies raised in response to either the NHL or a biologically active fragment of NHL.
The present invention relates to transgenic mice comprising altered genotypes and phenotypes in relation to NHL and its in vivo activity.
The present invention also relates to NHL fusion constructs, including but not limited to fusion constructs which express a portion of the NHL protein linked to various markers, including but in no way limited to GFP (Green fluorescent protein), the MYC epitope, and GST. Any such fusion constructs may be expressed in the cell line of interest and used to screen for NHL modulators.
Therefore, the present invention relates to methods of expressing mammalian NHL, and preferably human NHL, biological equivalents disclosed herein, assays employing these gene products, recombinant host cells which comprise DNA constructs which express these proteins, and compounds identified through these assays which act as agonists or antagonists of NHL activity.
The present invention also relates to the isolated genomic sequence which comprises SEQ ID NO:1, a 115 kb genomic fragment set forth herein as SEQ ID NO:3. As especially preferred aspect of this portion of the invention is the region of the genomic fragment of SEQ ID NO:3 which comprises the regulatory and coding regions of human NHL, as well as intervening sequences (introns). This 115 kb fragment contains at least the coding region of four genes, NHL, M68/DcR3, SCLIP and ARP. As discussed herein, it has been shown that this region of chromosome 20 is associated with tumor growth. Therefore, an aspect of this invention also comprises the use of one or more regions of this 115 kb genomic sequence to identify compounds which up or downregulate expression of one or more of the genes localized within this 115 kb region, wherein this up or down regulation results in an interference of tumor growth. For example, a transcription element of one of these four genes may be responsible for M68/DcR3 (and/or NHL) overexpression in tumors, and if M68 or NHL overexpression in tumors has a caustic role, blockage of M68/DcR3 or NHL overexpression in tumors by interfering with this transcription site will be useful.
It is an object of the present invention to provide an isolated nucleic acid molecule (e.g., SEQ ID NO:1) which encodes novel form of human NHL, or fragments, mutants or derivatives of human NHL as set forth in FIG. 2 and SEQ ID NO:2. Any such polynucleotide includes but is not necessarily limited to nucleotide substitutions, deletions, additions, amino-terminal truncations and carboxy-terminal truncations such that these mutations encode mRNA which express a protein or protein fragment of diagnostic, therapeutic or prophylactic use and would be useful for screening for selective modulators of human NHL activity.
It is a further object of the present invention to provide the mammalian, and especially human, NHL proteins or protein fragments encoded by the nucleic acid molecules referred to in the preceding paragraph.
It is a further object of the present invention to provide recombinant vectors and recombinant host cells which comprise a nucleic acid sequence encoding mammalian, and especially human, NHL protein and biological equivalent thereof.
It is an object of the present invention to provide a substantially purified form of human NHL, as set forth in FIG. 2 and SEQ ID NO:2.
Is another object of the present invention to provide a substantially purified recombinant form of a NHL protein which has been obtained from a recombinant host cell transformed or transfected with a DNA expression vector which comprises and appropriately expresses a complete open reading frame as set forth in SEQ ID NO:1, resulting in a functional, processed form of NHL. It is especially preferred is that the recombinant host cell be a eukaryotic host cell, such as a mammalian cell line.
It is an object of the present invention to provide for biologically active fragments and/or mutants of mammalian, and especially human, NHL, such as set forth in SEQ ID NO:2, including but not necessarily limited to amino acid substitutions, deletions, additions, amino terminal truncations and carboxy-terminal truncations such that these mutations provide for proteins or protein fragments of diagnostic, therapeutic and/or prophylactic use.
It is also an object of the present invention to use NHL proteins or biological equivalent to screen for modulators, preferably selective modulators, of human NHL activity. Any such compound may be useful in screening for and selecting compounds active against human neoplastic disorders.
As used herein, “substantially free from other nucleic acids” means at least 90%, preferably 95%, more preferably 99%, and even more preferably 99.9%, free of other nucleic acids. Thus, a human NHL DNA preparation that is substantially free from other nucleic acids will contain, as a percent of its total nucleic acid, no more than 10%, preferably no more than 5%, more preferably no more than 1%, and even more preferably no more than 0.1%, of non-NHL nucleic acids. Whether a given NHL DNA preparation is substantially free from other nucleic acids can be determined by such conventional techniques of assessing nucleic acid purity as, e.g., agarose gel electrophoresis combined with appropriate staining methods, e.g., ethidium bromide staining, or by sequencing.
As used herein, “substantially free from other proteins” or “substantially purified” means at least 90%, preferably 95%, more preferably 99%, and even more preferably 99.9%, free of other proteins. Thus, a NHL protein preparation that is substantially free from other proteins will contain, as a percent of its total protein, no more than 10%, preferably no more than 5%, more preferably no more than 1%, and even more preferably no more than 0.1%, of non-NHL proteins. Whether a given NHL protein preparation is substantially free from other proteins can be determined by such conventional techniques of assessing protein purity as, e.g., sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) combined with appropriate detection methods, e.g., silver staining or immunoblotting. As used interchangeably with the terms “substantially free from other proteins” or “substantially purified”, the terms “isolated NHL protein” or “purified NHL protein” also refer to NHL protein that has been isolated from a natural source. Use of the term “isolated” or “purified” indicates that NHL protein has been removed from its normal cellular environment. Thus, an isolated NHL protein may be in a cell-free solution or placed in a different cellular environment from that in which it occurs naturally. The term isolated does not imply that an isolated NHL protein is the only protein present, but instead means that an isolated NHL protein is substantially free of other proteins and non-amino acid material (e.g., nucleic acids, lipids, carbohydrates) naturally associated with the NHL protein in vivo. Thus, a NHL protein that is recombinantly expressed in a prokaryotic or eukaryotic cell and substantially purified from this host cell which does not naturally (i.e., without intervention) express this protein is of course “isolated NHL protein” under any circumstances referred to herein. As noted above, a NHL protein preparation that is an isolated or purified NHL protein will be substantially free from other proteins will contain, as a percent of its total protein, no more than 10%, preferably no more than 5%, more preferably no more than 1%, and even more preferably no more than 0.1%, of non-NHL proteins.
As used interchangeably herein, “functional equivalent” or “biologically active equivalent” means a protein which does not have exactly the same amino acid sequence as naturally occurring NHL, due to alternative splicing, deletions, mutations, substitutions, or additions, but retains substantially the same biological activity as NHL. Such functional equivalents will have significant amino acid sequence identity with naturally occurring NHL and genes and cDNA encoding such functional equivalents can be detected by reduced stringency hybridization with a DNA sequence encoding naturally occurring NHL. For example, a naturally occurring NHL disclosed herein comprises the amino acid sequence shown as SEQ ID NO:2 and is encoded by SEQ ID NO:1. A nucleic acid encoding a functional equivalent has at least about 50% identity at the nucleotide level to SEQ ID NO:1.
As used herein, “a conservative amino acid substitution” refers to the replacement of one amino acid residue by another, chemically similar, amino acid residue. Examples of such conservative substitutions are: substitution of one hydrophobic residue (isoleucine, leucine, valine, or methionine) for another; substitution of one polar residue for another polar residue of the same charge (e.g., arginine for lysine; glutamic acid for aspartic acid).
As used herein, the term “mammalian” will refer to any mammal, including a human being.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1A-B shows the nucleotide sequence which comprises the open reading frame which encodes human NHL, the nucleotide sequence set forth as SEQ ID NO:1. The initiating Met residue (ATG) and the stop codon (TAG) are underlined.
FIG. 2 shows the amino acid sequence of human NHL as set forth in SEQ ID NO:2.
FIG. 3 shows the alignment of amino acid sequences of human NHL to ERCC2/RAD3 gene family members. Rep D (Dictyosteliem discoideum); RAD 3 (S. cerevisiae); RAD 15 (S. pombe) and XP_GroupD (Homo sapien).
FIG. 4 shows Northern analysis of NHL expression in multi-human tissues.
FIG. 5A-B show the genomic structure of the NHL gene (FIG. 5A) and the entire 115 kb genomic region (FIG. 5B) containing the NHL, M68/DcR3, SCLIP and ARP genes.



DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to an isolated or purified nucleic acid molecule (polynucleotide) which encodes a novel mammalian DNA helicase. An especially preferred aspect of this invention relates to an isolated nucleic acid molecule (polynucleotide) which encodes mRNA which expresses a novel human DNA helicase, NHL.
The gene M68/DcR3 is a secreted TNFR member that is overexpressed in a number of human tumors. M68/DcR3 is located at 20q13.3, a known site that is associated with frequent gene amplification in cancer. M68/DcR3 protein binds to FASL and inhibit FAS mediated apoptosis. Thus, genes tightly linked to M68/DcR3 may be coregulated (e.g. co overexpressed and/or amplified in tumors). During the course of cloning the genomic M68/DcR3 fragment and identifying genes that are linked to M68/DcR3 at 20q13.3, three genes, including a novel gene that is similar to the Rad3/ERCC2 helicase family, were identified (termed NHL) in the immediately adjacent (overlapping) region. Given NHL's chromosomal location and the frequent association of DNA helicases with human genetic disorders (mutations in DNA helicases have been found associated with multiple diseases, including xeroderma pigmentosum, Cockayne's syndrome, Bloom's syndrome, and Werner's syndrome), NHL is a candidate for contribution to certain human neoplastic disorders. To this end, the genomic clone for this gene is disclosed and the complete sequence is determined. The transcript was identified through exon prediction using GRAIL2 and sequence alignment to a contiguous 4.5 kilobase region of chromosome 4 (88% sequence identity). The complete exon structure of NHL was subsequently confirmed by RT-PCR analysis. Multiple sequence alignment of NHL to known helicases showed that NHL contains all the seven critical helicase domains. BLAST analysis of the predicted 1,219 amino acid sequence revealed an approximately 26% sequence identity and 48% sequence similarity to the RAD3/ERCC2 gene family of DNA helicases (Naumovski et al., 1985 Mol. Cell Biol. 5:17-26; Reynolds et al., 1985 Nucleic Acid Res 13:2357-72; Weber et al., 1990 EMBO J. 9:1437-1447). The mRNA expression pattern of NHL was also examined in multiple human tissues. Radiation hybrid chromosomal mapping reconfirms that it is linked to M68/DcR3 locus.
A preferred aspect of the present invention relates to an isolated or purified DNA molecule which encodes human NHL, the nucleotide sequence as set forth in FIG. 1A-B and SEQ ID NO:1, which is as follows:









AGTCAGCCCT GCTGCCAGCC AGTGCCGGGT GCTGGGGACT CAGGGAGGCC CGCCGGGACC
(SEQ ID NO:1)



 


ACTGCGGGAC AGTGAGCCGA GCAGAAGCTG GAACGCAGGA GAGGAAGGAG AGGGGGCGGT


 


CAGGGCTCTC AGGAGCCGGG TCCTGGGCAA GGCGCAGCCG TTTTCAAATT TTCAGGAAAG


 


CGGTCGGCTC ACACTCGAGC AGTAAAAAGA TGCCTCTGGG GAGGAGGCCC GTGCAGCTCT


 


CCGGGCAATG GTGGTGGCTC GGCCTAGAGA GGCGGTAGTG GAACGCAGAC CCTGGTGGGG


 


GAATGACATC AAGGGAGGAG ACGGGCGGGA CCCCAGATTT CTGCCTGTGG GCGATGGAAG


 


TGAGGTTCAC TGGCCAGCGG AGCCGGACAC AGAACGCGCA AAACGCCGTG TAGGCCTGGA


 


GGAGCCGAAG AGCAGGCGGA CCCCCTCCGC GGGGGAACAG TTTCCGCCGG GAGCACAAAG


 


CAACGGACCG GAAGTGGGGG GCGGAAGTGC AGTGGGCTCA GCGCCGACTG CGCGCCTCTG


 


CCCGCGAAAA CTCTGAGCTG GCTGACAGCT GGGGACGGGT GGCGGCCCTC GACTGGAGTC


 


GGTTGAGTTC CTGAGGGACC CCGGTTCTGG AAGGTTCGCC GCGGAGACAA GTGAGCAGTC


 


TGTGCCATAG GGATTCTCGA AGAGAACAGC GTTGTGTCCC AGTGCACATG CTCGCATCGC


 


TTACCAGGAG TGCCCGAGAC CCTAAGATGT TCGGAGTGGT TTTTTCGCAC AGACCCGAAT


 


AGCCTGCCCC TCAGCCACGC TCTGTGCCCT TCTGAGAACA GGCTGATATG CCCAAGATAG


 


TCCTGAATGG TGTGACCGTA GACTTCCCTT TCCAGCCCTA CAAATGCCAA CAGGAGTACA


 


TGACCAAGGT CCTGGAATGT CTGCAGCAGA AGGTGAATGG CATCCTGGAG AGCCCTACGG


 


GTACAGGGAA GACGCTGTGC CTGCTGTGCA CCACGCTGGC CTGGCGAGAA CACCTCCGAG


 


ACGGCATCTC TGCCCGCAAG ATTGCCGAGA GGGCGCAAGG AGAGCTTTTC CCGGATCGGG


 


CCTTGTCATC CTGGGGCAAC GCTGCTGCTG CTGCTGGAGA CCCCATAGCT TGCTACACGG


 


ACATCCCAAA GATTATTTAC GCCTCCAGGA CCCACTCGCA ACTCACACAG GTCATCAACG


 


AGCTTCGGAA CACCTCCTAC CGGCCTAAGG TGTGTGTGCT GGGCTCCCGG GAGCAGCTGT


 


GCATCCATCC TGAGGTGAAG AAACAAGAGA GTAACCATCT ACAGATCCAC TTGTGCCGTA


 


AGAAGGTGGC AAGTCGCTCC TGTCATTTCT ACAACAACGT AGAAGAAAAA AGCCTGGAGC


 


AGGAGCTGGC CAGCCCCATC CTGGACATTG AGGACTTGGT CAAGAGCGGA AGCAAGCACA


 


GGGTGTGCCC TTACTACCTG TCCCGGAACC TGAAGCAGCA AGCCGACATC ATATTCATGC


 


CGTACAATTA CTTGTTGGAT GCCAAGAGCC GCAGAGCACA CAACATTGAC CTGAAGGGGA


 


CAGTCGTGAT CTTTGACGAA GCTCACAACG TGGAGAAGAT GTGTGAAGAA TCGGCATCCT


 


TTGACCTGAC TCCCCATGAC CTGGCTTCAG GACTGGACGT CATAGACCAG GTGCTGGAGG


 


AGCAGACCAA GGCAGCGCAG CAGGGTGAGC CCCACCCGGA GTTCAGCGCG GACTCCCCCA


 


GCCCAGGGCT GAACATGGAG CTGGAAGACA TTGCAAAGCT GAAGATGATC CTGCTGCGCC


 


TGGAGGGGGC CATCGATGCT GTTGAGCTGC CTGGAGACGA CAGCGGTGTC ACCAAGCCAG


 


GGAGCTACAT CTTTGAGCTG TTTGCTGAAC CCCAGATCAC GTTTCAGACC AAGGGCTGCA


 


TCCTGGACTC GCTGGACCAG ATCATCCAGC ACCTGGCAGG ACGTGCTGGA GTGTTCACCA


 


ACACGGCCGG ACTGCAGAAG CTGGCGGACA TTATCCAGAT TGTGTTCAGT GTGGACCCCT


 


CCGAGGGCAG CCCTGGTTCC CCAGCAGGGC TGGGGGCCTT ACAGTCCTAT AAGGTGCACA


 


TCCATCCTGA TGCTGGTCAC CGGAGGACGG CTCAGCGGTC TGATGCCTGG AGCACCACTG


 


CAGCCAGAAA GCGAGGGAAG GTGCTGAGCT ACTGGTGCTT CAGTCCCGGC CACAGCATGC


 


ACGAGCTGGT CCGCCAGGGC GTCCGCTCCC TCATCCTTAC CAGCGGCACG CTGGCCCCGG


 


TGTCCTCCTT TGCTCTGGAG ATGCAGATCC CTTTCCCAGT CTGCCTGGAG AACCCACACA


 


TCATCGACAA GCACCAGATC TGGGTGGGGG TCGTCCCCAG AGGCCCCGAT GGAGCCCAGT


 


TGAGCTCCGC GTTTGACAGA CGGTTTTCCG AGGAGTGCTT ATCCTCCCTG GGGAAGGCTC


 


TGGGCAACAT CGCCCGCGTG GTGCCCTATG GGCTCCTGAT CTTCTTCCCT TCCTATCCTG


 


TCATGGAGAA GAGCCTGGAG TTCTGGCGGG CCCGCGACTT GGCCAGGAAG ATGGAGGCGC


 


TGAAGCCGCT GTTTGTGGAG CCCAGGAGCA AAGGCAGCTT CTCCGAGACC ATCAGTGCTT


 


ACTATGCAAG GGTTGCCGCC CCTGGGTCCA CCGGCGCCAC CTTCCTGGCG GTCTGCCGGG


 


GCAAGGCCAG CGAGGGGCTG GACTTCTCAG ACACGAATGG CCGTGGTGTG ATTGTCACGG


 


GCCTCCCGTA CCCCCCACGC ATGGACCCCC GGGTTGTCCT CAAGATGCAG TTCCTGGATG


 


AGATGAAGGG CCAGGGTGGG GCTGGGGGCC AGTTCCTCTC TGGGCAGGAG TGGTACCGGC


 


AGCAGGCGTC CAGGGCTGTG AACCAGGCCA TCGGGCGAGT GATCCGGCAC CGCCAGGACT


 


ACGGAGCTGT CTTCCTCTGT GACCACAGGT TCGCCTTTGC CGACGCAAGA GCCCAACTGC


 


CCTCCTGGGT GCGTCCCCAC GTCAGGGTGT ATGACAACTT TGGCCATGTC ATCCGAGACG


 


TGGCCCAGTT CTTCCGTGTT GCCGAGCGAA CTATGCCAGC GCCGGCCCCC CGGGCTACAG


 


CACCCAGTGT GCGTGGAGAA GATGCTGTCA GCGAGGCCAA GTCGCCTGGC CCCTTCTTCT


 


CCACCAGGAA AGCTAAGAGT CTGGACCTGC ATGTCCCCAG CCTGAAGCAG AGGTCCTCAG


 


GGTCACCAGC TGCCGGGGAC CCCGAGAGTA GCCTGTGTGT GGAGTATGAG CAGGAGCCAG


 


TTCCTGCCCG GCAGAGGCCC AGGGGGCTGC TGGCCGCCCT GGAGCACAGC GAACAGCGGG


 


CGGGGAGCCC TGGCGAGGAG CAGGCCCACA GCTGCTCCAC CCTGTCCCTC CTGTCTGAGA


 


AGAGGCCGGC AGAACAACCG CGAGGAGGGA GGAAGAAGAT CCGGCTGGTC AGCCACCCGG


 


AGGAGCCCGT GGCTGGTGCA CAGACGGACA GGGCCAAGCT CTTCATGGTG GCCGTGAAGC


 


AGGAGTTGAG CCAAGCCAAC TTTGCCACCT TCACCCAGGC CCTGCAGGAC TACAAGGGTT


 


CCGATGACTT CGCCGCCCTG GCCGCCTGTC TCGGCCCCCT CTTTGCTGAG GACCCCAAGA


 


AGCACAACCT GCTCCAAGGC TTCTACCAGT TTGTGCGGCC CCACCATAAG CAGCAGTTTG


 


AGGAGGTCTG TATCCAGCTG ACAGGACGAG GCTGTGGCTA TCGGCCTGAG CACAGCATTC


 


CCCGAAGGCA GCGGGCACAG CCGGTCCTGG ACCCCACTGG AAGAACGGCG CCGGATCCCA


 


AGCTGACCGT GTCCACGGCT GCAGCCCAGC AGCTGGACCC CCAAGAGCAC CTGAACCAGG


 


GCAGGCCCCA CCTGTCGCCC AGGCCACCCC CAACAGGAGA CCCTGGCAGC CAACCACAGT


 


GGGGGTCTGG AGTGCCCAGA GCAGGGAAGC AGGGCCAGCA CGCCGTGAGC GCCTACCTGG


 


CTGATGCCCG CAGGGCCCTG GGGTCCGCGG GCTGTAGCCA ACTCTTGGCA GCGCTGACAG


 


CCTATAAGCA AGACGACGAC CTCGACAAGG TGCTGGCTGT GTTGGCCGCC CTGACCACTG


 


CAAAGCCAGA GGACTTCCCC CTGCTGCACA GGTTCAGCAT GTTTGTGCGT CCACACCACA


 


AGCAGCGCTT CTCACAGACG TGCACAGACC TGACCGGCCG GCCCTACCCG GGCATGGAGC


 


CACCGGGACC CCAGGAGGAG AGGCTTGCCG TGCCTCCTGT GCTTACCCAC AGGGCTCCCC


 


AACCAGGCCC CTCACGGTCC GAGAAGACCG GGAAGACCCA GAGCAAGATC TCGTCCTTCC


 


TTAGACAGAC GCCAGCAGGG ACTGTGGGGG CGGGCGGTGA GGATGCAGGT CCCAGCCAGT


 


CCTCAGGACC TCCCCACGGG CCTGCAGCAT CTGAGTGGGG CCTCTAGGAT GTGCCCAGCC


 


TGCCACACCG CCTCCAGGAA GCAGAGCGTC ATGCAGGTCT TCTGGCCAGA GCCCCAGTGA


 


GTGCCCACGG AGGCCCCCAG CACACCCAAC GTGGCTTGAT CACCTGCCTG TCCAGCTCTG


 


GTGGGCCAAG AACCCACCCA ACAGAATAGG CCAGCCCATG CCAGCCGGCT TGGCCCGCTG


 


CAGGCCTCAG GCAGGCGGGG CCCATGGTTG GTCCCTGCGG TGGGACCGGA TCTGGGCCTG


 


CCTCTGAGAA GCCCTGAGCT ACCTTGGGGT CTGGGGTGGG TTTCTGGGAA AGTGCTTCCC


 


CAGAACTTCC CTGGCTCCTG GCCTGTGAGT GGTGCCACAG GGGCACCCCA GCTGAGCCCC


 


TCACCGGGAA GGAGGAGACC CCCGTGGGCA CGTGTCCACT TTTAATCAGG GGACAGGGCT


 


CTCTAATAAA GCTGCTGGCA GTGCCC.






The above-exemplified isolated DNA molecule shown in FIG. 1A-B and SEQ ID NO:1 comprise 4946 nucleotides, with an initiating Met at nucleotides 828-830 and a “TAG” termination codon at nucleotides 4485-4487. The initiating Met and TAG termination codon are underlined.
The present invention also relates to biologically active fragments or mutants of SEQ ID NO:1 which encode a mRNA molecule expressing a novel DNA helicase, NHL. Any such biologically active fragment and/or mutant will encode either a protein or protein fragment which at least substantially mimics the biological properties of the human NHL protein disclosed herein in FIG. 2 and as set forth as SEQ ID NO:2. Any such polynucleotide includes but is not necessarily limited to nucleotide substitutions, deletions, additions, amino-terminal truncations and carboxy-terminal truncations such that these mutations encode mRNA which express a functional NHL protein in a host cell, so as to be useful for screening for agonists and/or antagonists of NHL activity.
The isolated nucleic acid molecules of the present invention may include a deoxyribonucleic acid molecule (DNA), such as genomic DNA and complementary DNA (cDNA), which may be single (coding or noncoding strand) or double stranded, as well as synthetic DNA, such as a synthesized, single stranded polynucleotide. The isolated nucleic acid molecule of the present invention may also include a ribonucleic acid molecule (RNA).
The present invention also relates to recombinant vectors and recombinant hosts, both prokaryotic and eukaryotic, which contain the substantially purified nucleic acid molecules disclosed throughout this specification.
The degeneracy of the genetic code is such that, for all but two amino acids, more than a single codon encodes a particular amino acid. This allows for the construction of synthetic DNA that encodes the NHL protein where the nucleotide sequence of the synthetic DNA differs significantly from the nucleotide sequence of SEQ ID NO:1 but still encodes the same NHL protein as SEQ ID NO:2. Such synthetic DNAs are intended to be within the scope of the present invention. If it is desired to express such synthetic DNAs in a particular host cell or organism, the codon usage of such synthetic DNAs can be adjusted to reflect the codon usage of that particular host, thus leading to higher levels of expression of the NHL protein in the host. In other words, this redundancy in the various codons which code for specific amino acids is within the scope of the present invention. Therefore, this invention is also directed to those DNA sequences which encode RNA comprising alternative codons which code for the eventual translation of the identical amino acid, as shown below:

    A=Ala=Alanine: codons GCA, GCC, GCG, GCU
    C=Cys=Cysteine: codons UGC, UGU
    D=Asp=Aspartic acid: codons GAC, GAU
    E=Glu=Glutamic acid: codons GAA, GAG
    F=Phe=Phenylalanine: codons UUC, UUU
    G=Gly=Glycine: codons GGA, GGC, GGG, GGU
    H=His=Histidine: codons CAC, CAU
    I=Ile=Isoleucine: codons AUA, AUC, AUU
    K=Lys=Lysine: codons AAA, AAG
    L=Leu=Leucine: codons UUA, UUG, CUA, CUC, CUG, CUU
    M=Met=Methionine: codon AUG
    N=Asp=Asparagine: codons AAC, AAU
    P=Pro=Proline: codons CCA, CCC, CCG, CCU
    Q=Gln=Glutamine: codons CAA, CAG
    R=Arg=Arginine: codons AGA, AGG, CGA, CGC, CGG, CGU
    S=Ser=Serine: codons AGC, AGU, UCA, UCC, UCG, UCU
    T=Thr=Threonine: codons ACA, ACC, ACG, ACU
    V=Val=Valine: codons GUA, GUC, GUG, GUU
    W=Trp=Tryptophan: codon UGG
    Y=Tyr=Tyrosine: codons UAC, UAU

Therefore, the present invention discloses codon redundancy which may result in differing DNA molecules expressing an identical protein. For purposes of this specification, a sequence bearing one or more replaced codons will be defined as a degenerate variation. Also included within the scope of this invention are mutations either in the DNA sequence or the translated protein which do not substantially alter the ultimate physical properties of the expressed protein. For example, substitution of valine for leucine, arginine for lysine, or asparagine for glutamine may not cause a change in functionality of the polypeptide.



It is known that DNA sequences coding for a peptide may be altered so as to code for a peptide having properties that are different than those of the naturally occurring peptide. Methods of altering the DNA sequences include but are not limited to site directed mutagenesis. Examples of altered properties include but are not limited to changes in the affinity of an enzyme for a substrate or a receptor for a ligand.
The present invention also relates to recombinant vectors and recombinant hosts, both prokaryotic and eukaryotic, which contain the substantially purified nucleic acid molecules disclosed throughout this specification. The nucleic acid molecules of the present invention encoding a NHL protein, in whole or in part, can be linked with other DNA molecules, i.e, DNA molecules to which the NHL coding sequence are not naturally linked, to form “recombinant DNA molecules” which encode a respective NHL protein. The novel DNA sequences of the present invention can be inserted into vectors which comprise nucleic acids encoding NHL or a functional equivalent. These vectors may be comprised of DNA or RNA; for most cloning purposes DNA vectors are preferred. Typical vectors include plasmids, modified viruses, bacteriophage, cosmids, yeast artificial chromosomes, and other forms of episomal or integrated DNA that can encode a NHL protein. It is well within the purview of the skilled artisan to determine an appropriate vector for a particular gene transfer or other use.
Included in the present invention are DNA sequences that hybridize to SEQ ID NO:1 under stringent conditions. By way of example, and not limitation, a procedure using conditions of high stringency is as follows: Prehybridization of filters containing DNA is carried out for 2 hours to overnight at 65° C. in buffer composed of 6×SSC, 5× Denhardt's solution, and 100 μg/ml denatured salmon sperm DNA. Filters are hybridized for 12 to 48 hrs at 65° C. in prehybridization mixture containing 100 μg/ml denatured salmon sperm DNA and 5-20×106 cpm of 32P-labeled probe. Washing of filters is done at 37° C. for 1 hr in a solution containing 2×SSC, 0.1% SDS. This is followed by a wash in 0.1×SSC, 0.1% SDS at 50° C. for 45 min. before autoradiography. Other procedures using conditions of high stringency would include either a hybridization step carried out in 5×SSC, 5× Denhardt's solution, 50% formamide at 42° C. for 12 to 48 hours or a washing step carried out in 0.2×SSPE, 0.2% SDS at 65° C. for 30 to 60 minutes.
Reagents mentioned in the foregoing procedures for carrying out high stringency hybridization are well known in the art. Details of the composition of these reagents can be found in, e.g., Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual; Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. In addition to the foregoing, other conditions of high stringency which may be used are well known in the art.
The present invention also relates to a substantially purified form of a human NHL protein which comprises the amino acid sequence (1219 amino acid residues) disclosed in FIG. 2 and set forth as SEQ ID NO:2. A preferred aspect of this portion of the present invention is a NHL protein which consists of the amino acid sequence disclosed in FIG. 2 and set forth as SEQ ID NO:2, as follows:









MPKIVLNGVT VDFPFQPYKC QQEYMTKVLE CLQQKVNGIL ESPTGTGKTL CLLCTTLAWR
(SEQ ID NO:2)



 


EHLRDGISAR KIAERAQGEL FPDRALSSWG NAAAAAGDPI ACYTDIPKII YASRTHSQLT


 


QVINELRNTS YRPKVCVLGS REQLCIHPEV KKQESNHLQI HLCRKKVASR SCHFYNNVEE


 


KSLEQELASP ILDIEDLVKS GSKHRVCPYY LSRNLKQQAD IIFMPYNYLL DAKSRRAHNI


 


DLKGTVVIFD EAHNVEKMCE ESASFDLTPH DLASGLDVID QVLEEQTKAA QQGEPHPEFS


 


ADSPSPGLNM ELEDIAKLKN ILLRLEGAID AVELPGDDSG VTKPGSYIFE LFAEAQITFQ


 


TKGCILDSLD QIIQHLAGRA GVFTNTAGLQ KLADIIQIVF SVDPSEGSPG SPAGLGALQS


 


YKVHIHPDAG HRRTAQRSDA WSTTAARKRG KVLSYWCFSP GHSMHELVRQ GVRSLILTSG


 


TLAPVSSFAL EMQIPFPVCL ENPHIIDKHQ IWVGVVPRGP DGAQLSSAFD RRFSEECLSS


 


LGKALGNIAR VVPYGLLIFF PSYPVMEKSL EFWRARDLAR KMEALKPLFV EPRSKGSFSE


 


TISAYYARVA APGSTGATFL AVCRGKASEG LDFSDTNGRG VIVTGLPYPP RMDPRVVLKM


 


QFLDEMKGQG GAGGQFLSGQ EWYRQQASRA VNQAIGRVIR HRQDYGAVFL CDHRFAFADA


 


RAQLPSWVRP HVRVYDNFGH VIRDVAQFFR VAERTMPAPA PRATAPSVRG EDAVSEAKSP


 


GPFFSTRKAK SLDLHVPSLK QRSSGSPAAG DPESSLCVEY EQEPVPARQR PRGLLAALEH


 


SEQRAGSPGE EQAHSCSTLS LLSEKRPAEE PRGGRKKIRL VSHPEEPVAG AQTDRAKLFM


 


VAVKQELSQA NFATFTQALQ DYKGSDDFAA LAACLGPLFA EDPKKHNLLQ GFYQFVRPHH


 


KQQFEEVCIQ LTGRGCGYRP EHSIPRRQRA QPVLDPTGRT APDPKLTVST AAAQQLDPQE


 


HLNQGRPHLS PRPPPTGDPG SQPQWGSGVP RAGKQGQHAV SAYLADARRA LGSAGCSQLL


 


AALTAYKQDD DLDKVLAVLA ALTTAKPEDF PLLHRFSMFV RPHHKQRFSQ TCTDLTGRPY


 


PGMEPPGPQE ERLAVPPVLT HRAPQPGPSR SEKTGKTQSK ISSFLRQRPA GTVGAGGEDA


 


GPSQSSGPPH GPAASEWGL*.






The present invention also relates to biologically active fragments and/or mutants of the human NHL protein comprising the amino acid sequence as set forth in SEQ ID NO:2, including but not necessarily limited to amino acid substitutions, deletions, additions, amino terminal truncations and carboxy-terminal truncations such that these mutations provide for proteins or protein fragments of diagnostic, therapeutic or prophylactic use and would be useful for screening for agonists and/or antagonists of NHL function.
Another preferred aspect of the present invention relates to a substantially purified, fully processed NHL protein obtained from a recombinant host cell containing a DNA expression vector which comprises a nucleotide sequence as set forth in SEQ ID NO:1 and expresses the human NHL protein. It is especially preferred is that the recombinant host cell be a eukaryotic host cell, such as a mammalian cell line.
As with many proteins, it is possible to modify many of the amino acids of NHL protein and still retain substantially the same biological activity as the wild type protein. Thus this invention includes modified NHL polypeptides which have amino acid deletions, additions, or substitutions but that still retain substantially the same biological activity as a respective, corresponding NHL. It is generally accepted that single amino acid substitutions do not usually alter the biological activity of a protein (see, e.g., Molecular Biology of the Gene, Watson et al., 1987, Fourth Ed., The Benjamin/Cummings Publishing Co., Inc., page 226; and Cunningham & Wells, 1989, Science 244:1081-1085). Accordingly, the present invention includes a polypeptide where one amino acid substitution has been made in SEQ ID NO:2 wherein the polypeptide still retains substantially the same biological activity as a corresponding NHL protein. The present invention also includes polypeptides where two or more amino acid substitutions have been made in SEQ ID NO:2 wherein the polypeptide still retains substantially the same biological activity as a corresponding NHL protein. In particular, the present invention includes embodiments where the above-described substitutions are conservative substitutions.
One skilled in the art would also recognize that polypeptides that are functional equivalents of NHL and have changes from the NHL amino acid sequence that are small deletions or insertions of amino acids could also be produced by following the same guidelines, (i.e, minimizing the differences in amino acid sequence between NHL and related proteins. Small deletions or insertions are generally in the range of about 1 to 5 amino acids). The effect of such small deletions or insertions on the biological activity of the modified NHL polypeptide can easily be assayed by producing the polypeptide synthetically or by making the required changes in DNA encoding NHL and then expressing the DNA recombinantly and assaying the protein produced by such recombinant expression.
The present invention also includes truncated forms of NHL which contain the region comprising the active site of the enzyme. Such truncated proteins are useful in various assays described herein, for crystallization studies, and for structure-activity-relationship studies.
The present invention also relates to isolated nucleic acid molecules which are fusion constructions expressing fusion proteins useful in assays to identify compounds which modulate wild-type NHL activity, as well as generating antibodies against NHL. One aspect of this portion of the invention includes, but is not limited to, glutathione S-transferase (GST)-NHL fusion constructs. Recombinant GST-NHL fusion proteins may be expressed in various expression systems, including Spodoptera frugiperda (Sf21) insect cells (Invitrogen) using a baculovirus expression vector (pAcG2T, Pharmingen). Another aspect involves NHL fusion constructs linked to various markers, including but not limited to GFP (Green fluorescent protein), the MYC epitope, and GST. Again, any such fusion constructs may be expressed in the cell line of interest and used to screen for modulators of one or more of the NHL proteins disclosed herein.
Any of a variety of procedures may be used to clone NHL. These methods include, but are not limited to, (1) a RACE PCR cloning technique (Frohman, et al., 1988, Proc. Natl. Acad. Sci. USA 85: 8998-9002). 5′ and/or 3′ RACE may be performed to generate a full-length cDNA sequence. This strategy involves using gene-specific oligonucleotide primers for PCR amplification of NHL cDNA. These gene-specific primers are designed through identification of an expressed sequence tag (EST) nucleotide sequence which has been identified by searching any number of publicly available nucleic acid and protein databases; (2) direct functional expression of the NHL cDNA following the construction of a NHL-containing cDNA library in an appropriate expression vector system; (3) screening a NHL-containing cDNA library constructed in a bacteriophage or plasmid shuttle vector with a labeled degenerate oligonucleotide probe designed from the amino acid sequence of the NHL protein; (4) screening a NHL-containing cDNA library constructed in a bacteriophage or plasmid shuttle vector with a partial cDNA encoding the NHL protein. This partial cDNA is obtained by the specific PCR amplification of NHL DNA fragments through the design of degenerate oligonucleotide primers from the amino acid sequence known for other kinases which are related to the NHL protein; (5) screening a NHL-containing cDNA library constructed in a bacteriophage or plasmid shuttle vector with a partial cDNA or oligonucleotide with homology to a mammalian NHL protein. This strategy may also involve using gene-specific oligonucleotide primers for PCR amplification of NHL cDNA identified as an EST as described above; or (6) designing 5′ and 3′ gene specific oligonucleotides using SEQ ID NO:1 as a template so that either the full-length cDNA may be generated by known RACE techniques, or a portion of the coding region may be generated by these same known RACE techniques to generate and isolate a portion of the coding region to use as a probe to screen one of numerous types of cDNA and/or genomic libraries in order to isolate a full-length version of the nucleotide sequence encoding NHL.
It is readily apparent to those skilled in the art that other types of libraries, as well as libraries constructed from other cell types-or species types, may be useful for isolating a NHL-encoding DNA or a NHL homologue. Other types of libraries include, but are not limited to, cDNA libraries derived from other cells.
It is readily apparent to those skilled in the art that suitable cDNA libraries may be prepared from cells or cell lines which have NHL activity. The selection of cells or cell lines for use in preparing a cDNA library to isolate a cDNA encoding NHL may be done by first measuring cell-associated NHL activity using any known assay available for such a purpose.
Preparation of cDNA libraries can be performed by standard techniques well known in the art. Well known cDNA library construction techniques can be found for example, in Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual; Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. Complementary DNA libraries may also be obtained from numerous commercial sources, including but not limited to Clontech Laboratories, Inc. and Stratagene.
It is also readily apparent to those skilled in the art that DNA encoding NHL may also be isolated from a suitable genomic DNA library. Construction of genomic DNA libraries can be performed by standard techniques well known in the art. Well known genomic DNA library construction techniques can be found in Sambrook, et al., supra. One may prepare genomic libraries, especially in P1 artificial chromosome vectors, from which genomic clones containing the NHL gene can be isolated, using probes based upon the NHL nucleotide sequences disclosed herein. Methods of preparing such libraries are known in the art (Ioannou et al., 1994, Nature Genet. 6:84-89).
In order to clone a NHL gene by one of the preferred methods, the amino acid sequence or DNA sequence of a NHL or a homologous protein may be necessary. To accomplish this, a respective NHL protein may be purified and the partial amino acid sequence determined by automated sequenators. It is not necessary to determine the entire amino acid sequence, but the linear sequence of two regions of 6 to 8 amino acids can be determined for the PCR amplification of a partial NHL DNA fragment. Once suitable amino acid sequences have been identified, the DNA sequences capable of encoding them are synthesized. Because the genetic code is degenerate, more than one codon may be used to encode a particular amino acid, and therefore, the amino acid sequence can be encoded by any of a set of similar DNA oligonucleotides. Only one member of the set will be identical to the NHL sequence but others in the set will be capable of hybridizing to NHL DNA even in the presence of DNA oligonucleotides with mismatches. The mismatched DNA oligonucleotides may still sufficiently hybridize to the NHL DNA to permit identification and isolation of NHL encoding DNA. Alternatively, the nucleotide sequence of a region of an expressed sequence may be identified by searching one or more available genomic databases. Gene-specific primers may be used to perform PCR amplification of a cDNA of interest from either a cDNA library or a population of cDNAs. As noted above, the appropriate nucleotide sequence for use in a PCR-based method may be obtained from SEQ ID NO:1 either for the purpose of isolating overlapping 5′ and 3′ RACE products for generation of a full-length sequence coding for NHL, or to isolate a portion of the nucleotide sequence coding for NHL for use as a probe to screen one or more cDNA- or genomic-based libraries to isolate a full-length sequence encoding NHL or NHL-like proteins.
This invention also includes vectors containing a NHL gene, host cells containing the vectors, and methods of making substantially pure NHL protein comprising the steps of introducing the NHL gene into a host cell, and cultivating the host cell under appropriate conditions such that NHL is produced. The NHL so produced may be harvested from the host cells in conventional ways. Therefore, the present invention also relates to methods of expressing the NHL protein and biological equivalents disclosed herein, assays employing these gene products, recombinant host cells which comprise DNA constructs which express these proteins, and compounds identified through these assays which act as agonists or antagonists of NHL activity.
The cloned NHL cDNA obtained through the methods described above may be recombinantly expressed by molecular cloning into an expression vector (such as pcDNA3.neo, pcDNA3.1, pCR2.1, pBlueBacHis2 or pLITMUS28) containing a suitable promoter and other appropriate transcription regulatory elements, and transferred into prokaryotic or eukaryotic host cells to produce recombinant NHL. Expression vectors are defined herein as DNA sequences that are required for the transcription of cloned DNA and the translation of their mRNAs in an appropriate host. Such vectors can be used to express eukaryotic DNA in a variety of hosts such as bacteria, blue green algae, plant cells, insect cells and animal cells. Specifically designed vectors allow the shuttling of DNA between hosts such as bacteria-yeast or bacteria-animal cells. An appropriately constructed expression vector should contain: an origin of replication for autonomous replication in host cells, selectable markers, a limited number of useful restriction enzyme sites, a potential for high copy number, and active promoters. A promoter is defined as a DNA sequence that directs RNA polymerase to bind to DNA and initiate RNA synthesis. A strong promoter is one which causes mRNAs to be initiated at high frequency. To determine the NHL cDNA sequence(s) that yields optimal levels of NHL, cDNA molecules including but not limited to the following can be constructed: a cDNA fragment containing the full-length open reading frame for NHL as well as various constructs containing portions of the cDNA encoding only specific domains of the protein or rearranged domains of the protein. All constructs can be designed to contain none, all or portions of the 5′ and/or 3′ untranslated region of a NHL cDNA. The expression levels and activity of NHL can be determined following the introduction, both singly and in combination, of these constructs into appropriate host cells. Following determination of the NHL cDNA cassette yielding optimal expression in transient assays, this NHL cDNA construct is transferred to a variety of expression vectors (including recombinant viruses), including but not limited to those for mammalian cells, plant cells, insect cells, oocytes, bacteria, and yeast cells. Techniques for such manipulations can be found described in Sambrook, et al., supra, are well known and available to the artisan of ordinary skill in the art. Therefore, another aspect of the present invention includes host cells that have been engineered to contain and/or express DNA sequences encoding the NHL protein. An expression vector containing DNA encoding a NHL-like protein may be used for expression of NHL in a recombinant host cell. Such recombinant host cells can be cultured under suitable conditions to produce NHL or a biologically equivalent form. Expression vectors may include, but are not limited to, cloning vectors, modified cloning vectors, specifically designed plasmids or viruses. Commercially available mammalian expression vectors which may be suitable for recombinant NHL expression, include but are not limited to, pcDNA3.neo (Invitrogen), pcDNA3.1 (Invitrogen), pCI-neo (Promega), pLITMUS28, pLITMUS29, pLITMUS38 and pLITMUS39 (New England Bioloabs), pcDNAI, pcDNAIamp (Invitrogen), pcDNA3 (Invitrogen), pMCIneo (Stratagene), pXT1 (Stratagene), pSG5 (Stratagene), EBO-pSV2-neo (ATCC 37593) pBPV-1(8-2) (ATCC 37110), pdBPV-MMTneo(342-12) (ATCC 37224), pRSVgpt (ATCC 37199), pRSVneo (ATCC 37198), pSV2-dhfr (ATCC 37146), pUCTag (ATCC 37460), and 1ZD35 (ATCC 37565). Also, a variety of bacterial expression vectors may be used to express recombinant NHL in bacterial cells. Commercially available bacterial expression vectors which may be suitable for recombinant NHL expression include, but are not limited to pCR2.1 (Invitrogen), pET11a (Novagen), lambda gt11 (Invitrogen), and pKK223-3 (Pharmacia). In addition, a variety of fungal cell expression vectors may be used to express recombinant NHL in fungal cells. Commercially available fungal cell expression vectors which may be suitable for recombinant NHL expression include but are not limited to pYES2 (Invitrogen) and Pichia expression vector (Invitrogen). Also, a variety of insect cell expression vectors may be used to express recombinant protein in insect cells. Commercially available insect cell expression vectors which may be suitable for recombinant expression of NHL include but are not limited to pBlueBacIII and pBlueBacHis2 (Invitrogen), and pAcG2T (Pharmingen).
Recombinant host cells may be prokaryotic or eukaryotic, including but not limited to, bacteria such as E. coli, fungal cells such as yeast, mammalian cells including, but not limited to, cell lines of bovine, porcine, monkey and rodent origin; and insect cells including but not limited to Drosophila and silkworm derived cell lines. For instance, one insect expression system utilizes Spodoptera frugiperda (Sf21) insect cells (Invitrogen) in tandem with a baculovirus expression vector (pAcG2T, Pharmingen). Also, mammalian species which may be suitable and which are commercially available, include but are not limited to, L cells L-M(TK−) (ATCC CCL 1.3), L cells L-M (ATCC CCL 1.2), Saos-2 (ATCC HTB-85), 293 (ATCC CRL 1573), Raji (ATCC CCL 86), CV-1 (ATCC CCL 70), COS-1 (ATCC CRL 1650), COS-7 (ATCC CRL 1651), CHO-K1 (ATCC CCL 61), 3T3 (ATCC CCL 92), NIH/3T3 (ATCC CRL 1658), HeLa (ATCC CCL 2), C1271 (ATCC CRL 1616), BS-C-1 (ATCC CCL 26), MRC-5 (ATCC CCL 171) and CPAE (ATCC CCL 209).
As disclosed in Example section 1, a 115 kb BAC clone (from Genome Systems) was subcloned and subjected to restriction and sequence analysis. Four genes at chromosome location 20q13.3 were identified, including M68/DcR3, NHL, SCLIP and ARP (FIG. 5A). The nucleotide sequence of this BAC clone, hbm168, is presented as follows:








(SEQ ID NO:3)










TGAAGAGCTT TGACCAAGAG GCTGTGACGA GGCCCTACGA GGACTCTGGC TCTCCTCCTG
60



 


CTAAGCACAC CCAGGCAGGT GTCCTGGCAG ATGAGGACCA CATGCAGAGC CTCGGCCAGC
120


 


CCACCAATGC CCGGATATGC AAGTGAGCCC AGCCTGGACC CCCCGGCGAG GCCCAGCAGC
180


 


ACCAGCCCAG GCCCGAAAAC CTTAAGAAAT GACCAGTGTC TGCTGCTTTA AGCCACCAAG
240


 


CTCTGCGGTG GTTTGTTAGG CTGCAAGCAT GGCTAATTCA GAAACTGCCA GAAACAAGCA
300


 


CTGCTGTCCC CAGCCTGGGA CACACAGGAC CGCCTCTGCG TGGGGAGAGG GCACAGGCTA
360


 


AGGGCACAAA TGCCATCCCA GACCCGGCTC TTGTGTGTGG AAGGGGCCAC TGTGCCATGA
420


 


GGCAGAGGAA ACCTTGGCAG GACCTTATGC CACAGCAATT TAAAAGAGAA GAAACAGGCT
480


 


GGGCGTGGTG GCTCATGCCT ATAATCCCAG CACTTTGGGA GGCCAAGGTG GTGGATCACT
540


 


TGAGGTCAGG AGTTCAAGAC CAGCCTGGCC AATATGGTGA AACCCTGTCT CTACGAAAAA
600


 


TACAAAATTT AGGCAGGCGT GGTGGCGGGT GCCTGTAATC CCTGCTATTC AGGAGGCTGA
660


 


GGCAAGAGAT TTACTTGAAC CCAGGAGGTG GAGGCTGCTG CAGTGAGCTG AGATCATGCC
720


 


ACTGCACTCC AGCCTGTGTG ACGGAGTGAG ACTTGGTCTC AAAAAAAAAA AAGGAAACAC
780


 


ATCTGACTAG TGTGATCTCG CAAGGAACAT TCCAGACACA GTGGAGCTAG AAGGTTCTTC
840


 


TCCAAACAAG GAATCCCCAC GGGATCAAAT TGTTTTGCAT CGGCCAGACA TGGTGGCTCA
900


 


AGCCTGTAAC CCCAGTGCTT CGGGAGGCTG AGGTGGGAGG ACTGCTTGAG TCCAGGAGTT
960


 


CAAGACTAGC TTGGGCAACA CAGTGAGAGC CCATTAGCCA GGCGTGGTGG CACATGCCTG
1020


 


CAGTCCCAGC ACTGTACTAA AAATCTACAC GGGGCCGGGC ATGGTGGCAC ATGCCTGTAG
1080


 


AGTCCCAGCT ACTCAGGAGG CTGAGGCAGG ACGATTCCTT GAACCCAGGA GGTCACGGCT
1140


 


GCCATGAGCC GTGACTGTGC CACTGCACTC CAGTCTGTGC AACAGAACGA GACTCTGTTT
1200


 


CGAAAAACAA AAAATCATTT CATCTCTCCA GTTTCTCCAC TGGCAAAAGA CTCTGTCAAG
1260


 


GTAAAAAATG GTTCTGACCC ACAGAAATCT AAGAAAGGAA AAAATATAAA AAATAGAAAA
1320


 


TTTAAAAAAG AGATGGTCTC AGAATAAAGA CCAACCTGGG CTATGGTTGT CACTCTTCCC
1380


 


TCACACCTTA GAAAGCTTTC TGCCCGCATC TGGCCAAAGG GCCACCCTGC CCCATCTTGG
1440


 


ATCAGTGAGG TGCCTTCGAA CAAGCCACCT GCCCTGGAGC CCGTCCTGTC TTGTCTGCCA
1500


 


CCGCACGCTC AGTAGGGGAG GGGAAGTCGC TAGGTTTTAG TTCACCAGTC TCTGGATCAA
1560


 


GACGTGCCAT AACCAAGAAG CCCCAGCCAC ACCCAGACCC GATGTGGCCA CAAGGGGTCA
1620


 


GCTGGGAAGG CCCAGGAAAA GGCGGGAGGC GGACGAATGG AAATGTCATT CTGTGGCCAC
1680


 


AGAAATGATC TCAACGTTTT GTAACTTCCT ACCAAGAGGC AGTCTTAGCT CTGCCCTTGA
1740


 


ACCAGCACTT GGTGATGTCG CTTGCGTCAA TCAAGGCAAC AGAAGTGAGC AGGAGGCCCA
1800


 


CTTTCCTCTG CAACTGTGGG CTTACGGGGC AAAGAAGTCC AGGCCTCCAG GTGGAGGATC
1860


 


ACAGACCGGG CAAAGCAGAG GAGAGCCACC CAGCCGAGCC TACCTGTGCC TCAGACTGCC
1920


 


TCCCTCCAGA GACCCCTGTG GCCAAGGCCA CCCAGACCAG CAGGTCCTTG CCAAGCTGTC
1980


 


AGCTGACGAC AGGGGTTGGT GAGGCCGGCC CAGACCAGCA GAACCACGAA CCAACCAACA
2040


 


GAATTAAAAA TAATAACAAC TATGTCTTGT CTTAAGCCAC TAAGTTTTGG ATGGTTTCTT
2100


 


TCTTTCTTTT TCTTTTTTTT TTTCGGAGAC GCAGTCTCAC TCTGTTGCCC AGGCTGGAGT
2160


 


GCAGTGGCGC AATCTTGGCT CACTGCAAGC TCTGCCCCCC GGATTCACGC CATTCCCCTG
2220


 


CCTCAGCCTC CTGAGTAACT GGGACTACAG GTGCCTGCCA TTGGGTGTTT TCTTAAACAG
2280


 


CAAAAGAAAA CTGACACAAT CATAAACAGA GCAAGCAAGA GAACTTGGCA ATTATTTCCT
2340


 


CTCTACTTCT CACTGTTCTT CAAAGAGTTA ACTCAAGCAT AAGATGTGAG CAAATTCTTT
2400


 


TAACATCCTA GAAAAAAAGC TCCTACTCAG TGTTCATAAA GCAAAGCTAA CCTACAGGAG
2460


 


CCACCTTCCA CAGTGACCAC AGGAAACCAA GACAGCAAGT GGGACACCAG CCTCCAGGGC
2520


 


ACTGCGCCAG CCGTGCGCCT GTGTCTGCCA CTGCCCTGGT CCGTCACTGC CACCAGCCGG
2580


 


CAAGACACCC ACAGAGGAGA GCTCTAAGCC ACAACTGTGT ACGAAGACAA CTGTGCAGGA
2640


 


TTTTATTACT ACAACATTTT TGTTTTCTTT TTTTTTTTTT TTTGAGACTG AGTCTCGCTC
2700


 


TGTCACCCAG GCTGGAGTGC AGTGGCACAA TCTCGGCTCA CTGTAACCTC CATCTCCCTG
2760


 


GTTCAAGCAA TTCTCCTGCT GCAGCCTCCC AACTGGATTA CAGGCGCCCG CCACCACGCC
2820


 


TGGCTAATTT TTGTACTTTT AGTAGAGATG GGGTTTCACC ATGTTGGCCA GACTGGTCTC
2880


 


AAATTCCTGA CAAGTGATCC ACCCACCCTG GCCTCCCAAA GTGCTGGGAT TACAGGTGTG
2940


 


AGCCACTGCG CCTGGCCCAT TTTTGTTTAT CAATAAAAAT GTACTTAATG TTGAACTCTC
3000


 


CACATTTCAA ATGGGTAACT CCAGTGTCCT TGATGCTCCT GCGACATGTT CGTGAGACTT
3060


 


CTCTTGGGTG TGAGAGTCTA GCATGTGGGT GGTCTGGACA GGAGGGGGAG GGAAGAGTGC
3120


 


AGAGCCGGGC AGGGTAAAGA GACCCCCTAG GATGTGAAGG CCGCCCTGCA TTTGTCAGAC
3180


 


TGGGCAACAC CCACTCCATC AGATGGACCC TGGTATGGGC GGCAAGCCAC CTAGGTGCCG
3240


 


AGGCAAGAGA CCGAGGGCAC GAGCTGTTCC GGTGTAATAA AATGCATAAA ATAAGAATAG
3300


 


TTATACTAGA TATAGATCAT AAATATGATT ATATATGAAT ATCATTCATC ATTAGTTTGT
3360


 


AGCAATTACT CTTTATTCCA ATATTATAAT AATCCTTGCC TAAGCATAAC CTAGGAAAAA
3420


 


CTAGGAAATC ATAACCTAGG AAAAACTAGG CCATACAGAG ATAGGAGCTG AGGGGACATA
3480


 


GTGAGAACTG ACCAGAAGAC AAGAGTGCGA GCCTTCTGTT ATGCCTGGAC AGGGCCACCA
3540


 


GAGGGCTCCT TGGTCTAGCG GTAACGCCAG CATCTGGGAA GACGCCCGTT GCCAAGTGGA
3600


 


CCGTGGTCTA GCGGTAGCCT CAGTGTCAAG GAAAAACACC CGCTACTTAG CAAACCAGGA
3660


 


AAGAGAGTCT CCCTTTCCCC GGGGGAGTTT AGAGAAGACT CTACTCCTCC ACCTCTTGCG
3720


 


GAGGGCCTGA CATCAGTCAG GCCCGCCCGC AGTTATCCGG AGGCCTAACC GTCTCCCTGT
3780


 


GATGCTGTGC TTCAGTGGTC ACGCTCCTAG TCCGCCTTCA TGTTCCATCC TGTGCACCTG
3840


 


GCTCTGCCTT CTAGATAGCA GCAGCAAATT AGTGAAAGTA CTGAAAGTCT CTGATAAGCA
3900


 


GAAATAATGG CGTAAGCGGT CTCTCTCTCT CTCTCCTCTC TCTCTGCCTC AGCTGCCAGG
3960


 


AAGGGAAGGG CCCCCTGGCC AGTGGGCACG TGACCCACAT GACCTTACCT ATCACTGGAC
4020


 


ATGGTTCACA CTCCTTACCC TGCCGCTTTG TCTTGTATCC AATAAATAGC GCAACCTGGC
4080


 


ATTCGGGGCC GCTACCAGTC TCCGCGTCTT GGTGGTAGTG GTCCCCCAGG CCCAGCTGTC
4140


 


TTTTTCTTTT ATCTTTGTCT TGTGTCTTTA TTTCTACACT CTCTCATCTC CGCATACGAG
4200


 


GAGAAAACCC ACCAACCCTG TGGGGCTGGT CCCTACACCC TGGCTTTGTA GACTGGAGCC
4260


 


TAGGCACGAC TCAGCTGCTG TAGTGAATTG CGATCCTCCA AACCCAGCAA GGCACCTGCA
4320


 


GGACATCTGG CCCAGTCTCC TCGTTGAGCC AGTTCACGAA AAAGAGACTT TTCTGAGTGA
4380


 


CATGCTAATG GGCAATATGA GGACTAAATG GGATGGTCTC CAACTTGGAC AAACCAACAG
4440


 


TAAAAGCCAC TTTGCGGGGA AAGAAACTTT TCCTTTTTTC TTTTTTTTGA GACAGGATCT
4500


 


CACCCTGTCA CCCAGGCTGC AGTGCAGTGG CATGACCTTG GCTCACTGCA GCCTCAACCT
4560


 


CTCTCAGGCT CAAGCAATCC TCCCGCCTCA ACCTCCCATG CAGCTGGGAC CATAGGTGCA
4620


 


TGCCACCACA CCCAAATAAT TTTTATATTT TTTGTAGAGA CGAGGTTTCA CTATGTTGCT
4680


 


CGGGCTGGTC TCAACTCCTG GGCTCAAGCA ACCCTCCCAC CTCAGCCTCC CAAAGTGCTC
4740


 


AGATTACAGG CAGGAGCCAC CAGGCCTGGC CAACATAGGA AGAAATTTAA ATTTGAATTG
4800


 


AATATTAGAA GAGATGAAAA TTCATCAACA TGGAAAGACA AAGATCATTA ACTAAAGCCA
4860


 


AACCAGAATG GAAGCTGTGT GTACAGTGGG GTCTCATGCT GGGAACGCGA GGGGCACGTG
4920


 


CAGGGCTCCA CGGTGTGGCG ACGCCCCATG CTCCCTTTGT GGGGGTTCAT CCAGCGGAAC
4980


 


ATGAGGACCT GGGGTGCTTT TCAACATGTA CGTGAGTTTA ATAATAAAAA GGTTTAAGGA
5040


 


AAGAAAAATT CATATGTTTC TATATAAACA GAACATCTGG AAAGATCTAT TCTAAGGTGT
5100


 


TGACAGTAGG AATCTCTAGG TAGTAGTAAT ATGGCCTTTT TGAATTTTTG CTTATCAGTA
5160


 


TTTTCTAATT TTCTTTTTCT TTCTAAATAA TTCTAGCTAT GAAATAATTT TCTACCATAT
5220


 


ATATTTTGTA ATAAAAATGG TTATATTTAA TTTTTTAAAG GCTGTACAAA CTTCCTGATA
5280


 


AAATGGCAAA TTAGACACAC ACATGTGGGC CGGGTACAGT GGCTCGCGCC TGTAATTCCA
5340


 


GCACTTTGGG AGGCTGAGGC AGGCAGATCA CCTAAGGTCA GGAGTTTGAG ACCAGCCTGG
5400


 


CCAACATGGT GAAACCCCGT CTCTACTAAA TATACAAAAA TGAGCTGGAT GTGGTGGCAC
5460


 


ACACCTATAG TGCCAGCTAC TTGGGAAGCT GAGGCAGGAA AATTGCTTCA ACCCGGGAGG
5520


 


CAGAGGTTGT AGTGAGCCGA GATCATGCCA CTGCACTCCA GCCTAGGCAA CAAGAGCGAG
5580


 


ACTCCAACTC AAAAAAAAAT AAAAATAACA CACACGTGAA TAGGCTCCTC ATGGAAGTCA
5640


 


TCACAACAAT GCAGAGGGAA GAGCTTCCAA AGTGTAAACC CAGAAGCGAG GAGCAGGAGG
5700


 


GTGCGCGCAG ACGCAGAGAG CAGCAAGGTG CAGACTGAGA GGCGGAGGCT GGCCGTGGGG
5760


 


AGATGACTGA TGCTCAGTTT ATACCCCAAA TCCGTAAATC TAGAGGCCTG GCACATCAAC
5820


 


TACCTCTGCC AGCAGGAATG AGGGAAAGGA GGGCAACCAA AAGATGTCCC ACCCTCACCC
5880


 


ATCCAGCTAC CTGCCATCCT CAGCCCCACT GGCAGAAGAC CCTGAGAGGT GGAGGCAGGC
5940


 


CCCTGCCTAC AGGACCCTGA GAGCTAGGGG AAGGCGTTAT CCTGAACTGT GTCCCCCGTA
6000


 


AAATTCATAT GTTGAAGGCC TCATCCCCAG TGTGACTGTA TTTAAAGATG GGGTCTTCAG
6060


 


GAGATAATTT AAATGAGGTC ATATAAGTTG GCCCTCATCC AGTAAGACTT TGACCTTCTG
6120


 


GTGGTTTTTT TTTTTTTGGA GACTGGGTCT CACTCTATCA CTCAGGTTGG AGTACAGTGG
6180


 


CACGATCACG GCTCACTGCT GTCTCCAACT CCTGGGCTCA GGTGATCCTC CTGCTTCAGC
6240


 


CTCCTGAGTA GCTGGGACTA CAGGTGCTTA CCACCGCACC CAGCTGGTGG TGCATTGTGT
6300


 


TTTTTGTAGA GATGGGGTTT TGCCATGTCG CCCAGGCTGG TCCTGAACTG GGCTCAAGTG
6360


 


ATCTGTCTCC CTCGGCCTCC TGCAGTGCTG GAATTACAGG TATGAGCCAC CGCGCCTGGC
6420


 


CGACCGTGAC CTTCTAAGAA GTGAAAGAGA AAGATCTTTC TCTCTCCCTC CCTCTCCATC
6480


 


ATGAGGACAC AGCAAGAAGT CGGCCATCTG CAAGGTAGAA AGCGAGTCCT CCCAACAGCT
6540


 


GAACCTGGCA GACCCTGATC TTGGACTTCA GCCTTCAGAG CTGTAAGAAA ATAACTCTCT
6600


 


GCTGTTCAGG CCACGCGGTC TACGGCAGCC CGAGCAGACT AAGACACACG CCATCTGGGG
6660


 


AGTCAGACCA GATCAGGAAG AAAGGCCTAG AGCTCAGGAT ACTGAAGGTC CCAACCCGGT
6720


 


GCTGGACCAG ACCACCCCGG CAGCCGCGGC CACGGAGTCA CGGCTCGGGT GAGGTGACCT
6780


 


GGACACCATC CCGGCAGCCG CGGCCACGGA GTCACGGCTC GGGTGAGGTG ACCTGGACAC
6840


 


CATCCCGGCA GCCGCGGCCA CGGTGTCACG GCTCGGATGA GATGACTCGG ACACCACCCC
6900


 


GGCAGCCGCG GCCACGGTGT CAGGGCTCAG GTGAGGAGAG TTGGATATGG GACTGGGCCT
6960


 


ACCCCGAGGC TGCTTCCACC CAGACGCCTG GGTGGGTGAC ACGAAAGCTG GGCTCAGTTG
7020


 


GGATCAGAGC AGCCTCTCCC CAGGTCAGAA ATGACCCTGG GCTCCTCACA GTAGCCCTAG
7080


 


GGCACCATGA GAAAGCTACG TGGACTTCTC TGACCAAGGG TCACTGCTGC CACACTACTC
7140


 


ATTGCAGGCC ATGTCAGGGC TCAGCTGAGG AGACGTGGAC ACCACCCCAG CAGCCGCGGC
7200


 


CACGGCGTCC CAAGGGAGGG ACTTGGGCAC TGCCTCTCTG GGCAAGAGTG GGGAGGTGTG
7260


 


GGGTGGGAGA TGTCTGGAAA CATCATGGAC ACATGCCGGG AAAACACGGA AGCTGTGCAC
7320


 


CAAGGTGCTG ACAAAGGAAA AAGGAGAATG GAGGTGTGAA CATCCAGCTA GCAGGTCCCA
7380


 


CTCAGAAACT CCTGCATTTC CAGACATGGC CACCAGCTCT GTGGATGAGA CAGGGGAGGA
7440


 


CAGGGTACCT CACACCAGGA ACCCACACAG GTCCATGTCT TGCTCTGTGA TCACACAACA
7500


 


GCCTCCACCA CCCTGACATG CAGGAGGGAG GTCAAAGCCT CGGGTCCAAC AACAGGCTCC
7560


 


ACAGCAAGGG AAGAAAGGCA GGAAGGAACT CAGGGCCAGG TCCTCCCAGG CAGCAGCTGC
7620


 


CTGCACGCTG TCCACCAAGG GAGGTCTGAC CTACACCGCA CAGGGGTTGG CAGTCTAGAG
7680


 


TCGTCCTCTG TCAAACGGTG AGAAAGTCAA AAGCTCATGC TCAGTGATAT GCTAGGTCAG
7740


 


CATGAAGATG CCACACATGA GACACAGCAA GGATGAGACC AACGGGAAGA CTGCCCCAGA
7800


 


CCAGAGCCCC AGAGCCCTCT GGGGAGGAAG AATAAGGATG GCAGCCTGGG ACTGCCCGGG
7860


 


GCTGACTCTG CCTTTATTTC ACCCCAGCAG AGGCAGGAGT GACACCGGCT CACACCAGGA
7920


 


GCAGCTCTGC CACCTCCTAG CAGTTCCACC TACGGGCAGC AAAACAAAGC TGGCAGTTTG
7980


 


GGCAAATGTT AGCGTTTTTG CCAACTAACA TTTGAATCGG ACATCTGGTA CAGAGATGAG
8040


 


GAAGAAAACA CTCACAGTTT CATGAAGACT GTCAAGAAAA TCACTGACTC TTCACTTCAT
8100


 


TTATGAAAGG CCAGCTCTCT GACATCCCTA CCACTCCCTC TCACATGAGA AATCACGGCC
8160


 


TTTCAGGACG TGGAGCCACG TGGCCATGCA GGTACGGGAG GCCTCCCCGC AGCTGCAGCT
8220


 


GGGTCTTCTG GTCCCCGTGC CATTTCTGCT TTTCTTCGCT CTCTACTTAC ACACACATTT
8280


 


GAGTCCAGTC TCAGAAGAAC TGGAACTAGA AAAATCCTGA CACTTGTCCC TTACTACGTT
8340


 


AATGCCAGCT GTGCCAAGGA CAGCCCAACC CAAGCCCCCA TCAGCCCCAA TGGCACCGAG
8400


 


GCCCGAGCTT ACCCGTGAGG GGCCAAGTTG GTCGTCACCA ACACGGTCTT CACCCCCTCC
8460


 


ACACCACTGC CGTCCACTGC AGTGTCCGGA GTTGTCACAA CCACCACCTC CTCCATGTGC
8520


 


ACACTCACGT CGGGAGTCGC CATGGCTCAG CGGAAGGGGA CGCCCAGGCC AGCAGCGTCA
8580


 


GTCCTCCAGG GTCCCAAGTC CTGGAGGAAG CAAGGCAGGG CACAGGGATG GAGTCATCTC
8640


 


CACATCCACA CAACATAGCA CTCACAAAGG CATCTCTAAT CAGCTCCAAA GACCCACCCT
8700


 


TGAGTCCCAG ACTGCTACCT CCTGACAAAA ACGAGCGGCA ACAGAAGGGC TACTCCAGGC
8760


 


TCTGGTTCCG AGGGCGGTGT AAGCGCACTC CACCCGTTTT TCCCACTGGA TAAGCCGAAA
8820


 


CCCTTGGGTA GAAAGCACAG AGCCACTCCC TCCACGTGGG GCTCAGAGCA GGAGGACAGG
8880


 


AGGGGCCTGG AATTCCAAGC AACTTCCCTG GACGCAGGCT CCCGGCTTGC CAGTTCTTCC
8940


 


GTCTCTCCTG GCCTGAACTC AAAGCCAGCC CCAATCCCTG AACTGAGTTT CAGGTGCAGA
9000


 


AAGCACTCCA AGAAGTCCTC GCTGGTCTGT GGAACGGGAA GGGAAACCCA TTCAAGACAG
9060


 


AAAGAGAGGA GGGAAACGCC CTGGGTTTTT TTGGGTTTTT GGGTTTTTTT TGAGACGGAG
9120


 


TCTCGCTCTG TCGCCCAGGC TGGAATGCAG TGGCACGACC TCGGCTCACT GCAAGCTCCA
9180


 


CCTCCTGGGT TCAAGTGATT CTCCTGCCTC AGCCTCTCCA ATTGCTGGGA TTACAGGTTT
9240


 


CACCATGTTG CCCAGGCTGG TCTCAAACTC CTGACCTCAG GTGATCCACT CACCTCGGCC
9300


 


TCCCAAAGTG CTGGGATTGC AGGTGTGAGG CACCATGCCT GGCCTGCCCC GGGTTTAAAA
9360


 


ATTATTATTA TTTTGTCTTT CCTGGCTTTG CCTTCAGCAA GTCCAACCCC TGCTAAAACC
9420


 


CGGTGATAAT GGCTGTCCTG GCCCAAAAAG CTTGGAGACA GGGGAATCTT CCTCCTGACT
9480


 


AAAGGAATGG TGCCCCAAGA GTGTGGGGGC TCCCTGTTGC CCTCTCACTC TCCATCCCCT
9540


 


ACCTAGCACA GCGAACACAA AAGCCCCTGG TTTCCAGCCA GAGGGCAACG AGCCTGGAGT
9600


 


CAGAGTGTGG GGGAGGCGAC AAGAGGAGAG GGGAGAAGAG AGGATGGCAC ACAGCTGTGT
9660


 


GTGAGCGCCT GGGTCGTCCC AAGACAGTCT CTACGTGGTC CTGACCCTAA AGGGCAAAGG
9720


 


GAAGAAAACT GACCTACAGG ATAGGCCACT GCCCAGGTCT CAGATGGGCC CCAGTGGCGC
9780


 


ATATGGGACA GATCCACAGT GCACTGGAAA GTCTCTAAAA TAAACTGGCC TAAGAACACA
9840


 


GACACAGGAA CGGGGTGCAA AATTTGCAGC CTGAACCTAA CCAGCTCGAT TTCTTGCTAT
9900


 


GAAAAAAAAA AGTCTACATT CTCTGTGAAA CTTAAAACAA GACCTAGAGT CCATAGCACA
9960


 


GTAGTCAAAG CATCCAGAAC ACGATCAAAC TTCCTGGCAA AGGGTAGTCT GGTTGATTCT
10020


 


CAAAGGAACA AATACACAAG AGAAGCTGGC TCTTGAACGC AGAATCCAGA GACTTTCAGG
10080


 


TGCTATCGGA CCAGCTCCAA GAGGAAAGCA AACATTGTCA ACCAAGTGGA AAGAAAATCT
10140


 


TGGTATAGAA ACAGGAGTTA TAACCAAACA GAAATGTGAA AATTAAAAAC GACAACCAAA
10200


 


AGAAAATACA CAAAGCTGGG ATAGTCTCAG CTACTCGGAA GGCGGGGCTG GAGGATCGTT
10260


 


TGAGCCTAGG AGATTGAGGC TGCAATGAGC TGTGATCACA CCACCGCACT CCAGTCTGGG
10320


 


CAACAGAGTG AGAACTCTCT CAAAAAACGA AAAAGAAAGA AAGTAGAACA GAAGTGACCA
10380


 


GGGGCTGGGG GAGGGAGTAC AGGGAGTTGT TCTTTAATGA GTACAGAATT TCTGTTTGGG
10440


 


ATGATGAAAA GCTCTGGAAA TGGACGGCGG TGATGGCTGC ACAATCACTG TGGCTGTTCT
10500


 


GAATGGTGCT GAACCACACA TTTAAAAACA GTTAAAATGG GCTGGGCGTG GTGGCTCACG
10560


 


CCTGTAATCC CAGCACTTTG GGAGGCGGAT CGCCTGAGGT CAGGAGTTCG AGACCATCCT
10620


 


GGCCAACACA GTGAAATCCT GTCTTGACTA AAAATACTAA AAATTAGCCA GGCATGGTGG
10680


 


CAGGCACCTG TAGTCCCAGC TACTTGGGAG GCTGGGGCAG GAGACCTGCT TGAACCCAGG
10740


 


AGGCAGAGGT TGCAGTGAGC CGAGATCGTG CCACTGCACT CCAGCCTGGG CAACAAGAGC
10800


 


GAAACTCCAT CTCAAAAAAA AAAAAAAAAA AAAAAAAAAA AAGTTTAAAA TGGTTAAATT
10860


 


TTATGTTATG TATATTTTAC CGTAATAAAA ACACTGTAAT GCTACTATAA TAGAATGACT
10920


 


CATTAGGATT AGATATAGAC TAGAAAGTAC AGAATATAAA AACTTTTTAA ACAAAGAAAA
10980


 


ATTTTCATGG CCAGGCATGG TGTCACACCT GTAATCCCAG GACTTTGGGA GGCCAAGGCA
11040


 


AGAGGAATGC TTGAGCTCAG GGGTTTGAGA CCAGCCTGGG CAACACAGCA ACACCCCATC
11100


 


TCTGCTAAAT AAATAATAAA AAATAGCCAG GCATGGTGGT GTGCACGCCT GTAGTTGCAG
11160


 


CTACTCTGGA GGCTGAGGCA GGAGGATCAC TTAAGCCCAG GAGGTCAAGG CTGCAGTGAG
11220


 


CCATGGTTGT GCCACTGCGC TCCAGCCTGG GCAACAGATC AAGACCTTGT CACAAAAAAA
11280


 


AGAAAGAAAG AAAAGAAAAA AGAAAGAAAA TAAAATCTTC CAGAACTTTT AAAATCATCA
11340


 


TTGTTAATAT AAAAATAACA TCACCTGCCC CTAGGACTGT AACAAACAAG TGTGTCTAAG
11400


 


GACAGGAGTG GGTCCACCCC AACCTGGCAC GCAGTGGTCC CCTGCGGAGA GTCTGGCCCT
11460


 


GCACTCACTA AGAGGAGGCA CTCATAGCCC AGCCAGGCCT CTGCAATTAT GCCTTCAATG
11520


 


CCAGAACTAA CTCACCCAAA CTGAACAATC GATCACAAAA TGTGCCTTCA GGTCTCAAGG
11580


 


TTCTTGCTAA ATCTTACTCA ACCGACATTT TCCAGCATGG GAACATTTTT CTGAATGTCT
11640


 


TAGGGAGAGG AAGTCCGCAA GAGAACAAAA GGTCCTCAGG CCACCCTAGC TTCTTTTCCT
11700


 


CCATTCCACA GGCTGTCTTT TGTCTGGGTA TGCACTGGAC CAGGGGGCTC TACTTCTTCC
11760


 


TACCTGGGCA TGGGTCTCCA CACAACTCCA AGGTAAAGGG CCACAGGCAA GATAAAGGGG
11820


 


AGAAAAGAAA GCTACGATTT CCTGGGCCAC CAATCGCAAA TGGCAGCCAG TCTCTGAAGT
11880


 


AACCCTTGAC CAGAGATCCA AGGAACCAAG AAATGTAGGT GATCTGAACA GAGGGGATGG
11940


 


TGGTTAAACA CCATGAAGGA AAGACCCATT CTCAAAGAAA AGGAAGCAAA AAGAAACCGT
12000


 


GGGGAGCTGG GTACCACCCG CAGCAAAGAC CCCGCACGCG TTACTGACGC CAGCCTGGCC
12060


 


TGGGAGAGCA GTGAGTGTGG CGGACGGTGA GTGGCGGGGA GGGCTGTGGT AGGTTTAGGG
12120


 


TAAGAAGGGG CAGCGCCCAG AGCCCAGAGA ACACCAGTGA GGGCTCCACA GGAACACTAC
12180


 


TCAAAGTATT CACGGAACAC ATCTAAACAC AAGCACTAAG GACTAAGTGC GAGGGACAAG
12240


 


AAAATATTCC CCGTTTCCTG TTTCAGGAGG GTATCGAAAA TGAGTGATGG AAGGAAAATG
12300


 


TATTGTTTAA ATGAGGAAAA AAAATTTTTA CAAATTAAGA ACATCCTGGA ACATGATGAG
12360


 


CCGTTTACTG TCACTCAATT TAAATGGTGG CCATCTAGGA CAGAGCGCCT AAGGGGAAAG
12420


 


GGGGCTCACA GGTGAACCCC TCCAGCTGCT GGTGGGCAAT TTCCCATTAG GGCATCAGGG
12480


 


TCTCTGAAGA CTGTCTTCAG ATGCTTTTTA GCCAGGAAAG TTACAATGAT GAATTCGTTT
12540


 


ACACTGGCGG AATTACTTCG TATTTCTCAA ATATAATGTT TTCACTAGCA TAACTTTGTT
12600


 


GTTGTAGACT TAGGCTTCAA AATAAAGAAC TTTAAACAAA CATGAATAAA AAGCCACTTT
12660


 


AGGCCGGGCG CGGTGGCTCA CACTTGTAAT CCCAGCACTT TGGGAGGCCG CGGCGGGTGG
12720


 


ATCATAAGGT CAGAAGTTCA AAGACCAGCC TGATCAATAC GGTGAAACCC CGTCTCTACT
12780


 


AAAAATACAA AAATTAGCCG GGCGCGGTGG CAGGTGCCTG TAATCTCAGC TACTTGGGAG
12840


 


GCTGAGGCAG GAGAATCGCT TGAACCTGGG CAGCAGAGGT TGCAGTGAGC CAAGATCATG
12900


 


CCACTGCACT CAAGCCTGGG TGACAGAGTG AGACTCTCTC TTAAAAAAAA AAAGCCACTT
12960


 


TAAAATTTTA CTCAGGCCAG GTGTGGTGGC TCACGCCCAT AATCCTAGCA CTTTGGGAGG
13020


 


CCGAGGCGAG CAGATCACCT GAGGTCAGGA GTTAGACCAC CCTGGCCAAC ATGGTAAAAC
13080


 


CTTGTCTCTA CTGAAAACAC AAAAATTAGC TGGGCGTGGT GGTGTGCCCA TGTAATCCCA
13140


 


GCTACTCAGG AGGCTGAAGT GAGAGAACTG CTTGAACCCG GGAGGCAGAG GCTGCAGTGT
13200


 


GCCAAGACTG CACCACTACA CTTCAGCCTG GGCGACAGAG CAAGACCCTG TCTCAGAAAA
13260


 


AAAAAAAATT CAAAAATTTG GCCAGGCGTG GTGGCTCACG CCTGTAATCC CATCACTTTG
13320


 


GAAGGCCGAG GCGGGTGGAT CACCTGAGGT CAGGAATTCA AGACCAGCCT GGCCACCATG
13380


 


ATGAAACCCT GTCTCTACTA AAAATACAAA AAAAAAAAAA CAAATTGGCC GGGCATGGTG
13440


 


GCGGGTGCCT GTAATCCCAC CTACTTGGGA GGCTGAGGCA GGAGAATCTC TCGAACTCCG
13500


 


GAGGCAGAGG TTGCAGCGAG CCAAGATTGT GCCACTGCAC TCCAGCCTAG ACAACAGAGC
13560


 


GAGACTCTGT CTCAAAAAAA AAAAAATTAA AATTAAAAAA TAAAAATTTC ATTTAAAATA
13620


 


CTACTGATCT CCCGTGCTGA CTTCTCGGGG TTTAACTCTC ACTGAGGAGA CGCTGCTTTC
13680


 


ATAAGGGTAA GCTCAGCAGG GGCAACTAAA GTCATTTAAG CAGAGAGCTG CAAAGAGGCA
13740


 


ACAGCCTCAC TGCAGGCAGG GGTCCTCGTC ACAGCTTCAG GGCTTTGCAG AGGATTACGC
13800


 


AATGTACACG CACAAAACTG AATTCCAGCC TCTCCATTGG CAACTGCATA CATACATATA
13860


 


TTCTTTTTTT GAGACGGAGT CTCGCTCTGT AGCCCAGGTT GGACTGCAGT GGCCCGATCT
13920


 


CGGCTCAATG CAAGCTCTGC CTCCCGGGTT CAAGCGATTC TCTTGCCTCA GCCTCCTGAG
13980


 


TAGCTGGGAT TACAGGCGCC CACCACCACG CCCGGCTAAT TTTTGTATTT TTAGTAGAGA
14040


 


CGGGGTTTCA CCATGTTGGC CAGGACAGTC TCGATCTCCT GACCTCGTGA TCCGCCCGCC
14100


 


TCTGCCTCCC AAAGTGCTGG GATTACAGGC GTGAGCCACT GAGCCTGGCC TCCAATGGCA
14160


 


ACTATATTAA AGGTTCAAAG CAATATGCAC AAAAGTTACC TCACAGAAAA TAGTGCAAGT
14220


 


CCTTGATACA ATGCTCTTTA GACACAGAAG AAGCACTATA GAATAGAGCA CCTCGCCCTA
14280


 


TTGCCTTCCC AAGGGCGAGC ACCCCCTCCT CTCTCCACAG CTCCTTCTTT GTTTTTTTGA
14340


 


GATGGAGTCT CGCTCTGTCA CCCAGGCTGG AGTGCAATGG CAAAATCTTG GCTCACTCCA
14400


 


ACCTCCGCCT CCCGGGTTGA AGTGATTCTC CTGCCTCAGC CTCCCGAGTA GCTGGGACTA
14460


 


CAGGCACCCA ACACGCCTAG CTAATTTTTG CATTTTTGGT AGAGACGGGG TTTCATCATG
14520


 


TTGGCCAGGC TGGTCTCGAA CTCCTGACCT CCAGTGATCC TCCCACCTTG ACCTCCCATA
14580


 


GTGCTGGGAT TATAGGTGTG AGCCACTACA CCTGGCCTCT CCACAGCCCC TTCTGTGTTG
14640


 


AAGCCAAGAC CCACCCAGCT TTGATCCCAA GGCTTGGGTT CCCCACTACT GTGAAGTGAG
14700


 


TTTCCAAATT ATTAGGTAAA TCAGATATGA GAAAATATTT TATTTTACTT TTTTTTTTTT
14760


 


GAGACGCAAT CTTGCTCCCT CACCCAGGCT GGAGTGCAAT GGCACCATCT CCACTCACTG
14820


 


CAACCTCTGC CTTCTGGGTT CAAGCAATTC TCCTGCCTCA GCCTCCCAAC TAGCTGGGAT
14880


 


TACAAGTGCA CACCACCACG CCCGGCTAAC TTTTGTATTT TTAGTAGAGA CAGGGTTTCA
14940


 


CCGTGTTAGC CAGGCTGCTC TCAAACTCCT GACCTCATGA TCCGCCCACG TCGGGCTCCC
15000


 


AAAGTGGTGG GATTACAGGT GTGAGCCATC ACACCTGGCC CAAGAAAATA TTTTTAAACT
15060


 


AGTATTCTTC ACCGGCACGG TCAACACTGA TGTAATTGAA ACTGTTGTAT TTGAAGTGTT
15120


 


AGCAAAGAAA GAGAATTCTG GTTCAACAGA AAAGTCAGTC ACGACTTTTC AGTCACGCAT
15180


 


GAATTACACA GTAACCAAAT AGATAACATG CCATCACTGA CGACGGGCCC ACAACAAATC
15240


 


AGCTCCGACC AACAGGGTCC ACACCACCAT GGGTCTACAC AGATCCAGGT CCCGCCTGTG
15300


 


AGCCTACAGT GACGCGGGCC CCTGTGGGGT GGTCCCTGCA GGTCAGGTCC CTGAGAGTGG
15360


 


GTCCCAGTGG GGTGATCCCT GCGGGTCGCG TCCCTGCGAG TTGGGTGCCT GCCGGGTGGC
15420


 


CCCTGCGGGT CGGGTGCCTG CGGGGTGGTC CCTATGGGTC GCGTCCCTGC GGGTCGGGTG
15480


 


CCTGCGGGGT GGCCCCTGGG AATCGCGTCC CTGCGGGTCG GGTGCCTGCG GGGTGGCCCC
15540


 


TGGGGATCGC GTCCCTGCGG GTCGGGTGCC TGCGGGGTGG CCCCTGGGGA TCGCGTCCCT
15600


 


GCGGGTCGGG TGCCTGCGCG GTGGTCCTTG TGGGTCGCGT CCCTGTGGGG TGGTCCCTGT
15660


 


GGGTCGCGTC CCTGTGGGGT GGCCCCTGCG GGTCGCGTGG TGGCCCCTGC GGGTCGGGTG
15720


 


CCTGCGGGGT GGTCCCTGTG GGTCGCGTCC CTGCGGGTCG GGTGCCTGCG GGGTGGTCCC
15780


 


TGCGGGTCGC ACCCCTGCGG CGTGGTCCCC CCGGGATGGG TCCACCGAGG AGGCCGCTGG
15840


 


AGGCCGAGCC CGCGCCCGCC CGCGGCGCCA AGATGGAGGC AGGAAGCGCC GCCGCCCGCG
15900


 


CCCGCCACCG CCCGCGCCGC CCGCCTGACG CCGCCGTTGC GCCTGACGCC GCCGCCCGCG
15960


 


CCGCCGCCCC TCCCCCGGCC CTCCCCTCCC CCCGCCGTAA CGTCCTGACG CTCCGCAGGG
16020


 


ACCCCTGACT GGACGGCGGC GCGTGAGCGC AGCGAGAGGC CTCGCCGCGG GGGGGCCGCG
16080


 


GGCTCGCCGG CGCCGCTTAC CTGGGGCCGC GCCGGGCCTG CTTAGGCACC CGGCGGGGGC
16140


 


GGCGGCGTCG GGAGCTGCGG CGGCGGCGGG CGGCGGCGGC GGCCGCGGGC TTCGCTCCTT
16200


 


GTTGGGGATT CCGCGGCGGC GGCGGCGCGG GCGCGCGCTT CCTAGTGACG CAGGCGGCGG
16260


 


GGCCGCGCAC GCACGGGGCT GGGAGGGCCG GACACTTATT TGGCGCTCGC GGAGGAGGAA
16320


 


GGCGGGGCCG TGAAATAAGG CCCGACGGGC CCCGGGGCGC GTGCGCGGAC CGACACTGTC
16380


 


AGCTCCTAAC GCCGCAGGTT CCTCCTGGTC CCCGAGGCCC CCGGTCGGGC GTTGCCTGCC
16440


 


CCGCGCGGGC GGCCGGGCCG AGGGACGATG GTCAGTGGAC GGACGGCGCC AGGGAGCAGT
16500


 


GCCCACGCGC GGCAGGGCGG TACCTTCAGG CCTCCAGGTA CGGGCGCTCC TCGCCCGGAC
16560


 


GCTGCTGTGT GTGAATGGGC GCGAGGGGAC TCCCCTGCGG GGCGGACGCC TGAACACGAG
16620


 


GCTGTGGAGG AGGACGCTGT AGGGTGCGCG GACTCACGCG GAACATGCCA GAGGCTCAGC
16680


 


CAGCCACGGC GCTCCCAGCG TGGAGGGCGA GGGGCATCCG GGAGCGGCCG GGAGGGCTCG
16740


 


GTCACCCCTC AAGCTGTCAC CCCAGTCCCA CAACCAGCAC CCCGATCCTA TCGCAGTCCC
16800


 


ACAGCCGACA CCCCGATCCC ACCCCTGCCC AACAGCCGGC ACCCACCCCA ATCCCATAGC
16860


 


TAACACCCCG GTCCCACCGC TGTCCCACGG CCGGCACCCC GATCCCACCC CAGTCCCGCA
16920


 


GCTGGCACCC CGATCCCACC CCAGCCCAAC AGCTGGCACC CACCCCGATC CCACCGCTGT
16980


 


CCCACAGCCG GCACCCCGAT CCCACCCCAG TCCCGCAGCC GGCACCCCGA TCCCACAGCC
17040


 


GGCACTCACC CCGATCGCAT AGCATAGCTG ATACCCCGAT CCCACCCCAG TCCCATAGCC
17100


 


AGCACCCCGA TCCCACCCCA GTCCCATAGC CAGCACCTCG ATCCCATAGA TGACACCCCG
17160


 


ATCACGCCCC AGTCCTATAG CCCGCACCCC GATCCCACCC GAGTCCCGCA GCCGGCACCC
17220


 


CATCCCACCC ATGTCCCACA GTCGGCACCC CGATCCCACT CGGATCCGGC AGCCAGCTTG
17280


 


GATCCTGTGG CCCTCCTCCA GCCCCCAGGG CTCATTTATA TGTTTTATTG GCAGAGGCTG
17340


 


GGGCTGGCTC TGTTGGCCTC TGTGCTGGGT TTCTTCCTCT GCACCGCAGG ACTGGCTCTC
17400


 


CTGACCTCTC CAGGTGTCAT CGAACACCCT TGTGCTTGCT GTCACCCGCT GCCTGTCTGC
17460


 


AGGATCCCGG ATTCCGTATC AGGGGACCGA AATTAGTCGG AAAATAGGAA GCAGGTGCTC
17520


 


GCTTGGATGG AACCCTGACC CTGTGCTCAC ACTTGTAGGA GGAGGGCTCT GCAGGCCGCC
17580


 


TCCCGGAACG GGAGGTTCCC AAGCCACTGC ACTTCGGAGG GGCTGTAATT AGAGTTGCAC
17640


 


ATTCATTCAG TTCCCAGTAA AGTAGAACGT GCTCCAGCCA GTGAGGAAAA GGTGTTTTTA
17700


 


AAAATTAGAT TGGCCGAGTG CGGTGGCTCA TGCCTTTTAC CTCAACACTT TGGGAGACAA
17760


 


AGGTGGGAGG ATCACCTGTG GCCAGGAGTT CAAGACCAGC CTGGGCAACA GAGCCTGTCT
17820


 


CTGGGGAAGA ATAAAAAAAA AAATTGAGCC TTTGTCAGTG CTACTATTTT ATTATCTGGT
17880


 


AAATATGAGA GGGTTCACGC GGTCTATGTG TGTCATTTAT CTGAGTTTGC CTATCGTCAC
17940


 


GTTTTGGAAA TAAATGTCAA TAAAGTCGAA GAGGAGTGCT GAGGGGGGCC TGGGGATGGG
18000


 


AGGGTGGCTA CATCATGCCT GTGTGTTGCG CAAGCCCACC GAGGTCGGCC TGGCGTGAGC
18060


 


CCTGGGGCCT GTTCTGCCTC CTTCACTCTG GGGCTCCAAG AGACAAACTG GGCAACAAGA
18120


 


GAGAAACTCC ATCTAAAAAA AAAGAAAAAT CACCTCCAAG ATAACTTAGC TTTCTTCTGC
18180


 


TGGCATAACA AATTATCTCA AACTTAGTCG CTTAAAAATG CAAATTTAGG CTGAGTGCGG
18240


 


AGGCTCACGC CCATAATCCT AGCACTTTGG GAGGCCAAGG CAGGATTGCT TGAGGCCAGG
18300


 


AGTTCGAGAC CAACATGGCC AGAACTGTCT CTTTTTAAAA AATGCAAATG TGTCCGGCAC
18360


 


GGTGGCTCAC GCCTATAATC CCAGCACTTT GTGAGGCCAA GGCGGGCAGA TCACGAGGTC
18420


 


AGGAGATAGA GACCATCCTG GCTAACACTG TGAAACCCCC TCTCTACTAA AAATACAAAA
18480


 


AATTAGCCTG GCGTGGTGGC AGGCGCCTGT AGTCCCAGCT ACTCGGGAGG CTGAGGCAGG
18540


 


AGAATGGCGT GAACCCAGGA AGCGGAGCTT GCAGTGAGCC GAGATGGCGC CACTGCACTC
18600


 


CAGCCTAGGC AACAGAGCAA GACTCCGTCT CAAAAAATAA ATAAATAAAA CTGCAAATGT
18660


 


ATTCTCTAAC TGTTCTGTAG GTCGGAAGTC CAGCCCAGCC TCACTCCGCC AAAATCAGGG
18720


 


TGTCTGCAGG GCCGATTGCT TTTGGAGCTC CAGGGGAGAA GCTGTTCTGG CCTTTCCAGT
18780


 


TTCTGGAAGC ACTTGAGCCC CTTGTCTCGT GGCCTATCCC ACACCTGAAA GCCAGCCAAA
18840


 


GCCAGTTGAG TCCTCACCCT GTTGGCCCCG ACACTGATCT CCTGCCTCCC TCATCTGCTG
18900


 


TCAAGGCCCC TTGTGATGAC ATGGGGCCAC CAGCTGGCCC AGGGCACCTC CTGTCAGAGT
18960


 


CCGCCGACCA GTGACCTTCA TTCCATCTGT CGCTGTAATT CCCCTTTGCT TGGAACCAAC
19020


 


GTTCACAGAT CCCAGGGGTT AGGATGTGAA TATCTTGGGC AGGGCTGTGG GGGGGCTATT
19080


 


CTTCCTTCTA AAATATTTAT CATTTTTGTT TTGGGGATTT TTTTGGTTTG GTTTTTTTTG
19140


 


AGACAGAGTC TCGCTCTGTC GCCCAGGTTG GAGTGCAATG GTGCAATCTC AGCTCACTGC
19200


 


AACCTCTGCC TCCGGGCAGA CGTGAGCCAC TGCACCAGGC CTGTTTTTGT TTTTGTTTGT
19260


 


TTTGTTTTGT TTTTGAGATG GAGTCTCGGC CGGGCGCGGT GGCTCACGCC TGTAATCCCA
19320


 


GCACTTTGGG AGGCCGAGGC GGGCGGATCA CGAGGTCAGG AGATCGAGAC CATCCTGGCT
19380


 


AACACGGTGA AACCCCGTCT CTACTAAAAA TACAAAAAAT TAGCCGGGCG TGGTAGCGGG
19440


 


CGCCTGTAGT CCCAGCTACT CGGGAGGCTG AGGCAGGAGA ATGGCGTGAA CCCGGGAGGC
19500


 


GGAGCTTGCA GTGAGCCGAG ATCGCGCCAC TGCACTCCAG CCTGGGCGAC AGAGCGAGAC
19560


 


TCCGTCTCAA AAAAAAAAAA AAAAAAAAAA AAAAAAAGAG ATGGAGTCTC ACTTTGTCAC
19620


 


CCAGGCTGGA GTGTAGTGGC GGGATTATAG GTACGCGCCA TCATGCCCAG TTACTTTTTG
19680


 


TATTTTTAGT AGAGACAGGG TTTTACCATG TTGGTCAGAC TGGTCTCAAA CTCCTGATCT
19740


 


CAGGTAATCC ACCCGCCTCA GCCTCCCAAA GTGCTGGGAT TACAGACGTG AGCCACCGTG
19800


 


TCTGGCCATA TTTATTAACT ACAAAGGGAA AGATGATAAT TTTTTTTTTT GAGATGGAGT
19860


 


CTCACTCTGT CACCCAGGCT GGAGTACAAT AGCGTGATCT TGGCTCACTG AAACCTCTGC
19920


 


CTCCCAGGTT CAAGCGATTC TCCTGCCTCA GCCTCCCAAC TAGCTGGGAT TACAGGCGCA
19980


 


CGCTACCAAG CCCAGCTAAT TTTTGTATTT TTAGTAGAAA CGGAGTTTCA CCATGTTGGT
20040


 


GAGGCTGGTC TCGAACTCCT GACCTTGTGA TCTGCCCACC TCGGCCTCCC AAAGTGCTGG
20100


 


GATTATAGGC ATGAGCCACT GCAACCGGCT GAAAGATGGT AATTTTAAAG TAGAGAAACT
20160


 


GGGTTGGCTG GGCATGGTGG CTTATGCCTG TAAGCTCAGC ACTTTGGAAG TCCAAGGCAA
20220


 


GAGGATCGCT TGAGTCCAGG AGTTTGAGAC CAGCCTGGAC AATATAGCAA GACCCCATCT
20280


 


CCGCAAAAGC TAAAAAGTTA GCCAGGTGTG GCGGCACATG CCTGTAGTCC CAGCTACTCA
20340


 


GGAGGCTGAC GTGGGAGGAT CACTTGAGAC CAGGAGGTCA AGGCTGAAGT GAGCTGTTAT
20400


 


TGTGCCACTG CACTCAGCCT GGGCAACAGA GCGAGAGTCT GTCTCCAAAG GTAAAAAAAG
20460


 


GTCCAGGCAC AGTGGCTCAC ACCTGTAATC TCAGCACTTT GGGAGGCCGA GGCGGGCAGA
20520


 


TTCGTTGAGG TCAGGAGTTC AAAACGAGCC TGGCTAAATG GTGAAACCCC GTCTCTACTA
20580


 


AAAATACAAA AAAATTAGCC AGGCATGGTG ACGGGCGCCT GTAATCTCAG CTACTTGGGA
20640


 


GACTGAGGCA GGAGAATCAT GTAAACCCAG GAGGCTGAGG TTGCAGCGAG CCAAGATCAT
20700


 


GCCACTGCAC TTCAGCCTGG GCGACAGAGC AAGACTGTCT CAAAACAAAA CAAAAGAATC
20760


 


TTGAGTCCTG AGTTCCTCTA AGGGAAATTC CAGGCACCTC GCCACCCTTG ACAGGCAAAG
20820


 


GAACAATCTG ATGAGGAAGA AGATAGAAAC AGCTTAAACA ATAGTCTCCC GGCCGGGGGC
20880


 


AGTGGCTCAC GCCTGTAATC TGAGCACTTT GGGAGGCCGA GGCGGGTGGA TCACAAGGTC
20940


 


AAGAGATCAA GACCATCCTG GCTAACATGG TGAAACCCCG TCTCTACTAA AAATACAAAA
21000


 


AATTAGCCGG GCGTGGTGGT GGGTGCCTGT AGTCCCAGCT ACTCGGGAGG CTGAGGCAGG
21060


 


AGAATGGCGT GAACCCAGGA GGCGGAGCTT TCAGTGAGCT GAGATCGCGC CTCTGCACTC
21120


 


CAGCCTGGGC GACAGAGCCT CGAGACTCCA TCTCAAAAAA AAAAAAAAAT TAGCTGGGTG
21180


 


TGGTGGCTCA CACCTGTAAT CCCAGCTACG TGGCAGGCTG AGGCAGGAGA ATCGCTTGAA
21240


 


CCTGGGAGGC GGAGGTTGTA GGGAGCTGAG ATCGCACCAC TGCACTCCAG CCTGGGCAAC
21300


 


AGAGCGAGAC TCTGTCTCAA AAAAAAAAAA AAAAAACAAA AAAACAATAG TCTCCCAAGT
21360


 


AAGTCAGAGT CACAAGGTGT TTTGATTCCC TGTGGAAACT AAAATATAAC AGCTTAACAT
21420


 


ATGTTCTTGA GTTATTTTTC AGAAACTTGG ACATCCACCA GGTGGAAAAT GCTGAGCTAG
21480


 


GAACAGTGGC TATAATTTCA GCCTTTTGAG AGGCCAAGGT GGAAGGATCA CTTGAGGCCA
21540


 


GGAGTTAGAG ACCAGCCTGG CCAACATGGT GAAACCCCGT CTCTAGTAAA AATACAAATA
21600


 


TTAGCTGGGC ATGGTGGTGC AACCTGAAAT CCCAGCTACT TGGGAGACCT AGCTGGGAGG
21660


 


ATCGCTTGAA CCTGGTAGGA GGAGTTTGCA GTGAGCTGAA ATTGTGCCAC TGCACTCTAG
21720


 


CCTGGGCAAC AGAGTGAGAC TCTGTCTCAA AAAATAAATA AATAAAAAGA GAAAAAAGTG
21780


 


TTGCCTGCAG GCCGGGCACA GTGGCTCACG CCTGTAATCC CAACACTTTG GGAGGCCGAG
21840


 


ATGGGCAGAT CACCTGAGGT CAGGAGTGCA AGAACAGCCT GGCCAACATG GTGAAACCCC
21900


 


ATCTCTACTA AAAATACAAA AGTTAGCTGG GTGTGTACAT GTAGTCTCAG CTACTTGGGA
21960


 


AGCTGACCCA GGAGAATCTC TTCAACCGGG GAGGTGGAGG TTGCGATGAG CTGAGATCAC
22020


 


GCCACCACAC TCCATCCAGC CTGGGTGACA GAGTGAGACT CCATCTCAAA GCAAAAAAAG
22080


 


AAACATAGGT GGGACCCTTG GTGTGTCCTT AGGGCATGAT GGTTGAGGTA TACTGCTGGT
22140


 


CCTGTCATGT AAAAGAAAAC GAGCCGACTC TGTGTCTACT GGAGAAAGCA CTGCATATAT
22200


 


CAGCCACAGT CAATACCTCG CTTCTGCAGG GACGGTGGCT GCCAGAGTGG GAGGCTTTGG
22260


 


TAGCACCCAT GTCGTGGAAT CACAATGTTG TCGATAGCTC TGGGGTCTTG TACAAAATGC
22320


 


CAGATCCTCC CATTTGGTTT CCTTATGGGA AGGATCGCAG TACTATAATA CATGGGCTTG
22380


 


TGCAAGGGAT CATTATACCC TTTTCTCTTT TTTTGCTTTT CTTTGAGACA GAGTTTCACT
22440


 


CTCGTCACCC AGGCTGGAGT GCAATGGCGC GATCTTGGCT CACTGCAACC TCCACCTCCT
22500


 


GGGTTCAAGT GATTTTCCTG GCTCAGCCTT CTGAGTAGCT GGGATTACAC ATGCCCGCCA
22560


 


CCAGGCCTGA CTTATTTTTG TATTTTTAGT AGAGACAGGG TTTCACCAAG TTGGTCAGGC
22620


 


TGGTCTTGAA CTCCTGACCT CAGGTGATCC ACCCACCTCG GCCTCCCAAA GTGTTGGGAT
22680


 


TTCAGGCATA AGCCACCAGG CCCAGCCTTT CTTTCTTTTT AAAATTAATC TTTGTTTAAA
22740


 


AATACTCTCA TTTTTTATTT AATTGTAGCA CTCCTAGATC CCGAAAGCAG ATACACTCTT
22800


 


GTTATGGGTC TGATTCTTTT CATTGCTTCA CGCCTTAGAG GATATTGTCC AATACTGGAT
22860


 


AAAAGTTTAC TCAGGTCTAC TTCCACTTTA ACGGGGATGG CTGAATATCT CTTCCACTTG
22920


 


GCTGTTTGTT TATAATGAAC TGACAAACAT ACAAATTTTC TTGAGTTCTG TGAGACATTC
22980


 


TAGTAAATCA TCTAACCTGA AGAGCAGGTT GTGAGAACCC CTGATTTAGA AAGCCCAGTG
23040


 


GTCATAAATA TAAGTGGCTC TGGACTGGCT CCCGGGGTCT GAAGTGTGGG CAGTCGGTTA
23100


 


GGATTGAGCC CTTGTAATTT GTAGGATCTC ACACACACTC CAGGAAGGCA GTGTCAGAAT
23160


 


TTACCTGTAT TATATTGGAC ACCCAGTTAG CGTTTGGAGA ATTGGTTGCT GGTATAGAAA
23220


 


AATACCAAAT ATTTTATGTC AGGGGAGTGA AAGAAAAAAC AAAAACCCGG CCGGGCGCGG
23280


 


TGGCTCACGC CTGTCATCCC AGCACTTTGG GAGGCCGAGA CGGGCGGATC ACGAGGTCAG
23340


 


GAGATCGAGA CCATCCTGGC TAACACGGTG AAACCCCATC TCTACTAAAA ATACAAAAAT
23400


 


TAGCCGGGCG TGGTGGCGCG CGCCTGTAGT CCCAGCTACT CGGGAGGCTG AGGCAGGAGA
23460


 


ATGGCGTGAA CCCGGGAGGC GGAGCTTGCA GTGAGCCCAG ATCGCGCCAC CGCACTCCAG
23520


 


CCTGGGCGAC AGAGCGAGAC TCCGTCTCAA AAAAAAAAAA CAAAAAAAAA AAACAAAAAA
23580


 


AAAAAACCCA TACACTTTAA GGAAAGCAAC TGACAGCATT TGTTACCAGT GATAAAATTT
23640


 


GAGCTTTGAA GTAAGAATAA CAATTTTGCC ATTGTGCCCC GGCCAAGAAA AAAAAAAGAA
23700


 


TTTTGCCATT GTGAAAGGCT TCCCAGTACT TTCTGATGAG CTTGACGGTG ATATTAACAA
23760


 


ATAACTTTTT TTTTTTTTTT TTGAGATGGG GTCTTGCTCT GTCACCCAGG CTGGAGTGCA
23820


 


GTGGTTCAAT CTCAGCTCAC TGCAACCTCC GCCTCCCAGG TTCAAGCGAT TCTCCTGCCT
23880


 


CAACGTCCCA AGTCGCTGGA CTACAGGTGT GCGCCACCAC GTCCAGATAA TTTTTGTATT
23940


 


TTTAGTAGAG ATCGGGTTTC ACCATGTTGC CCAGACTGGT CTCAAACTCG TGACCTCAGG
24000


 


CGACCCGCCC ACCTCGGCCT CCCAAAGGTG GGAGGCCTTG CTGGGATTAG AGGTATGAGC
24060


 


CGCTGCACCT GGCCTCTTGT CCTTGTGTTT TGCAGTGATG CAATGACCAT GTCTTACATT
24120


 


TGCAACCAGA AAAAAAGGTT AGTGTAACAA TGTTTATCCT GTTTTTCCCA GACTAGACAT
24180


 


TATGAAGATT AAAAAAATTT GAAAGTGTTT TGAATATAAT AAACTATGCT ATACACACAA
24240


 


CATTTTGGTG ACTAGAAATA CAAGTTTATT GTTTGTTGTT TGTTGAGACA GGGCCCTGCT
24300


 


CTGTCTCCCA GGCTGGGTGG CACAATCATG GCTCACTACA GTCTTGAACT CCTGGGCTTA
24360


 


AGCGATCCTC CCACCTCAGC CTCCAGAGTA GCTGGGACTG CAAACGAGCA CCACCACGCC
24420


 


TGGCTAATAT TTGTATTTTT TGTAGAGATG GGGTTTCACC ATGTTGCCCA GACTGGTCTC
24480


 


AAACTCCTGG GCTCAAGCAA TGCTCCTGCC TCGGCCTCCC AAAGTGCTGG GATCACAAGT
24540


 


ATGAGCCACT GCACCCGGCT GAGTTTCTGT TGTTTTAAGC CGCTTCATTT GTGGTACTTC
24600


 


TTACAGCAGT CCCAGGAAAC TGAGCAACTG CAGAACATCA AAATTGTTTT TCTTCAGCAA
24660


 


AAGGAGAAGC ACTTGTGGTT GGCACCAGCT TTTCCTGTGC TCACTTCTGC ATGGCCGCAC
24720


 


CTTTGCCCGA CACGAGTGCA CAGCAGGCTG TGGGGGAGCA ACTGGTTGAG TCAGGCCTCC
24780


 


ACTTGTGCCG TATCCCCACC TGCTTTGCTG GACACCCCTG TTTGGGGGGC ACCCACTGCT
24840


 


GCCCCAGACA CCAAGCAAGC ACCAGCTGTG TCCAAAACTT ACAGTCACTG TCTTGGCCCG
24900


 


TTTTGTGCTG CTGTAACAGA ATGCCACAGA CTGGGTAATT TAATACAGAA CAGAAATTTA
24960


 


TTTCCTCAAA GTTTTGGAGG CTGGGAAGTC CAAGAGCAAG GGGCCATCAG GTCAGGGCCT
25020


 


GGTCTCTGCT TCCACGATGG CACCTTGACC ACCGTGTCCT CACGTGGTCA GAGAGAGCCC
25080


 


ACTCCCAGGA GCCCTTTTAA TAGAGCAGAA CACTGCTGCG CTGCGGTTAA GTTTCCAACA
25140


 


CGTGAACTTC GGAGGTGACA CATTCAGATC ATAGCAGTCA CTCTAGGCAC AGTGTCTGAT
25200


 


GTGGTTTTAA AATACGTTCA CAGACTGGCC GGGCACTGTA GCTCACGTCT GTAATCCCAA
25260


 


CAGTTTGGGA GGCCAAGGTG GGTGGATCAC CTGAGGTCAG GAGTTCAAGA CCAGCCTCAC
25320


 


CAACATGGTG AAACCCCATC TCTACTAAAA ATACAAAATT AGCCAGGTGG TGCATGCCTG
25380


 


TAATCCCAGC TACTCGGGAG GCCGAGGCTG GAGAATCGCT TGAATCCAGG AGGTGGAGGT
25440


 


TACAGTGAGT CGAGATCATG CCATTGCACT CCAGCCTGGG CAACAAGACC GAAACTCTGT
25500


 


CTCAAAAAAT AAAATAAAAT AAAATACATT CACAAGGCCG GGCACTGTGG CTCACGCCTG
25560


 


TAATCCCAGC TACTTGGGAG ACTGAGGCAG GAGAATCGCT TATAACCTGG GAGGTGGAGG
25620


 


TTGCAGTGAG CTGAGATCAC ACCGCTACAC TCTAGCTTGG GCAACAAGAG TGAAACTCCG
25680


 


TCTCAAAAAA GTAAAATAAG GCCCTGCAGG CATGGTGGCC CACACCTGTA ATCCCAGCAC
25740


 


TTTAGGAGGC CAAGGCGGTC GGATCACGAG GTCAGGAGTT CGAGACCAGC CTGGCCAACA
25800


 


TGATGAAACC CCGTCTCTAC TAGCCTAGCC AACATGGGGA AACCCTGTCT CTACTAAAAA
25860


 


TACAAAAATT AGCCGGGCAT GGTGGTGCGT GCCTGTAATC CCAGCTACTC AGGAGGCTCA
25920


 


GGCAGGAGAA TCGCTTGAAC CCAGGAAGCA GAGGGTGCAG TGAGCCAAGA TTGCGCCGCT
25980


 


GCTCTCTAGC CTGGGCGACA GAGCGAGACT CCATCTCTAA ATAAATAAAT AAAATAAGAA
26040


 


AATAAAATAT GTTCACAAAT CCTTTGACAT TCCTCACCTC AAAAGCTGGA ACCCAACTCC
26100


 


CTCCTAAGCA TGAGTCTTCT CAGTGACTCA CTTCTAACAG CAGAACTTAC ATGGTTCCCC
26160


 


ACACCCAGAG GACATTGGGT TCCTCCCAAT ATCCCCCCAC CCAGCGACCC CCACCCAGGT
26220


 


CGCTGGCTTT GGGTCCCCCA GAGCCATGTT TCAAGGACAC TCAGGCAGCC CCTGGATGTC
26280


 


CATGTGGTAA GGAATGAAGG CCTCCTGCCT GCAGCCTCGG GAGGGAGCAT TCTCAGAAGA
26340


 


GGATGCCCCA CCTCCTGCCC AGCCTTCAGA TGGCCAGGAC CTCGTCCAAC GTCCTGACTG
26400


 


CAACATCATG AGAGACTCCG AGCCAGAAAC CCCCAGGTTT TGTACTCCTG ACTTATGGGA
26460


 


ACTGACAGAT AATGTTCGTT GTTAATTAAG GGGTGACTTG TCACACACAA TAGGTCACTA
26520


 


AACAGCTCTG TCTGGCCTCC CAGGAGGAGC CTGCCTTTCC TTTTCTTCAT GGGAAAAGTG
26580


 


CGATCAGTTT GTGAAGGAAT GTCCGCCCCC ACTTGATGCC AGAGGCTCCA CATGGTGACT
26640


 


GTCATAAACT CCATCTGCCC TCAGTGCCTT GCCAGCACCC GGCCTGCGAT CAGCTTGGTC
26700


 


TTGCGGGAGG CCAAGGCCCA CGTGTGTTTG TGTGTGGTGT CTGTGTCTGC GTGCCCATGC
26760


 


ATGCCCAGGG TACAGGGATG CCATATACAA ATTCTTTCAA TGTTGTATGT GGCATGTGTG
26820


 


TGTCTGTATG CCCAGGATAC AGGGATGCTA TATACAAACT CTGTTTTTTC GTTTTTTTTT
26880


 


TTTTGAGACA GAGTCTTGCT GTTTCGCCCA GGCCGGACTG CAGTGGCGCT ATCTCGGCTC
26940


 


ACTGCAAGCT CCACCTCCCG GGTTCACGCC ATCCTCCTGC CTCAGCCTCC TGAGTAGCTG
27000


 


GAACTACAGG CGCCCGCCAC CACACCCGGC TAATTTTTTG TATTTTTAGT AGAGACGGGG
27060


 


TTTCACCATG TTAGCCAGGA TGGTCTTGAT CTCCTGACCT CGTGATCCAC CCGCCTCAGC
27120


 


CTCCCAAAGT GCTGGGATTA CAGGCATGAG CCACCACGCC TGGCCTACAA ACTCTTTCTT
27180


 


TTTTTTTTTT TTTTTTTTGA GATGGAGTCT CACTGTCTTC CAGGCTGGAG TGCAGTGATG
27240


 


CGATCTCAGC TCACTGCAAG CTCCACCTCC CGGGTTCATG CCATTCTCCT GCCTCAGCCT
27300


 


CCCAAGTAGC TGGGACTACA GGCACACACC ACCACGCCCA GCTAATTTTT TGTGTTTTTA
27360


 


GCAGAGATGG GGTTTCACCA TGTTAGCCAG GATGGTCTCG ATCTCCTGAC CTCGTGATCC
27420


 


GCCCGCCTCG GCCTCCCAAA GTGCTGGGAT TACAGGCGTG AGCCACTGCG CCCAGCCTGC
27480


 


AAACTCTTTC AATGTCTTTC TTTTCTCTCT CCTGCCATCT TCTCCCTTGC AGATTTCTTT
27540


 


TGTCTCTACG TCTTCCCCAG CTGAGTCCGA GGTCCTGACT TGCCCACGCT CCCTGGACTG
27600


 


GAGGAGAGGT GATAGCAAGA GCTCCTTCAA GCCCAGGAAT GCCACCAGGG CTGCCCCGGG
27660


 


AGAGGAGGAA GCTGGGTCTC TCGGGGTTGT GGGGACCAGA CACCCTTCTA AGACATGGAC
27720


 


TCAGCACAGA AAGTCTAGAC ATCCACTACA AACACATCTC CCTCCTAACA GGGGGCCCCT
27780


 


GGGCACCCCA AGTGGCTGTT TGGTGGGACA GGCATGTCCA TCAGTCAGAA TATCTTTATT
27840


 


TTTTATTTTT TATTTTTTAT TTTTGAGAGA GTTTCACTGG AGTGCAATGG CACGATCTCA
27900


 


GCTCCCTACA ACCTCCGCCT CCCAGGTTCA AGCGATTCTC CTGCCTCAGC CTGCCACGTA
27960


 


GCTGGGATTA CAGGTGTGAG CCACCACACC CAGCTAATTT TTTTTTTTTT TTTTTGAGAT
28020


 


GGAGTCTCGA GGCTCTGTCG CCCAGGCTGG AGTGCAGAGG CGCGATCTCA GCTCACTGAA
28080


 


AGCTCCGCCT CCTGGGTTCA CGCCATTCTC CTGCCTCAGC CTCCCGAGTA GCTGGGATTA
28140


 


CAGGCATGAG CCACCGCGCC CGGCCAATTT TGTATTTTTA GTAGAGACAG GGTTTCACCA
28200


 


TGTTGGTCAG GCTGGTCTTG AACTCCTGAC CTCAGGTGAT CCACCTCCCT CGGCCTCCCA
28260


 


AAGTGCTGGG ATTACAGGCC TGAGCCACCA CGCCCAGCCC AGAATGTCTT CTTACTTTTT
28320


 


ATTACTCTGT CCCCCATCCT GGGTCCAGAC CTGTGACCGT GAACAACCGG CTGCCCAGGG
28380


 


GTGAATGGGG TGAGTGGGGT GAGTCCACAG AACAGTGGGG TGCAGCCCCA GGGGTCTCGT
28440


 


AGCACCTGCC CCCAGGTCAG GAAGTCCCAC AGCCTAGAGG CTCCAGCCTC AGATGCATAC
28500


 


ATATGTAGGC CCTGCCCTTT CCTCCTGAGC GGCGGGCCAC AGAGTCCTGA ACAACAGGAA
28560


 


GCCCCTGAGG AGGGCTCCGC CCTGAGGGAG GGCAGGGGAG CCCCCGCCAG CCCCACCCAC
28620


 


AGCAGCGGGC CCTGCCACCC CCCACCCTGA CACCTCACCC CTTGGATTCC AGAGAGGAAA
28680


 


GTGGGCTTGT GTGTAGTTTA CATGCTCATA TCTTAAAATC ACCGTTGTCA ATAGAACAAT
28740


 


TCATAATAAT GATGATAAAA TAAGATTTAT AACCAGCTTC AGTCTGGAGA TACACACAGA
28800


 


GCAGATCTTC ACTCCCAGAC AGGGAGCCCG CAGCTGCCCC CGACCCCACA GGTGCAGGAC
28860


 


ACACACAGAC AGTTCAACCA TGTCTTAAAC ACACAGGTGT TTATTTAATT GTTCATTTGA
28920


 


TTGAATTTTT AAGTTCACTT TACTACGTGG ATGAGATGGG TGCATATTAC AGTAGGCTTT
28980


 


CGCTATGAGC GCTGCCACCA TGAGGAATAT CCCAGCCCTC AGTTCTGCTT CCCTTTCTGA
29040


 


GTCCCACAAA AGCCAGATGT GGACAGCCTT GGGTTCCCAT CCCAGCTGGC TGCTCCTTCT
29100


 


GGGGCTGTCT TGGTGGGGAG AGGGAGATGG GGCAGTGGGT CCCTGCTGAC CCCTGAGCCC
29160


 


TGCAGGGGTC AGGATCCTCC CGTGGTCCCT GGGTGTGGCT CTGGAAGACA CTGGCAGTGC
29220


 


CCGGCCAAGG CCTCCCGCAG GATGGAAGTT GAGGGCCCTG GCTCTGGGTC CTAAGAGAAC
29280


 


TCAGCCGCCC CCTTCACACT TTACAGCAAG GGGCCAGGCA GCAGCTTTGG GATGGGGCTT
29340


 


CCGTGGAGAA GTGGGGGATG CTGCAGTGGT ACAAAGACAG CCTCCCCCAC CGCCATCCTC
29400


 


CAGCTGACCG TCCTCCAAGG CCAGCACTGG GCGTCCAAGG GAAAGAAGGA ACTCAGCCCA
29460


 


GAGGGTGTGG GCAGGAGAGG CCTGGAGTCA GGCCTCCACC CACAGCCCCC TCTGGGTGCC
29520


 


AAGTGGGAAG GGTGTTGGGG CTGGCTTGGG AACCTTACCC GCTGCCCTTC CAACACCTGG
29580


 


ATCTGTGGGC AGCGGTCCCA CAAAATCCCC CTTGGGGCTC CCTGAGGAGG ACTTCTGGCT
29640


 


GCCGCTTCCA CCAGGGCAGA GGGCACAGGA GGGGCCAGCA CTCCAAAGGG CTCTAGGGTG
29700


 


GGTCTTTCAA GGACATCTGC AAAGCCCTGG TGGGGAGGGG CCTGGGCCAG AGGCTCTTTG
29760


 


GAACTCTTGC ACTTCTGAGT GGGGGACTGT CCATGCTGCC CACAACCTCT AGACCATGCA
29820


 


GCCTGCTCAT GGGTCCCTGG CAGAGAATGC CCACTCCCCA GCAGACTCAG GGCAGGCCCC
29880


 


CAACTGCAGG CTTCCAGGAA GGCCCAGGGT GTCCACCTCA CGCCAGGTGG TCTCAGAGGA
29940


 


CCCCTGTGCA ACCACATTAA GGAAAGCTGC AGCCCCCACC CACCCGCCTG CCAGTTCAAC
30000


 


AAGCACCGGC TGCACACGCA GGCTCCCAGG CACCATCACC CCCCTCCCCC GTCGCCCCTC
30060


 


CCTCACGGGG AGCCCCTTCC CCCTGGAAAG ACAGCAGGTA CTGTAGCCTC GCCTGCTGGC
30120


 


CAGGGGCGCC GGCTCAGAGG ACCTGCCCTG ACCTGCACCT GCTGACCAGA CAGCCCAGCG
30180


 


TAAGGACCCG CGATCCCACG CCACCGCCCT GGGTTTACCA CGGTCACCAC CACCTCTCTC
30240


 


ACAGGGCCCC CGGGGGACCC AGCCGCGCCC GGCCTGGTGT CTGCACCGAG GGACCGCGTC
30300


 


TCACGCCCGG CGGCTCCTGC AGGGGAAGCC GTGGTCAGCG ACTCACCACG AGGACAGGGC
30360


 


AGGGCGGCTG AGTGCGGAAG AGAAGCATCA AGCTGGGGGC GGGGGTGGGG GAGGAGGAAC
30420


 


AAAAGTTGCA TCTAGACAGA GGTGAACGAA ACAAAACCAA AACCCGAACG TGTTCCGTCG
30480


 


CAGGATGGGC GCCGCCCGTC CCGGGCCCTT AGCCCGACAT CTCTTCTCGC TGCTCCTTGT
30540


 


TCCTGCGCAC CTCGGCCGCG TGCAGCTCCT GCAGGACAGG GGGCGGGAGG GCCTGAGGGC
30600


 


GGGGGTGGCT TGGGGCGACT CCGGGAACCC CCAGGCGCGC AGGCCGTGGC GCCCTGGCAC
30660


 


CCGCCCGGCC TCATCCGGGC TGGCCTTCGG CAGGACCCTG ACTGAGTTGA GGGGGCGGGA
30720


 


GCACCGGGGA GGCGCAGAGC AAGGCCAGGG ACCAAGGACG GGTTTCCTGG GAGCTGGCTG
30780


 


GGCCCCGCTT CTAGCTCGTA CCGGAGCCGA GCTTCCTTCA GGGCACTTTC AATATAATGA
30840


 


ATTTAGCCAT CTATTACTGC GGCTAGTTAC TGTCCCGCCA GGACCAGACT CTGGACCTGC
30900


 


CTCGTGCGCT GCTGGGGACG CCCAGTAAAC ACGGGAGGAG CCCCCGACCC CCACCCCAGC
30960


 


TCAGCGCCTC GGAGTCCCCG GCCCCGCTCT GCGCCCCTCC GAGCTCCGCC CTAGCCCCGC
31020


 


CCCCGCCCAG TGCCCCGCCC CCTGCCTGCT GCTAGCCCTG CCCCCGCCCC GGCCCCTGCC
31080


 


CGCTCCGAGC TCCGCCCTGG CCCCGCCCCG GCCCCTGCCC GCTCCGAGCT CCGCCCTGGC
31140


 


CCCGCCCCCC GCCCAGTGCC CCGCCCCCTG CCTGCTGCTA GCCCTGCCCC CGCCCCGGCC
31200


 


CCTGCCCGCT CCGAGCTCCG CCCCGGCCCC GCCCCGGCCC CTGCCCGCTC CGAGCTCCGC
31260


 


CCTGGCCCCG CCCCCGCCCA GTGCCCCGCC CCCTGACTGC TGCTAGCCCT GCCCCCGCCC
31320


 


CGGCCCCTGC CCGCTCCGAG CTCCGCCCCG GCCCCGCCCC GGCCCCTGCC CGCTCCGAGC
31380


 


TCCGCCCCGG CCCCGCCCCG GCCCCTGCCC GCTCCGAGCT TCGCCCCGGC CCCGCCCCGG
31440


 


CCCCTGCCCG CTCCGAGCTC CGCCCCGGCC CCGCCCCCGC ACCTTCTCGC GCAGCCGCTC
31500


 


GCGCAGTGCG GCCAGGTGTG CCTCGCGGAT CTCCTTGCTG AGCTCCATCT TGTAGTTGAG
31560


 


CTTCTCCTCC GCCTGGCGGC TGAAGTTGTT ATTCTCCTCC AGCGCCTTGT GCAGCACCTC
31620


 


GCGCTCGTGC TCCCGCCGCT CCGCCAGCTG CTTCAGCACC TGCGCCTCCT GCCTCTGTGC
31680


 


GGGGCCGGCG GGCGCGCGTG AGCGGCAACC CCGGGCCCTG CCCGGCCGGA CTCCTCCCTG
31740


 


CTCTCCGCCT CCCGCCCAGC GCCCGCTCGC CTCACCTGGC GCCTCCACCT GCCCAGGCCT
31800


 


CGGTGGGCGC CGGGACCCCC GGGCGCTGCC CTGGGAACCC TCGCCTGCCA TCCGGCCTGT
31860


 


GGTCGGGGCA GGGCCAGGGG GTCGCGATCC GCCGCCCCCG CCCCCGTCCC TGCCTCGCGC
31920


 


GCGGGTCCCG CGCTCCTGGC TGCGCCCAGG GCCCCCGCCA TACCCTGCCG CCACTGCACA
31980


 


CCCTGCCCTG CGCGTCTGCC CCTCCAAGGA CCAGCAGCAA GAAACCCTAA ACTTGTGGGC
32040


 


GGTCTCTGAG CTTTGTCTCT TCCTCGGACA TCCGCCCACT GAGCAGAGTA GCTGCTTGTT
32100


 


ACACACCGGG TTCCCAGCTC CCAATTAGGT GCCCAGGAGC GGAGGGTCCC CAGGGATGCT
32160


 


GGGGGAGGGG CCGGCTGGTG ACCCCTGGGA GGAGAGCGGG GCAGCAGGAC CCGCACCCAC
32220


 


ATGCCAGTCC CTACTAGTCA GCCCTGTGAA CCCTGGTCTC TGGCCTCACC GGGAAGGGAA
32280


 


CGGAGCCGCT TCCCCTGCCC AATGCGTTGG CCTCCAGGGT GGCACCCCCA AAAGGACATT
32340


 


TTTATCTCTG TTTCAGTCTC AGAGGGGCTG GTGGGAGGGG AGGCTGCAGG GAGGGGACCT
32400


 


GGAGCCCACA CCCACCTCTC CCAGGGCCCC TCCGCCCTCC AGCAAGCCTC AGGGTCTTCA
32460


 


CACATGAGGC CCTTCCTCCA GCTTCCCTGT CTGGGAGAGG GATGCCCCAC CCGACGTCCC
32520


 


CAGGGCCCAT CTGGGGACCA CCCCCTAGCA TCCTGCTGGC CCTGACAAGG GTGCCTCCCA
32580


 


CCCTCACCAG AGGCTCCTGC TCCTTCCAGG TGGCCGCCTC GGAACCCTTC CTCCTCTCCA
32640


 


TCCCTTTCTT TTTTTGTTCT TGTTTGTTTT TTGAAATGGA GTCTCACCCT GTCGCCCGGG
32700


 


CTGAGGAGTG CAGTGGCGCA GTCTCGGCTC ACTGCATCCT CCACTTCTTG GGTTCAAGCA
32760


 


ATTCCCCTGC CTCAGACTCC CTAGTAGGTG GGATTACAGG TGTGCACCAC CACACCTGGC
32820


 


TAATTTTGTA TTTTTAGTAC AGATGGGGTT TCACCATGTT GGCCAGGCTG ATCTTGAACT
32880


 


TCCAACCTCA AGTGATCTGC CTGCCTCAGC TTCCCAAAGT TCTGGGATTA CAGGCGTGAG
32940


 


CCACCACACC CGGCCTCTCC CCATCCCATT CTTATCTCTC AGAAAGAGCC CCAGGGAGCC
33000


 


ACAGCCCCTC CTGCTCCAGG CCAAGGCACT GACCAAGCCT GTCCGGGAGC ACCCTGCTTC
33060


 


TTGCAGGCCC TGTCCCCGTG GGCCGCCTCC GTTGAAACTC CTGGGGGGTG GGGGATGGAG
33120


 


GACTCCTTGC CTTCCTCCGC TCCTCGGCTG CCTCCAGCCG CTTTTGCAGC TCCTCCAGGG
33180


 


AGGTGTCCTT CTTCTTGGGT GGGGAGGAGA GCATAGGGCT CTCTGGGGAC AGGTCAGAAG
33240


 


GGGACTTGAG GATGACCTCG AAGCTCTGGC CTGAGGCCCG CTTGTCCAGC TGCTTCACCT
33300


 


CCATGTCTGC AGGGCAAGAC CAGAGTAGAG CTTCAGAGGC CCGGCCAGGG CATGGCGTGG
33360


 


GCTGAGCGGG ATGCTCCCAG CACACATCCA ACCCCAGGGC TGGGCGAGAG GGGGTGGCTG
33420


 


CTCCCGCAGG AATCCCAGGC TTCAGCCCCC AGGATGGGCC CCTTCCCCCT AGAACCTCCC
33480


 


TCTCCAGAGG CAGCCAGGAC GGGAGTTCAG AGAGACTGCC GGAGGCCGGG GGAAAAGGTG
33540


 


AGGTGGGCAG GCACCGCAGG GAAGGGCAGG CGGCAGCCAG GCACTCACCC CCGTACTGGT
33600


 


AGACGGTATT GGGGTGCGGC TGTGTGTAGA AGCAGGAGCA GATGAGCGAC AGCACCGACA
33660


 


GCTCCTTCAT CTTCTCCTTG TAGGCTGTGG GCACAAGGCT GGGCTGAGCA AGCACCACTG
33720


 


GGGCCTGCCC ACCTGGGCCC CCGTTTTCCC TCCCCATGGC TGCCTCTATC ATGTCTCTGT
33780


 


GAGACACGGA GCTGCCCAGC ACGCTCTCTT GTGTGTCTCC ACACCGCCGG CCCCTTCGTC
33840


 


TCTCCAGCTC TCTCGCTTCC AGACGTCGGC ACTGTCTCCG TGGTGTGTCC CCTGCCTTCT
33900


 


GTCTCTCTCG CCCTCTGCCT CTCCCCGCTT TTCCTCTCTC TCGGCATTAA TGTCTGTCTC
33960


 


ATCTTCCACA CTGACTTGTT TCTCCATCCT TCTCCTGCCT GCTGTGGTCT GAATGTTTCC
34020


 


ATTACCCAAA ACTCATGTGT TGAAATCGTA ACCCCAAGGT GCCGGTGTGC GGAGGTGAGG
34080


 


CATTCGGAGG GAATTAGGCC ATGAGGATAG AGCCCTCCTA AGTGGCCCCA GAGTGGGGCT
34140


 


TCAGAGAACT CCCTCACCTT CCATCATGTG AGGACACAGC CAGAAGACGC CACCCGTCTA
34200


 


TGTACCAGGA GGCGAGACCT CTCCAGGCAC CGACTCTGCC GGCACCTTGA TCCTGGACTT
34260


 


TCTGGCCTCC AGAGCGATGG GAAATAAGTT CCTGTCGTCT ATAAACCACT CAGTCTCAGG
34320


 


TACCTGCCCA GACTGACAAA GTGGCTACCC CTGCCTGTCT GGGTCTCTGT TTACCTTCTG
34380


 


TGTGTCTGAC TCTGTCACTG TCATTGTATC TTTCTGTGTC TCTGGGGGTA GCCCCTGACT
34440


 


CTGTCTTTCT CCCTGAGTGC ATCTTTCTGT GATTCCTTGT CACTGTGTGT CTTTCTGACT
34500


 


CTTACCTCCC TCTGTCCCGC TACTTCTCTC TCCCCTCCTC CTCCTTCCCA CTCCTCGCCA
34560


 


GCTCAAGCAG GCAAGATTTA CTCATGACGG GACCAGCACA GATGCAAACC CTCTGTGGGC
34620


 


AGGACTTTCT TGGGCTGTAA ACCTGGATGA AGCCCTCAGA CCCTCCTTTT TCCTTCCCAA
34680


 


TGATTGTGTG GTCACCTTGA GATGAAACCA GGCCCTCTCC AGGCACATGC TCTCTGTCTA
34740


 


TCTAGGGCTG GGCTTGGGCC ACTGATGCCA CCAAGGAGCA AGGGAGGGAA GCTGTCCGTT
34800


 


CAGGACCACA GCCAGCCCTC TTGCCCATTC AGGTCAATCA AGTGCCCACC AGCCAGTGTC
34860


 


CCTGCTGCCC AACCCAAACC AGAAGCAAGC CGGGCTCCTG TGGCCCTGTG CCCTGTCAGG
34920


 


GGAAGAGGAA GGCGCCTGCT GTCACAGTGA AAATAATTTA GCTCTTTTGG TCTATTCAGG
34980


 


GCGAACCTCA TTCCTAAGCA GACACGCTGG CCCGGTTTCT CACTAGTGCT CGATAATCCT
35040


 


TTTGGCTGGG TGCAGTGGCT CATTTAACTG TAATCCCAGC ACTTTGGGAG GCCAAGGCAG
35100


 


GTGGAACACC TGAGGTCAGG AGTTTGAGAC CAGCCTGACC AACATGGTGA AACCCGATCT
35160


 


CTACTAAAAA TATAAAAATT AGCCAGGCGT GGTGGCAGGC ACCTGTAATC CTAGCTACTT
35220


 


GGGAGGCTGA GGCAGGAGAA TCGCTTGAAC CTGGGAGGCG GAGGTTGCAG TGAGCCGAGG
35280


 


TCGCGCCATC GCACTCCAGC CTGGGTGACA GTGTGAGACT CCGTCTCAAA ACAGAAAGAA
35340


 


AAAGAGAGAG AGGAAGAAAG GAAGGAGGGA GGGAGGGAGG AAAAGAAGAA AGGAAAGGAA
35400


 


AGGAAGACAG ACAAGGCAGA AGTAATCAAG CCTTTCATGG TGAGCTGGGT CTTCTGGTGA
35460


 


CAGTGCAGAG AATGGTCTGT CCTGACTTAA ATTTCCTGGT GACCTACACT TTTCTGGACA
35520


 


GAGCAGCACA GAGCCCAAGA GGGTGTAAGG AGGAGCAGAA AGGAATCCCA GGGTGGGCAG
35580


 


GCCCGTGCGA GAGCCTTTGG GGGAAGGAAT GAGACTTTGA GCCGGGAAGC GAGGCAAAGC
35640


 


TACCTGTCTT GGTCATTGTC TTCAGGGAGG GAGATGGAGG GGGACCAGGT GGGGGAGCCT
35700


 


CACAGGGGAC TTTGGTCTGA CTTGTCAAGT TTTCTTTTTT TCTTTTTGAG ATGGAGTCTT
35760


 


GCACTGTTGC CCAGGCTGCA GTGCAGTGGT GCGATCTCGG CTCACCGCAA GCTCCGCCTC
35820


 


CTGGGTTCAC ACCATTCTCC TGCCTCAGCC TCCCGAGTAG CTGGGACCAC AGGCACCGCC
35880


 


ACCACACCCA GCTAATTTTT TGTATTTTTA GTAGAGACGG GGTTTCACTA TATTAGCCAG
35940


 


GATAGTCTCG ATCTCCTGAC CTCGTGATCC GCCCGCCTCG ACCTCCCAAA GTGCTGGGAT
36000


 


TACAGGTGTG AGCCACTGTG CCTGGCCTAC TTTATTTTTT AGAAACAGGA CTGTGCTCTG
36060


 


TTGCCCATGC TGGAGTGTAG GGTGCAGCTG TGCGGTTCAC TGCAGCCTTG AACTTCTGGG
36120


 


CTTGACGGAT CCTGCCATCT TAGCAGCTGG GACTACAGGT GCATGCCAGC ACACCAGTTT
36180


 


TCTTTTTTTT TTTATCTCTG CTCACTGCAA TTCCGCCTCC TGGGTTCTAG CGATTCTCCT
36240


 


GCCTCAGCCT CCCAAGTAGC AGGGATTACA CGCACATGCC ACCACACCCG GCTAATTTTT
36300


 


GTATTTTTAG TAGAGACAGG GTTTCACTAT GTTGGTCAGG CTGGTCTTGA GCCACCGCGC
36360


 


CCGCCCGGCC TACACACCAG CTTAAAAAAA AGAAAAAAAT AGCTGGGCGT GGTGGCTCAT
36420


 


GCCTGTAATC CCAGCACTTT GGGAGGCTGA GGCAGGCAGA TCACCTGAGG TCAGGAGTTC
36480


 


AAGACCAACC TGGCCAACAT GGCGAAACCC TGTCTCTACT ACAAATATAA AAATCAGCCA
36540


 


GGCGTGGTGG CGGGCTCCTC TAATTCCAGC TACTTGGGAG GCTGAGGCAG GAGAATCACT
36600


 


TGAACCCGGG AGGTGGAGGT TGAAGTGAGC CAAGATCGAG CTACTGCACT CCAGCCTGGG
36660


 


AGCAAGACTC CCGTCTCAAA AAAAAAAAAA AAATTTGTAG TGGTATGGAG GCCGGGCATG
36720


 


GTGGCTCACG CCTGTAATCC CAGAACTTTG AGGGGCCAAG GCGGGCAGAT CATGAGGTCA
36780


 


GGAGTTCGAG ACCAGCCTGA CCAACATGAT GAAACCCTGT CTCTACTAAA AATAACAAAA
36840


 


ATTAGCCAGG CATGGTGGCG GGCACGTGTA GTCCCAGCTA CTCGGGAGAC TGAGACGGGA
36900


 


GAATCGCTTG AACCCAGGAG GCAGAGGTTG CAGTGAGCTG AGATCACGCC ACTGCACTCC
36960


 


AGCCTGGGTG ACAGAGTGAG ACTCTGTCTC AAAAACAAAC ACAAACAAAC ATATATATAT
37020


 


ATACATGTAT ATATATAATA TATATATACG TATATATACA CGTGTATATA TATAATATAT
37080


 


ATACGTATAT ATACACGTGT ATATATAATA TATATACGTA TATATGTATA TATTAATATA
37140


 


TATACGTATA TATACACGTG TATATATTAA TATATATACG TATATATACA CGTGTGTATA
37200


 


TATTAATATA TATACGTATA TATGTGTGTG TGTGTATATA TATATGTATA TATATATATA
37260


 


TATATACATA TATATATACA GAGAGAGAGA GAGTAGTGAT AGGTCTTGCT GTCTTGTCCA
37320


 


GGCTGATCTT GAACTCCCGG CCTCAAGAGA CCCTCCCACC TCAGCCTCCC AAAGCACTAG
37380


 


GATTATAGGT GTAAGCCACA GTACCTAGCC TATTAAAAAT TAATGTTAAA CAAGAGGATG
37440


 


TGATGAGGGA GTTAGAGGGT GTGCCAGCCA TGTGTTCCAC AGCAGCAGGT CAGGAGACAT
37500


 


TGGGGACATT TAGAGGAGCT GAAGAGGTGG CCAACCCTGT GCTCAGGAGG ACGGGGGAGG
37560


 


GAGAGAGCAA GAGGGAGTTT GGGCTGGGGC AGAACGTACC TGGGTCCTGA GAGGATAAGA
37620


 


AGGTAGGGAC TTGGCCCCTC CAGGCCTGAC TCTGCCAGCA ACCAGCTCCC TATCAGCAGA
37680


 


CTCCAGGCCC CTACCCTTCA GCTCATCCTT CCTTATCACA CATCCAAAAC TCTGAATGTG
37740


 


GCCGGGCGCA GTGGCTCACG CCTGTAATCC CAGAACTTTG GGAGGCTGAG GCAGGAGGAT
37800


 


CGCTTGAGAA CAAGAGTTTG AGACCAGCCT AGGCAACATG GTGAAACCCC ATCTCTACTA
37860


 


AAAATATAAA AATTAGCTGG GTGTGGTGGC ACATGCCTGT TGCCCCAGCT ACTCAGGAGG
37920


 


CTGAGGCAGG AGAATCACTT GAGCCTGGAA GGCGGAAGTT GTAGTGAGCA GAGATTGTGC
37980


 


CACTGCGTTC CAGCCTGGGC AACACAGCGA GACTCTGTCT CAAAAAACAA AAACTGGAAT
38040


 


GTGTTTACCA TAAAGGCCAG AAAATGTGAT TAACAGCTGC TCAAAGCCCC TGTCTGCCCT
38100


 


AAGCCTGAAA TTTTCACCGA AAAAAAGATC TGTAGGCTCA TACAGAGGAA GGACAAACAC
38160


 


CAGGGAGGCT CTCTTCCAGT TTGCTTCACC TCAGCAAGCA GACGGCTGGC AGCAATTTGG
38220


 


GGGCAGGTGT GAGCACCTGC ATCATCAGGA AAGAAGGGGC ACGGTGGGGA CGCAGGTCAG
38280


 


ACCTCTCACA GGTCTTGGCT CTGCCCAGGA GACACGTGTC CAACTGAGAG GTGAGGAACT
38340


 


GGGTTCTGCA GCTGCAGACA CAGGTGCGGC TCAGCATCTG ATGGCCACGG AGACCCCCTG
38400


 


GCTTGGCTTC TCCCAGCTGG TGGCCCATGA GGAGCTTCTA TCCCAAGAGA CTGTCCCTCA
38460


 


AGGAGCAAGT GGGACCAGGT ACCCACAGGA CGGAGCCTGG GAGTGAGGCC TGCCCTGTGG
38520


 


TCTGGCTACA GGGAGGAAGG GCAGATTGGA GGGGGCAGGA CAGCAGGTCA GGAATTGGCC
38580


 


AACTCTGGAG AGAGCAAGCA AGGGGAAGTC TGCGCACAGG GCAGGGCTGG TCAGGGGCGA
38640


 


GGCAGGGCAT TGGACCAGTA TTTTCAGAGC TGGTGAGGCT TAAAGAGCAT GTCTACTGCC
38700


 


TCTTATTACA GAGAGAGGAT GCCGAGGCCC AGACCCATCC AGGCCACCTC TCCACAGACA
38760


 


CAGCTGGTGC CAGGGAAGCC CCTCCCAGAG CCTCAAGGCA TTGCTCCCTC TCTCTCTCTC
38820


 


TTTTTGTTTT TTTGGAGACG GAGTCTCACT CTGTCTCCCA GGCTGGAGTG CAGTGGTACA
38880


 


ATCTCGGCTC ACGGCAAGCT CCGCCTCCCG GATTCACGCC ATTCTCCTGC CTCAGCCTCC
38940


 


CGAATAGCTG GGACTACAGG CGCCCGCCAC CACGCCCAGC TAATTTTTTG TATTTTTAGT
39000


 


AGAGACGGGG TTTCACTGTG TTAGCCAGGA TGGTCTCGAT CTCCTGACCT TGTGATCCGC
39060


 


CCGTCTCAGC CTCCCAAAGT GCTGGGATTA CAGGTGTGAG CCACCGCGCC TGGACTTTTT
39120


 


TTTTTTTTTA AGACGGGGTC TCACTCTGTC ACCCAGGCTG GAGTGCAGTG GCGCGATGTC
39180


 


GGCTCACTGC AACCTCTGCC TCCCCAGTTC AAGTGATTCT CCTGCCTCAG CCTCCCAAGT
39240


 


AGCTAGAATT ACAGGCACAT GCCACCATGC CCAGCTAATT TTCTGTATTT TTAGTAGAGA
39300


 


TGAGGTTTCA CCATGTTGGC CAGGCTGGTC TTGAACTCCT GACCTCCGGT GATCTGCCCA
39360


 


CCTCAGCCTC CCAAAGTGCT GGGATGACAG GCGTGAGCCC CCGCGCCTGG CCCCCCGCAG
39420


 


TGCTGGGATT ACAGGCGTGA GCCCCCGCGC CCGGCCCCTC CCTCTCTTTG ACTCCCTTCT
39480


 


TTCTCACCGC CCCCTCCCCA CCATCCTTCC CCTTCACTGA CTTCAGGGAG TTAAAAACAA
39540


 


TTCTCGCAGT GAGCTGGGCT TGTTTTGTCT CCCTGCTTCT CTTTGTACTA AACATTAGAT
39600


 


ACCGAGGAAA TGCGGATTGG CCTTTGGATG ATTCATGAGC AGGAGTCAGA AAAAGGCACC
39660


 


AGGTTGGCCT CAAGCAGCAG GGTATAGTAG TGCCCGCTCC CAGGGTCACA CCTCACGCCC
39720


 


ACCCCTCCCG CCGTCCAGGT GGATGGTGCC CACTCCCAGG GTCACACCTC ACGCCCACCC
39780


 


CTCCCGCCGT CCAGGTGGAT GGTGCCCACT CCCAGGGTCA CACCTCACGC CCACCCCTCC
39840


 


CGTCGCCCAG GTGGATGGTG CCCACTCCCA GGGTCACACC TCACGCCCGC CCCTCCCACC
39900


 


CACCCGGGTG GATGGTGCCC GCTCCCAGGG TCACACCTGA CGCCCACCCG GGTGCATGGT
39960


 


GCCCGCTCCC AGGGTCACAC CTCACGCCCA CCCCTCCCGC CCGCCCGGGT GGATGGTGCC
40020


 


CGCTCCCAGG GTCACACCTC ACGCCCACCC CTCCCGCCGT CCAGGTGGAT GGTGCCCACT
40080


 


CCCAGGGTCA CACCTCACGC CCACCCCTCC CGCCGCCCAG GTGGATGGTG CCCACTCCCA
40140


 


GGGTCACACC TCACACCCAC CCCTCCCGCC CACCCGGGTG GATGCCCTTA TCAGCTCTCC
40200


 


TTCTCCTTCT CTTTCGTCTT CTTCGTCTTC CTCCTCTTCT TTCTTCTTTT TTTTTTTTTT
40260


 


TAGAAAGAGT TTCTACTCTT GCTGCCCAGG CTGGAGTGCA ATGGCACAAT CTCAGCTCAC
40320


 


TGCAACCTCC CTCTCCCCGG GTCAAGCAAT TATCCTGCCT CAGTCTCCCA GATTGCTGGG
40380


 


ATCACAGGAG TGTGTCACCA CACCTGGCTA ATTTTGTACT TTTAGCAGAG AGGGGGGATT
40440


 


TCACCATGTT GGCCAGGCTA GTCTCGAACT CTTGACCTCA GTTTATCCAC CGGCCTCAGC
40500


 


CTCTCAAAGT GCTGGGATTA CAGGCATGAG CCACCCTATC TGCCTCACTT CTACAGAGGA
40560


 


GGAATGAAGG CTCAGAGAGG GCAAGCATTC CACCCAGCAT CACACAGAGT GCCGGGTGAG
40620


 


AGCCCAGTCA TGAGCCTGGG CCTGACTGCA GGCTCCTGTT GGGAGCTCGC GGAGGTGGGG
40680


 


GATCTGTCCA GAACTGAGAG GCCAGGGGAC CACAGTGGCC TCTGACCCCT GGAGGGCCCT
40740


 


GGAGGCTGCT GCCGGCTCCC CCCGGGGGCA GATGGAGGTC ACTGTCACCC AGGCTGCTTC
40800


 


TCATGGTGCC AGGAGCACAG CATGGCAGGA GCCACCAGCC GATTTGCCTT TCCCTGGGCA
40860


 


GGAAACTCAG AAATGTGGCT ACCACAGTCA GGCTGCTTGA CGTGCGGTGA GCACTCATCT
40920


 


CTTAGCAGGC AAGCGGCCAA GCACCTTTCC TGAAATATTG AGGCCTCAGA ACAAGCCCCA
40980


 


GGAGAGGTGC CAGCACCGTC ATCTCTACCC AGATAAGGAG ACCCAGGTCC TGAGAGGTTA
41040


 


GGCAGCTCGG ACAACACCAC ACAGCTGGAG GAGGTCAGAC TCTGGGTTGC AGAAGGAGAA
41100


 


TGTGAGCAGA GGCCACAAAA GAGCGAGGAG CCAGTGCCCA GATGCCGAGA TGCCCTCGCC
41160


 


CTCCCAGCTC AGCCCCAGGA ACCGAGCCCA TGGGGAGGGA CCGTCAGGGA AAGGCTGTCA
41220


 


GGAAGGGCAG GAGGCGGCCC TGGAGAGGAC GGCGCTGCCC TCAGGGGCAG GAGGGGAGTC
41280


 


CCCTCCGCTG AGAGCCCCCC CACCCCCAGT ATCCCCGGGG GTGTCCAGGA GGAGGCGGAG
41340


 


GGAGGAAGCG CAGATGGACA GGACTCCCAG ATAGGGTGGG GAGGTGTGGC CGGTGACACA
41400


 


CACGGTCCCC TCCTGGCAGG TGCTGAAGTC ACCTGGAGCC TCCAAGCCCG TGGGGCCTGA
41460


 


GGGGCGGGGT CAGGTCGGGC ACGCGTGGGT GGGCGGAGTT CTGCGCCCCG GGCCAAGGCG
41520


 


CCCGAGTTGA ACCAGTCAGC TCGGGAGAGG GACCGCGGCG ACCTGTCCCG GGGGCGTAAG
41580


 


AAAAGGTGGG AGGGAGTGCG GCTCGTGAAC GGGGGCGGCG ATGGGAAGGA GGTGCGGCCC
41640


 


TTCGTCCTGT CCTCCCAAAC GTCGAGTGAA AAACGAAGCG GGTTCTGCGG CCTCGCGGCG
41700


 


GAGCAGAGCG TTTCGGGAAG GGCGGGCCCA GCGTCCTCGC GCCCGAGGTC GCCCGGCAGC
41760


 


TCCCCTGCGT CCACAATCCG CCCCCCGCCC GGGCCTGCGC CCGCCCCTCC GCCTGAGCTC
41820


 


CGCGCGGGAC GGGCCGGGAG GCCGGGGTGG GCGCTACCTT CGAAGGCGGT GGGTCCGCCC
41880


 


CGCGGGAGGT GGAGGGGCGG GAGGGGCGGA GCCCTCTGGT CTCCGGAGGG TTTGGGGATC
41940


 


GCAGTCGCCC CTCCCCCATC CAGACCCCGC GGCGCAAAGG GCAGTGGCTT TTCTGGCCAG
42000


 


AGCAGGTGGC GCGGGCGTCG CAAAGGGTGG TCCCCGAGGC CGCAGCGGTG TGGGGGGAGG
42060


 


GCGCGGTCCC CCTCACTCCG GGCTCCGCCG TGTCTGGCCC GCCCCCCTCC TTCAGCGCCC
42120


 


CCTCCAGCCC CTGTGCTGCA CTGGCGCGGG GAGCGCCGGG TTCCCGGCTG GGGCTTTGGC
42180


 


AGAGGGTCCC ACCCTCTCCC CGCCTCCCCA CGAAGGCTCT GGCGGACCCA GATCTCGGGT
42240


 


CGCCGGACGC CCCAGGGACC CCGCCCGCAC ATCGCGAGCG CGCCCACCCG GTCGCGAGCC
42300


 


CACGCCCGGG TCTGGGAGCC ACCCTGCGGC AGTCGCGCCC TGCGTGGCAC GCTGCTCCCC
42360


 


CAGGGGCGAG GCGCCCCCGC CCGACGTCCC GGTCCCGAGC GCTCCCCGCC GCGGCGCCTC
42420


 


GCAGCCCAGC GCCCCACCAG CCCCGCCGGC GCCGCAGACC CCAGCCTCGG GCGGGTCGGG
42480


 


CCCAGGCTTG CAACGCGCAG GGTAGGAGAA GGGAAATTGG CGTCCGCTGC CGGCCGCTGC
42540


 


CCCAGGCGAG GCCAGACGAG GCCTCTGCTC AGATCCCGCC GCCCCACAAA GCCCGTGGCC
42600


 


CCGGAGCCTA CCGGAAATGG TGCTGGCCAT GGTGCTGGCG GCGGTTGGGC CTGCGGAGGC
42660


 


TGGAGAGGCG CAAGTGGCGG CCGGAGCTGC AGACGGCTGG TGCTGCAGTG CCGGGGAGGG
42720


 


GAGGGGAGAG GAGTGGAGGG AGCGAGGGCG GGCGGGAGGC GGGCGCGGCG GGAGAGAGAG
42780


 


AGGGAGGGAG ACAGAGGGAG AGAGAGAGAG GGTTGGGGGA AGGAGCGGGG GGAGGAGGGA
42840


 


GGGAGGGTTG GGGGAAGGAG AGAGAGAGAG AGAGAGACTG CGGGGGCGGG GGAAGGAGGG
42900


 


AGGGAGGAAG GGAGGGAGGA AGAGAGAGAG GAGCAAGCGC CTGGCTGCGG AAGGGGCCGC
42960


 


GGCTCTCAGG GGGAGAGGGC GGAGGAGGGG GGCTACCCGA ACTGCAACAA GACCCCCCAC
43020


 


CCTCCAACCG CTCACAGCGG GACAGCTGCT TCTCCAACTT GGCTTTGTGA GGCCTGAGAG
43080


 


TGGGGTGGGG GTGGAGATGA GCCCCCATTC CCCAGGGCAG GCGGGGCAGG GGCAATGCCG
43140


 


GAGGAGCAGG TCCCACCCAT GGGGTGGGGC CGCAGAGCTC TTCGCCGCCA AGGCCGCTGT
43200


 


AGGCTGGGCT GGCGCCAACA GGGTCCAGGT CTGTGCCTGC CATCGGAGAG GATGCCACAG
43260


 


CCACAGGGGT GGGCGCTGGC CTGGAGGCCT CCAAGGGGCA TCTCCTGTGA GCCCAGGGGA
43320


 


TGGGCAGGAT CTGAGCGGAG AAGAGTGAAA GTGGAGGAGT GAGGCCAGAA CAAAGGCTTT
43380


 


GCCGTGAAAG AGGTGGTTTC CCGCCTGGGC TCAGACCTTC ACTCACTGTG TGGCCCAGGC
43440


 


CAAGGGCAAG CGTCTGACCT CGCTGGGCCT TTGTTTCTCA GGGGTAAGAT GAAACAATGA
43500


 


TGCCCCCAGA CGATGGAGAG GAGGGGTGCC AGGGTTGTGC GCACTTACTG AGTGGGGGGC
43560


 


AACCTATCCT GCCTCCCCCT CTCCTCATAA CTCCCAAAGG GAAACCCTGG TAGGCAAACG
43620


 


GAGCGTCTTT GCCATTGCAG GGATGAAGCC ACCGAGGCAG GGAGAAAAGT GCTTTGCCCT
43680


 


ACAAGCAACT AAGTCATAGG GCCAGGAGCA AAACCCTGAA AACCTCAGGA GACTTGCAGA
43740


 


GCCATGAGGC TGGCTCAGCA ACACAAAAGC CAGGGGCAAG CCTCAGCTCT AGCAGTGCGG
43800


 


TGGGAGCACC CAAGGCCAGT CACATCCTAG GGTGGCCTGG AGAGTCCTGA CCCCTGACGT
43860


 


GCAAGCCGGC ATCATCCCCG GGACTGTGAG TCTGGTGGGG GTGATGCCCA GGAATGTGAC
43920


 


ATTGTGTGGC CCAGAGGTAC CCTTAAGACT GGAGGATCAC CAGGCGGGCC CTGACCTCAT
43980


 


CACAGGAGCC CTTTAAAAGC AGTTTCCTTT GCCTGGTTGA AGAAATCGGA GGGATCAAAC
44040


 


CAAAGAAGGT TTTCTGTTGT TGAGATGAGG GGGCCACGTG GCAAGGATCT GAGAACTGCT
44100


 


CCCAGCCAAC AGCCAGCAAG ACAACAAGAC CTTAACTGCA AGGAAGTGAG TTCTGCCAAC
44160


 


AAGAAGAGAA TGGGCTTGGA GGCAGGTTTG ACCCCAGGGC CTCCACACAA GAACTGAGCC
44220


 


CAACTGCCCA CTTGGTTTCA GCCTTGGGTT ACTAAGAATT AGGAGGTAAT GAATGAGAGT
44280


 


TGTTTTAAGC TGTTGGTTTT GTGGTGATTT GCTATGAAGC CATATCAAAC TAATATACAC
44340


 


ACAGAGGTGT TGGCCCCTGG GCCATTCCTA GGAAGCCAGC TCTGCGAAGG AGGAAGAAGG
44400


 


GCAGAGAGGC ACACAGAGCT GCCCACCACA GCAGCTGTGT CCTCCCTGTT GGCCACCACA
44460


 


GTAGCAGTTG GGGATGGTCA GCATCCTTCA GGCAGACTCC AGCCCCGGGT GCTGGAGCTC
44520


 


AGGTGCTAGG GATCAAGAGA AGTAGCCCTC TCTGGGACCT CCAGAGTCTT CTCATGTGGG
44580


 


TGGGGTAGGA CCCACCCAGT CAGGCTCAGA GCACCGCAAT GCCTCACACT CATTGTGACT
44640


 


CTGGCCAGGC CCTCTCTGAG CCTCTGTGTC CTCATCTGGA GCACAGGGAC CAGGTGTGTG
44700


 


GAAGCCCGTG GCATAGTGCC AGGAACACAG TAGATGTGCA CAGTGTGCAC TAGCAGGAAC
44760


 


ACACAACAGG GGTACTGACT GTCAGCACCT AGGCAGGCAC ACGCAATGGG CTACTGACTG
44820


 


TCAGCCATAC TGACTGTCAG CGTGCTAGCA GGCATACACA ACAGCTGTAC TGACAGCACA
44880


 


CTAGCAGGCA CATGCCATAG GTGTACTGAC TCTCAGTGCA CTGGCAGGCA CACGCAATAG
44940


 


GAGTAATGAC AGCATGCTGG CAGGCACACA ATAGCTGTAC TGACTGTTTG CCCCAATATA
45000


 


GTGCCAGGTC TTGGAGCAGA TTTTGACTTC TCACCAAGAT CAAATGCAGA AAGTGCACGA
45060


 


GCATTTCAAA GATGTTTTTC ACATGCACAT TAGTGCTAGT TAAAAAAATG TTTTGACTGG
45120


 


GTGCAGTGGC TCACAACTGT AATCCCAACA CTTTGGGGGG CCGAGGTGGG CAGATCACCT
45180


 


GAGGTCAGGA GTTTGAGACC AGCCTGGCCA ACATGGTGAA ACCCCATCTA CCCTAAAAAT
45240


 


ACAAAAATTA GCCAGGTGTG GTGGCAGGTG CCTGTAATCT CAGCTACTTT GGAGGCTGAA
45300


 


GCAGGAGAAT CACTTGAATC CAGGAGGCAG AGGTTGCAGT GAGCCGAGAT CCCACCACTG
45360


 


CACTCCAGCC TGGGCAACAA TATCAAGACT CCACCTCAAA AAAAAAAATG TTTTTCATAA
45420


 


AGTGTGACTT TTATCAGACC TCTGCATTCT TGAAATTAAC TCTGGCTTGG CTGGGCGTGG
45480


 


TGGCCCACAC CTGTAATCTT AACACTTTGG GACGCTGAGG TGGGCAGATC ACGAGGTCAG
45540


 


GAGTTCAAGA CCAGCCTGAC CAACATGATG AAACCCCATC TCTACTAAAA ATACAAAAAT
45600


 


TAGCCGGGCG TGGTGGCATG CACCTGTAAT CCCAGCTACT CAGGAGGCTG AGGCAGGAGA
45660


 


ATCGCTTGAA CCCAGGAGGT GGAGGTTGCA GGGAGCCCAG ATCGCACCAC TCTATTCCAG
45720


 


CCTGGGCGAC AGAGCAAGAC TCTGTCTCAA AAAAAAAAAA GAAAGAAAGA AATTAACTCT
45780


 


GGCTCCTAGA AGGAGCCCTA TATCTCAGCA GGACACTCAG TCATTCAACA GACATCTGTC
45840


 


AAGCACCTGC TGTATGCTGG AGCTGTGGGT ACGTCAGCAA TTAGAGGAAG AGGGCAGGGG
45900


 


TACAGGAGTT CCTGACCACC CCAGGCCAGC ACGCTCCTAT AGCAGCTGGC AAGGAGCAGA
45960


 


TGACTCAGAC TTCAGCTCAG TCCACAGGAC AGCCTTTTCT GGCCACTGCT CTCAGGAGAT
46020


 


GAGATGTGTG GCTGCAAAAG GTAAACTCCT GGCTCCTGAG CAGGCTCTGG GCAATCTGCT
46080


 


CAACGCTCTG TGCCTCACTT TCTCACCCAG AAAGTGTGGA CAATGAGAGG ACTTATCTGG
46140


 


CTGGGCGCGG TGGCTCACGC CTGTAATCCC AGCACTTTGG GAGGCCGAGG CGGGTGGATC
46200


 


ACCTGAGGTC AGGAGTTCAA GACCTGCCTG GCCAACACGG TCAAACTCCA TCTCTACTAA
46260


 


AAATATAAAA AATTAGCCGG GCTTAGTGGT GCACACCTGT AATCCCAGCT ACTTGAGAGG
46320


 


CTGAGGCAGG AGAATCACTT GAACCCAGGA GGTGGAGGTT GCAGTGAGCC AAGATTGTGC
46380


 


CACTGCACTC CAGCCTGGGC AAAAAGCCAA AACTCTGTCT CAAAGAAAAA AGAATCATGG
46440


 


CAGAAGGTGA AGTCTATGTT AGTCCCAGTT CCCAGGTCGT ACATGGCGGC AGGAGAAAGA
46500


 


GAGAGAGAAG GGGAAACTGC CACTTTTAAA CCATCGGGTC TCCTGAGCAC TCACTGTCAG
46560


 


AACAGCCTGG AGGAAACTGA CCGCATGATC CAACCACCTC CCTCCAGGTC CCTCCCTCCA
46620


 


CACGTGGGGA TTACAATTCG AGGTGAGACT TGGGTGGAGA CACAGAGCCG AACCATATCA
46680


 


GCATGTATGG GGGGCACTGA AACTTGTGCT TGGTGCCCAT TCATTCAACG AGTGTGTGTG
46740


 


GCTGGTCTCC TCATCTTCAA CTCCCTGCCG AGTCTCAGAT AGGCAGCCTG CAGTTCCTTC
46800


 


ACCACAACAG GCACATGGGG CTGGGTGCCA GTGAGTGCTG GGGCTTCTCC GAGCACTATC
46860


 


TCACACCCAG GAGCGTGGGC ACGCATGGCA TTCGCATGTG CCGTCAGTGG ACATTAAACA
46920


 


CAGCCATGAA GAAGCCACGA AGAAGTGCTG CCTGCCGGCC GTGCGCGGTC ACGCAGCGCC
46980


 


AACTCCCTCC TGGGGCCTTC TGGGGCCTTC TGGGGCATGG GAGCTGGGGC CGCCTGAGAC
47040


 


AAACATCCGT GACGCTGGGC TGACCCCACA GAACGGTGCG GGCCTCGCTC TTGGAGTCAG
47100


 


CCCTGCTGCC AGCCAGTGCC GGGTGCTGGG GACTCAGGGA GGCCCGCCGG GACCACTGCG
47160


 


GGACAGTGAG CCGAGCAGAA GCTGGAACGC AGGAGAGGAA GGAGAGGGGG CGGTCAGGGC
47220


 


TCTCAGGAGC CGGGTCCTGG GCAAGGCGCA GCCGTTTTCA AATTTTCAGG AAAGCGGTCG
47280


 


GCTCACACTC GAGCAGTAAA AAGATGCCTC TGGGGAGGAG GCCCGTGCAG CTCTCCGGGC
47340


 


AATGGTGGTG GCTCGGCCTA GAGAGGCGGT AGTGGAACGC AGACCCTGGT GGGGGAATGA
47400


 


CATCAAGGGA GGAGACGGGC GGGACCCCAG ATTTCTGCCT GTGGGCGATG GAAGTGAGGT
47460


 


TCACTGGCCA GCGGAGCCGG ACACAGAACG CGCAAAACGC CGTGTAGGCC TGGAGGAGCC
47520


 


GAAGAGCAGG CGGACCCCCT CCGCGGGGGA ACAGTTTCCG CCGGGAGCAC AAAGCAACGG
47580


 


ACCGGAAGTG GGGGGCGGAA GTGCAGTGGG CTCAGCGCCG ACTGCGCGCC TCTGCCCGCG
47640


 


AAAACTCTGA GCTGGCTGAC AGCTGGGGAC GGGTGGCGGC CCTCGACTGG AGTCGGTTGA
47700


 


GTTCCTGAGG GACCCCGGTT CTGGAAGGTT CGCCGCGGAG ACAAGTGAGC AGTGAGTCGC
47760


 


AGTGACCCTA CAAGTGGTTC TTTTACCCGA GCGGCTCGTA GGCGCGTTGC GGTTTTTCGA
47820


 


AACTACAGCT CCCGGCAGGC CCCAAGCCGC CCTCGGGGCC GCGGGTCGGC GGATTGGCCG
47880


 


CGCTGCATTT TGGGACCTGT AGTTTCCTGC GCTCGTGGCG CTGGCGCCGC GGCCTTGGCT
47940


 


GAGCCCTTGA CCGGGGCTGG AGGGAAGGGC CGACATTCAG TGTGTCCGCG TCTGTTCTGT
48000


 


TAGTCCCAGT TCCCGGGCGG GATTGAGGCT TAGAGAAGTT GAGTGATTTG CTGAGGGCTG
48060


 


CACGGGTTGG CATCCCGGCA TGCTCTTTCG CTACTTTGGC TGCATCTGGT TGCCCACCCG
48120


 


GGCGGATGGG GAATGGACTC CAGCCAGCCA GGAGGGCAGA GGGCTGGAGA GGCAGGGCCG
48180


 


GAGGTTCAGA CCCTCCGCTC TGACGTTGCG CCTGGTGAGG CCGGGAGGGG TGCCGCTTGC
48240


 


CTCTTCAGCC CTCACGCTCT TGTGGAAGTC GCGGAATTAC TGCAGGCGGA ACTTGCAGCA
48300


 


CTGTGGGCGT CTTTTCCAGA GAAGGACGGA GTTGTGGGGC GGGAGGATAA GGCAAGGCCC
48360


 


AGCCACTTCG CATCTTCGCC CCGCCAGCTC CTCGAGATGG GATATACCAG GGTTGCTCTC
48420


 


CAACCCTCTC CGCAGGAGGG ACTGATGGAA ACGCCTGGGA AAGTAGCCCG GTACCCACAA
48480


 


AGGCTGTCTA CAAACAGAGT CTTACTGTCT TTCCCAGGTC TGTGCCATAG GGATTCTCGA
48540


 


AGAGAACAGC GTTGTGTCCC AGTGCACATG CTCGCATCGC TTACCAGGAG TGCCCGAGAC
48600


 


CCTAAGATGT TCGGAGTGGT TTTTTCGCAC AGACCCGAAT AGCCTGCCCC TCAGCCACGC
48660


 


TCTGTGCCCT TCTGAGAACA GGCTGATATG CCCAAGATAG TCCTGAATGG TGTGACCGTA
48720


 


GACTTCCCTT TCCAGCCCTA CAAATGCCAA CAGGAGTACA TGACCAAGGT CCTGGAATGT
48780


 


CTGCAGCAGG TAGAGCACAG GCCCCGAGGA AAGGACTGCG GGTGGGTGGA GCTTCAGCCA
48840


 


GGACGGGGTG TGCTTCCCTC TCCCGGCCCA TTCCAGCCAG GCCCCTCCGG GCCAGAGGCA
48900


 


GCGTCTGTCA TAAAAAGGGC TGGTGTTCCA GGTGGGGTCA GAGAGAGGAT TGACAAGTAA
48960


 


AAACGATCGT CCTTTGAAGG GGGCCGGCCC CTCCACACCT GTGGGTATTT CTCATCAGGC
49020


 


GGGACGAGAG ACTGAGAAAA TGAATAAGAC ACAGAGACAA AGTATAGAGA GAAAAGTGGG
49080


 


CCCAGGGGAC CGGCGCTCAG CATACAGAGG ACCTGCACCG GCACCAGTCT CTGAGTTTCC
49140


 


TCAGTATTCA TTAATTACTA TTTTCACTAT CTCAGCAAGA GGAATGCGGC AGGACAGCAA
49200


 


GGTGATAGTG GGGAGAAGGT CAGCAAGAAA ACGTGAGCAA AGGAATCTGG GTCACAAATA
49260


 


AGTTCAAGGG AAGGTACTAT GCCTGGATGT GCACGTAGGC TAGTTTTATG CTTTTCTCCA
49320


 


CCCAAACATC TCGGTGGAGT AAAGAGTAAC AGAGCAGCAT TGCTGCCAAT ATGTCTCGCC
49380


 


TCCTGCCACA GGGCGGCTTT TCTCCTATCT CAGAATTGAA CAAATGTACA ATCGGGTTTT
49440


 


ATACCGAAAC ATTCAGTTCC CAGGGGCAGG CAGGAGACAG TGGCCTTCCT CTATCTCGAC
49500


 


TGCAAGAGGC TTTCCTCTTT TACTAATCCT CACCACAGAC CCTTCACGGG TGTTGGGCTG
49560


 


GGGGACTGTC AGGTCTTTCC CATCCCACGA GGCCATATTT CAGACTATCA CATGGAGAGA
49620


 


AACCTTGCGC AATACCCGGC TTTCCAGGGC AGAGGTCCCT GCGGCTTTCC GCAGTGCATC
49680


 


GTGCCCCTGG TTTATCGAGA CTGGAGAATG GCGATGACTT TTACCAAGCA TACTGCCTGT
49740


 


AAACATATTG TTAACAAGGC ATGTTCTGCA CAGCTCTAGA TCCCTTAAAC CTTGATTCCA
49800


 


TACAACACAT GTTTCTGTGA GCTCAAGGCT GGGGCAAAGT TACAGATTAA CAGCATCTTA
49860


 


GGGCAAAGCA ATTGTTCAGG GTACAGGTCA AAATGGAGTG TGTTATGTCT TCCCTTTCTA
49920


 


CATAGACACA GTAACAGTCT GATCTCTCTT TTCCCTACAG TCCTTGAGGG TGACAGACTT
49980


 


AGGAGTGCCT TGGGGGCCTC TCTGAGGAGC AGCTGATATT CACGGGTCAG GAGGAACCAT
50040


 


TTCCATTAGA GGGGCAGCCG GTGGCCAGCC TCACTTGGAA GGTCTTTGAA CCTCGGGGGT
50100


 


GCAGGGAGGT GGCAGTGGTG CAGGTTGCCT TCTCCTGGGT TCCTTGAGGT GCCCTCTTGT
50160


 


ACCCGGCTCA CACCCTTCCC CTCCCCGAGT TTCCTGCTCA GGTTCCCGTC TGAGAGCTTG
50220


 


TATGTAGGAC GTCAGATAGG ACAGCATAAA TGTTTGGATC CAGAAACGCA GAACAGTTTC
50280


 


CTATTTTGAG ACTTGACACC TAATTAGTCA TCTTACTATT TAAGCTGAAA AATAGTGTCG
50340


 


TGTTTTGGGT AACGTTCTGC AAATCGTTTG CTAATGGCGG CTGAGTTGCT TCACGCCCTT
50400


 


TAGGGCAAGA GTGGGACTTG CCTGTGGACT TCTCCGCGGT CCCACAGGGC TCTCGCCACC
50460


 


TGGCAGTGGC CTCTGCATCT GCAAAGAGCT GCCCGCTGGC TGCCGAAGCT TGTCTCAGGG
50520


 


CAGCTTGTGT GGCCTCGCCT CTTCCTGGCT TCCCCGTAAC CCTTGCTCCG AACTCCGTTC
50580


 


AGAAGGTGAA TGGCATCCTG GAGAGCCCTA CGGGTACAGG GAAGACGCTG TGCCTGCTGT
50640


 


GCACCACGCT GGCCTGGCGA GAACACCTCC GAGACGGCAT CTCTGCCCGC AAGATTGCCG
50700


 


AGAGGGCGCA AGGAGAGCTT TTCCCGGATC GGGCCTTGTC ATCCTGGGGC AACGCTGCTG
50760


 


CTGCTGCTGG AGACCCCATA GGTGACCCTA GTTCCCAGGC CTCTCCTGGC CTCCTGTGGG
50820


 


GATGGTTGGC AAGGGATGGC GCTGAGGGTG GGGTGGGCCC ATGGGGACTC CTGCCGTCTC
50880


 


TCAAGCAGAA CTCAAGGAGA ATTTTTTAGC TGCTGTATAA TTTCTCGCCA TCGTGGGTGT
50940


 


AAACCTAGGG TTGGGCTTTT TTGCTGAATT AGGGCACGGC AGATGCCCAC TTCACCCATT
51000


 


TTTGATAAAC CAGTATCTGG GGTGTCAGAT TCTTGGCTGT CTGCAGGGCC GAGTTAGCCG
51060


 


AATGCCACCT GCCTTTGATA CGTGAGAACG TTGTCTGAGA ACCGTGACTT CTGTGCTTGC
51120


 


TTGTGTCTGG TCAGCTTGCT ACACGGACAT CCCAAAGATT ATTTACGCCT CCAGGACCCA
51180


 


CTCGCAACTC ACACAGGTCA TCAACGAGCT TCGGAACACC TCCTACCGGT GGGTCAGACG
51240


 


AGTTTACACC TGTCTCGGGG TCCTCAAGAG AACCAGCTTG GCATGGTGCT GAGTCCACAG
51300


 


CCCCATGCTG TGCTGTGGTG GAGGGTGGTG GTCTTTCTAG ACGCTCCCCC GAAGTGTGCA
51360


 


GAGCGCTGGT GCCCAGGGGT GGGGTGCGGC CTGGGCTGCC TCCAATGCCC ATTACTTGTG
51420


 


AGGAAGCAGC TTTGCATCTG TGTGCTGACC TTGGGCGGGC GTCCTGAGCT CCTCGCAGGT
51480


 


GCTGTTGTAG CAGCTGTGCA GTAGGTCAGG GCTGGCCCCC AGTGCAGCTT TGCACATGAA
51540


 


GTAGGAGGAG GCCCTGCTGC TTGTCAGAGC CCAGCAGAGT CTTGGTGTTC TGTCGGGTTC
51600


 


CTGTGGCCGG ACCAGTGGCA GGGTGCTGTG GAAGCTGTCG AATCTCCTCC CTCTGTCCAG
51660


 


TACCCCCGCT CGTCTTCTAG CTCCCTCCTA CGCCCGGGCC ACGTTTCAGT TATGCTCACT
51720


 


TCCTCTGACC GCCGAGGCTC CTGCCTGTCT CCATACAGCT CACGCTGCAG GGCCACGCTG
51780


 


TGGGTGTTGG AGACAGCTCC TCCTCGACCC ACGGTGCTCT CTCCCACCAG GCCTAAGGTG
51840


 


TGTGTGCTGG GCTCCCGGGA GCAGCTGTGC ATCCATCCTG AGGTGAAGAA ACAAGAGAGT
51900


 


AACCATCTAC AGGTAGGCTC CTGGGCTCCC GCTCCGGCTC AGTGTCCGAC AGGCGAGTGC
51960


 


TGCTGGGTGT CCAGAGCCCC AGGCTGCCCT CCCGCTGGGC TAGGGTTTGA AGTTCACTGG
52020


 


GGGACTGCAG GGGAGGACCT GGTGGGGGTG GGGACTGGCT TCGGTCCTTT CTTGGCCGTG
52080


 


CTTCAGCTGC GCACTCTGCC CTTCCTCCCA CAGATCCACT TGTGCCGTAA GAAGGTGGCA
52140


 


AGTCGCTCCT GTCATTTCTA CAACAACGTA GAAGGTACAA GCAGCTGGGT GGGACCAGGG
52200


 


TCGGGTTGGA GTGTGTGCAG CCTCTCAGGG TGGAGCTCAG TGGTGTCACA GCCTGGTTGT
52260


 


GCTTGCCCGG TGGGGCGGCC AGTGCGGCCA TGTACCTGGG CCCTGTCTTC TGACTCGGGG
52320


 


CCACCCATGT TAGACTTCTG TGTGGAAGAG CTCACACAGT GGTCTGAGAC AGCCAGCCGG
52380


 


CAAGACTGCC TCTGGCTGGT GCCTGGGGCC TTGGATTTTG GGAAGGCTCC CTCCATTTCC
52440


 


TGATGAGAGG GTCTCCCTGC ACCTAACCTG CTGGTGCAAA CAGTAGGGGT TTTGCTGAAC
52500


 


ACCGGCTTTC TCTTCGGGGA CTTTGTTGCT TGCCCAGCAG CAGGTGCTCC AGTGACCGGC
52560


 


CCTCATACCA TCTTGGGAGG GTGTCCTGGA AGCCGTGTCT GGCCTCCCGC GACCCTGCCC
52620


 


CGTGTGTCTT TTTCCTGTGC TGACCTTGCT GCGGAAAATT ATGGCCCTGA GTGTGACTCC
52680


 


AGGCTGAGTC CTGTGGGTCC AACACGGGAT GCCTTGGGGC CTCTTCTGGA GACGGGATGT
52740


 


GAGTGACAGG AGCCGGCCGG GGCAGCTTGC CCTGTGACTG CACGTGGCCA CAGCCTGTGA
52800


 


GGGCCGGGGG TGCTTCTCCA CCCACGTGGC TGCCCCTCGG GTATGTCAAG GCCTTCTGGG
52860


 


GCTCATCACG GGGTCCTAGA GACAGTGGCA GGGTGCACCC CCGTTGGCTG CCCTTACAGT
52920


 


TTCTGTGACC TGAGGGTGGC ATCTGTGCAG TCGGCGCGGT CTGTGCTTCT GTGGGATCAG
52980


 


GGTTCCCTCT GTTTCCTGCC TCAGTTGGGG CTCAAGCCTC AGGTGAGGTG GCCCCGGAGC
53040


 


ACTCAGAAGG CATCGGCGGT CCTGTGGGCT GCTTTCTGCA CTCACGTTTG CTGAGTGCTC
53100


 


AGTGTGCCAG GACTGAGGAC CCTGAAGCTG CTCTTGTATT TAGGGCGGCG CTCCCCTGGC
53160


 


AGAGACTGAG CCAGGTGGTC CCGCATGACC CACTACCAGG CGTTTCTGGG CCCTGGCCCT
53220


 


TGGAGGGACA GGGTGGGCGG AACATGGGCC TGCAGGGAGG CTCCCGCTTA CTGGAGGCAT
53280


 


GTGCTGTGTT GCTGGAGACA TCCTCTGTGT TGCTTCTTGT TCGCTGTGGT TTTTGGTCTG
53340


 


GTGGCACCAA GGACCCTCAG TCATCTTGAT GTGTGGTTGT CCAGGCCTTT TTGTTGGTCC
53400


 


TAAGAAGGGG CTCTGCCTTT GTGCCCCCAG GTTCCCTGAC AGGAGCTGCC GGCTCGTCCC
53460


 


GGTGATGCCT GCAGGACGTG ACTCTGGGAC GGGGGGTTGG GCAGATGTGC TGATGGAAAT
53520


 


TCTCAACCAG GCGTCATTTC CGAGGTCCTC ACCTGGATTT CCAGGACAGG AGTGCCTGCT
53580


 


GGGTGTCCCC AGTCCCATGC AGCGGGGGTC CTTGGGATAG CATGGAACGC TGAGCATGGG
53640


 


CCTGGCCGGC CGTGGTCCTG GACAAGGGCA GTGCCCCGGT GGCTGCTGGG CCTGGGACCT
53700


 


GGTGGGGACG CTGGGCCTGG TACCTGGTGG GGATGCTGGG CCTGGGACCT GGTGGGGAGG
53760


 


CCTCTGACTG CCTCCTGGTG CTGCTTCCGT CTGTGTTAGG CCTCTGGGTA TTGGGGCCCC
53820


 


CATCTGTCTC CTCCTCCAGG CCTGTGGACT CAGACCAGGA AGACACAGGC CAGCCCCTGC
53880


 


CTGTCCCCCT TGGCTTGGGC TCTCACTGCC CGACCTGGCG GGAGGTTGCC TAGCCGTGAA
53940


 


CCTTCGCACC CTGTCTGCCA CCGGACAGGC TGTGAGGGGG TGTCTGCAGC ACCTGCACCG
54000


 


GCCTGAGCAT CTTCAGAGTG GGCTGCAGCT CCTGGAGGGG TCTGAGAGGA AGGGAGGCAG
54060


 


GTATTTTGGG CGAATGAGGA GACAGCTGGA GAGCTGGCAC CCTTCCTGGC CTGCGTCCTG
54120


 


TGAGGACTCT GGTTGGGGAC AGCAAGCTTG GGGTCAGCCT GGGGCAGAGC CTCTGGGACG
54180


 


GCCCCGCCCC TCGTGCCCCT TCCCCTCGCA GCTCCTGTCC TCGCCCCGCC CTCAGCTCTC
54240


 


CGCCAGGCAA GGTTTGGCAA GTGCCGCTGT GCGGCAGTGC CTGCTGATTG GCTGGTCTGT
54300


 


TGCTATGGTG CTGCCCAGGG GTGTGCTTTT CCTCCCCTGC CTTCCCTGCT ATCCCTGGGA
54360


 


GTATCTGGGG TTGGGTCATC GCTGGTGTGT GTGAGTGTGT GTGTGTGTGT ATGTGCACGT
54420


 


GTGCATATGT GTGCGCTTCT GGCCTCTGCA GCTGAGTCCT GGCCCTCGGG GGGCCTGGCA
54480


 


CCTCCTGGGG ACAGGCACAA AGCAGCCATG ATGGAGTCGG GAGCTGGGGG AGGCCCCATT
54540


 


GCCCCACGTG GCTGCCCTGT GACTCTGGGG TGCTTGTTAG AAGAGGTATC TGGTTCTGTC
54600


 


TGTGTTTAAG CAACTCCCTA AGGAATTCTT GTGGTTCCAG TTTGGGGGGC CTGTACTGTA
54660


 


GAGGCAAGGG AGGGGCAGGA CATCCCCCAG ACTCTGACTT CTGAAGCCTT TTCTGCCCGG
54720


 


GGCCTCTCCG CCAGTACAGG CAGTGTCCTT TGCCAGGGCT GCCATGCTGC AGAGGGGAGT
54780


 


GGGCCACTGT TTAGCCCAGG AAAACCTGGC TCTCCCTTAG CTGGAAGTTC TGGGCCTGTT
54840


 


GTGGTTGGCA GGGAAGCTGA GTGACGGTGC TAATCACAGG GGCACCTGCA GGGGTTTGTG
54900


 


GGAGATGCCT CTGTGGGTTG GGGCGATAGG CTGAGGGGCT GTTCTTCCCT GCCCTGAGGA
54960


 


GGGCTGAGTG TAGCCGCCAC TCCTGTCCTG TCTTGGGCTG TCTCGGAGAG GATGCGTAGA
55020


 


ACCCTCGGGA TCCTGCTGGC CTCCGTCTGG TCCACCCTGA ACCTCAGGCC TTCTGGGGGC
55080


 


AGAGGAGGAT TCCCTCAGGA TCACTCGGGT GGGGGCCTCT CTTGGGCACC TGAGACCCTC
55140


 


AGTGGGTGCT TTGTGGCGCG TTCACGGTTG GTGGGGGACG CCCAGCCCTG CCCGCCGTGT
55200


 


AGGAGCCGTT CTGTCCTGGG CATCCCCCTG TGGTCTGGGA CTTAGTGGAC CCTGAGGGTG
55260


 


TGTGTTTACC CCTGCCTCAC ACCTGCAGAA AAAAGCCTGG AGCAGGAGCT GGCCAGCCCC
55320


 


ATCCTGGACA TTGAGGACTT GGTCAAGAGC GGAAGCAAGC ACAGGTGAGA CCCCTCAGTG
55380


 


AGGCCACGAC CACTGTCCTT CCATGGCCCA GCTCTCCTGT GACCTGTGGA GGCCCGGATA
55440


 


TATTTCTTCA CTTTTCTTTG TTCCTTTTTA AATTATGAAA CTAACCACCA TTCAGTACGA
55500


 


AAAAGTTTAA GCAGCTCTGA GGAAGATAGA GTAAAAAATT GTCTCCCTCT TCCCTGGCCC
55560


 


TCAGCCATCC CCGGTGGCCA CCGTGGAGTG TGGACGGAGC CCTGCAGGCC TGTGTCTGTG
55620


 


CGGAAGCACG CGCAGTTTTG TCTGCACAGA CTGTCCTGCA GTTGGCTGTT TTCACTCAGC
55680


 


GTTGTGGGTA TAGCTTCCCA TGCTGGTGCT GGCAGCTCGG CCTTGTTCTT TTGAGGACAG
55740


 


CAGATGTCTC CTATGTCTAC CTCTTACAGC TTCAGAGATT CAAGTTATAA TAAAGCTCTT
55800


 


CTTATATTGA GGGGGAAACC TCCCTCCCCC TTTTTTTTGA AACAGGGTCT CGCTCTGCTA
55860


 


CCCAGGCTGC AGTGCAGTGT CACAGTCTTG GCTCACTCCA GCCTCAGCCT CCCAGGCTCA
55920


 


AGCGATTTTC CCACCTCAGC CTCCCAAGTA GCCGGGACTG CAGGCACGCA CCACCATGCC
55980


 


TGGTTAATTT TTGTATTTTT TGTACAGACA GGGTCTCACT CTGTTGCTCA GGCCAGTCTC
56040


 


CTCAGCTCGA GAGTTCCACC TGCCTTGGCC TCCCAAAGTG CTGGGATTAC AGGCGTGAGA
56100


 


CCCCATGCCT GGCCAGCTCT TTTTTTTTTT TTTTTTTTTT TTGAGACGGA GTCTCGCTCT
56160


 


GTCGCCCAGG CTGGAGTGCA GTGGTGCGAT CTCGGCTCAC TGCAAGCTCC GCCTCCCGAG
56220


 


TTCACGCCAT TCTCCTGCCT CAGCCTCCCG AGTAGCTGGG ACTACAGGTG CCCGCCACCA
56280


 


CGTCTGGCTA ATTTTCTGTA TTTTTAGTAG AGACGGGGTT TCACCGTGTT AGCCAGGATG
56340


 


GTCTCGATCT TCTGACCTTG TGATCCGCCC ACCTCGGCCT CCCAAAGTGC TGGGATTACA
56400


 


GGAGTGAGCC ACCGCGCCCG GCCCAGCTCT GCTTTTTCTT AGTGGTTCTG CCTTGTGTTT
56460


 


GTTTCTATCC AGGAATAGGG TTGGTTTTAC TTTTCCATCG AGTTTTTAAA GAGACGACGA
56520


 


TTTACATGGT CGGAAACTCA CGAGGACTCC CCATCCCTTG GTCGGAAACT CACATGGACT
56580


 


CCCCATCCCT TGGTCAGAAA CTCACGTGGA CTCCCATCCA TCCCACGCAG CAGCTTCCCA
56640


 


CCTGGGCCCT ACGTGCAGGA TGAGGGCTCC TTCCGGGTCA GAAGACATGG CGGCCTCGGG
56700


 


GCACCGTCCC CTGCATGGGG TGCTCACAGG ATCTTCTCCT CTCTCCTTCC CAGGGTGTGC
56760


 


CCTTACTACC TGTCCCGGAA CCTGAAGCAG CAAGCCGACA TCATATTCAT GCCGTACAAT
56820


 


TACTTGTTGG ATGCCAAGGT GGGGGCTCAG TCCTGTAGCT GACGACTCCT GATGTCCAGG
56880


 


GGTGTCCCTG GGCTTGGGAA CAGCTGTCCG AGCCTTTGCT GCTTCAGGGC CTTAGATCAG
56940


 


CAGGCCTGGG TGGGAGGACT CACCTCTGTC ACTGGGCAGG GGCTCAACCT GGCCAGACAC
57000


 


ACTTGTGAGC AGCCCCAGGC CACAGGTCAG TTTTCTGAGC AGTCTGGGAG CGGGCAGGCT
57060


 


GGTGGGAGTG AGGAGAGACC TCCAGGCTGT GGTCCATAGG CCAGTGCCCG CTCTTGATCC
57120


 


TGACAGCTCA GGTTCTCTCC TTCACGTCAG GCCATGGGAG GCACCGAGAA CACAGGAAGC
57180


 


CCACTGACTC CCCTCTTCCC AGCGCGTGCC CGGCCCCACA CTCACTCCCC CTCCCAGCAT
57240


 


GTGCCCGGCT TCACACTCAC TCCCCTCTTC CCAGTGCATG CCCGGCCCCA CACTCACTCC
57300


 


CCCCACAGCA TGTGCCCGGC CTGACACTCA CTCCCCTCCT CCCAGTGTGT GCCCAGCCCC
57360


 


ACTCCCTTCC GCCCCGTGTG CCCAGCCCCA CGCTCACTCC CCCCGCCAGC ATGTGCCCGG
57420


 


CCCCACACTC AACTCCCCTC CTCCCAGTGT GTGCCCGGCC CTGCTGCCCT CCTCCCCATG
57480


 


TGCCCTGCTT TTGTGCCCCA CACTTTTTAC TTAGTGCAGG TGGGATCACA CGCCACGGGT
57540


 


CAATGGTTTG TGTGTTCACG TGACGATGGC GTGGTGACGT TTCCAGATCC CGTCGTTGGT
57600


 


TCGCTCATTC TCGGGGTGTA TATTTATTGA GAGCTCATCA TGCTGGGTGC TATTCCAGGC
57660


 


ATAGCAAGAC TGGCTTCACT CACATGGAGC TTTGATTCTA GTGGTGGGGA CAGGTGGACA
57720


 


GCAAAAGAGT AAGCACGTGA GCTGACGATA CTGAAGGGAA ATAGAGCAGA GGGAGGAGGC
57780


 


GGAGACCGAG CCAAGCGGGC CCAAGTGCGA TGTCGGCGGG AGGTGGGGAA TGCTGGTGGG
57840


 


TCTGAGGGGA GCCTCAGCAG GTGCAGCAGA GCAAGGGAAG AGGTGAGTGG GGGCGGCTGG
57900


 


GGGGCCGACT CCTGGGAAGC TGTAGCAGAA CCCCACAGAG AGCTGGTGAG GTTTGCCGTG
57960


 


GTTGTGGGTG ACTCGGTGCT TTGAGCCCTG GCTGCCCCTG GGAACCATCT GGAGAGCTTC
58020


 


TAACCCAACC AGGCCCCTCC CTGGGACAGT TATATCACAG CTGGTAAGCC GAGTCTAACA
58080


 


CTTTCACGGA AACGCAGAAC ATCTAAAACA GCAAGATGAC CGTGAAGAAG AACAGAGCTG
58140


 


GAGGACTCAC CTCGCTGGTT TCAAGACTCC TCTAAAGCTG CAGGAGTGGA GGTGGAGATG
58200


 


GCCCAGCTCA GGCACAGGCC TGCAGGCCAT GGAGAAGGCA GCAAGCTCAA GCTGACCCAC
58260


 


ACGCATGTGG TCATTGTTTT TTTTTTCAGT TGGAATCTCA CTCTGTCACC CAGGTTGGAG
58320


 


TGCAGTGGCA CCATCTCGGC TCACTGCAGC CCCCGCCCCT AGGTTCTAGC GATTCTCCCA
58380


 


CATCAGCCTC CCGAGTAGCT GGGATTACAG GCGTGCGCCA CCATGCCTGG CCCTTGGTGA
58440


 


TTGTTTTTTG ACAAACATGC CAATTTAATT GAGAGAGGAA ATGAAGGTTG ATTTCTGGTT
58500


 


TTCTGAAAAA ATGGTGCTAA GAACAGCTGG ATATCTGTTC GGAAAACAGT GAATCTTAAC
58560


 


TCTTGTTTTA CCCTGTATAA ACCTAAATGT AAAAGCTAAA CTAAAAGTTA TAGAAAGGAA
58620


 


CATGGGGGAG GTCTTTGCAA CTTTGGGGTA GGCAGAGATT TCTTAGTATG GATACACAAG
58680


 


GCACTAGCCA TGAAGAAAAA CATTAAAATT TAGACTTCAC CAAAATTTAA AGCTTCAACT
58740


 


CTGTGGAAGA GTTGAGAAAA TGAAAAAGCA GTTAAAGAAA GGGAGAAAAT ACTTCTTTCA
58800


 


AAGGACTTAA AAAATTTTTT CAGCCCTCCT CTGATTTGAA AGGACCTTTG ACCAGAGTAT
58860


 


GTAAAATTCT CCCATAACTA AGCAAACAAC CCACTTAACC ACTGGGAAGG GATCTGGACA
58920


 


GACGTTTCAC CAAGATGGGT GGAATGGCCA GTTAACCACT GGGAGAGCAT CCGGACAGAC
58980


 


GTTTCGCCAA GATGGGTGGA ATGGCCAGTT AACCACTGGG AGAGCATCCG GACAGACGTT
59040


 


TCGCCAAGAT GGGTGGAATG GCCAGTTAAC CACTGGGAGA GCATCCGGAC AGACGTTTCG
59100


 


CCAAGATGGG TGGAATGGCC AGTTAACCAC TGGGAGAGCA TCCGGACAGA CGTTTCGCCA
59160


 


AGATGGGTGG AATGGCCAGT TAACCACTGG GAGAGCATCC GGACAGACGT TTCGCCAAGA
59220


 


TGGGTGGAAT GGCCAGTTAA CCACTGGGAG AGCATCCGGA CAGACGTTTC GCCAAGATGG
59280


 


GTGGAATGGC CAGTTAACCA CTGGGAGAGC ATCCGGACAG ACGTTTCGCC AAGATGGGTG
59340


 


GAATGGCCAG TTAACCACTG GGAGAGCATC CGGACAGACG TTTCGCCAAG ATGGGTGGAA
59400


 


TGGCCAGTTA ACCACTGGGA GAGCATCCGG ACACACGTTT CGCCAAGATG GGTGGAATGG
59460


 


CCAGTTAACC ACTGGGAGAG CATCCGGACA GACGTTTCGC CAAGATGGGT GGAATGGCCA
59520


 


GTTAACCACT GGGAGAGCAT CCGGACAGAC GTTTCACCAA GGTGGATGCA ATGACCAGTT
59580


 


GAGCACATGG AAAGTCGCCC AGCATCTCCA GTCATAGGAG AAGGCAGATT AAAGCCACGG
59640


 


GGAGCCGACA CTGTGGTCCC ACTGGCATGG CTGAAATTCA GAAGCCCTGA GTGTGGCATG
59700


 


AGGATGTGGA ACAGCTGGAT CTCATCCATC GCTGTGAAGT TGTCTAGCCA CTCCACAAAC
59760


 


GTGTGGCAAA CAGCCGAGCC GGGAGAAGGG AAGACGTGTT CAAAGATTCA TATGTGGCCA
59820


 


GGCTCAGTGG CTCACGCCTG TAATCCCAGA ACTTTAGGGG CCAAGGCTGG GGGATCGCTT
59880


 


AAGCCCAGGA GTTTGAGACC AGCCTAGGCA ACATACGGAG ACCCCATCTC AAAAAAAAAA
59940


 


AAAAAGAAAA AAGAAAAGAC TTCAGTGTGC AGGTTTACCA GAGTTTTGTT TGCAGTTGCC
60000


 


AAAACTGGGA AGCAGCCCGC GTGAGCCCAT CCACAGGTGA ATGGACAGAC CGTGGTACCC
60060


 


GAACACTAAC AGCAGCCACG GGCGTGGACT GTGGTCACAC AGCAGCAGGG AGCCGATGAG
60120


 


TCTCGGACAT GCTAACCCAG AGAGGCCCAT TGAGGAGGAC CTACTGTTTT TTGTGTTTTT
60180


 


GTTTTTTGTT TTGAAATGGA GTCTCGCTCT GTGGTGCAGG CTGGAGTGCA GTGGTGTGGT
60240


 


CTTGGCTCAC TGCAGCTTCC GCCTCTTGGG TTCAAACAGT TCTCCTGCCT CAGCCTTCCG
60300


 


AGTAGCTGGG ACTACAGGCA CCCGCCACCA CACCCGGCTA ATTTTTGTAT TTTCAGTAGA
60360


 


GACGGCAGTT CGCCATGTTG GCCAGGCTGG TCCCAAACTC CTGACCTTGT CATCCACTCA
60420


 


CTTTGGCCTC CCAAAGTGCT GAGGTTGCAG GCATGAACCA CCGCACCCGG CTGGACCTAC
60480


 


TGTTTTATTC CATTTATGTG ACACTCTATT AATAGAAAAG GCAGGGGTGG GGCTGGTGGT
60540


 


TATATGGTGC ACATAACTGC CAGAACTCAG TACACTTAAA ATGAACATCT TAATGTGTGA
60600


 


AATTTTTTTT TTTGAGACGG GGTCTTGCTC TGTCACCCAG GCTAGAGTGC AGTGGTGCGA
60660


 


TCTCCACTCA CTGCAAGCTC TGCCTCCTGG GTTCACGCCA TTCTCCTGCC TCAGCCTCCC
60720


 


GAGTAGCTGG GACTACAGGC GCCCGCCACC ACGCCTGGCT AATTTTTTTT TTTTTTTTGT
60780


 


ATTTTTAGTA GAGACGGGGT TTCACAGTGT TCGCCAGGCT GGTCTCGATC TCCTGACCTC
60840


 


GTGATCCGCC TGCCTCGGCC TCCGAAAGTG CTGGGCTTGC AGGCGTGAGC CACCATGCCC
60900


 


GGCCAATGTG TGAAAATTTA AAAGTACCAA AGCTGGACCC CACCCCAGAT TGCTCCCATG
60960


 


ACACTCTGTG GGTGGGACCT GGGAGTTGGG TTTTGTTTTG TTTTGTTTTG TTTTTGAGAT
61020


 


GAAGTCTCAC TCTGTCGCCT AGGCTGGAGT GCAGTGACAC AATCTCGGCT CACATTAACC
61080


 


TCTGCCTCCC AGATGAAAGC GATTCTCCTG CCTCAGCCTT CTGAGTAGCT GGGATTACAG
61140


 


GCACACACCA CCACCCCCTG CTAATTTTTG TATTTTTAGT AGAGACGGGG TTTTACCATG
61200


 


TTGGCCAGGC TGGTCTTGAA CTCCTGACCT CGTCATCCGC CCGCCTCGGC CTCCCAAAGT
61260


 


GCTGGGATTA CAGGCGTGAG CCACCGCGCC TGGCTGGGAG TTGGGTTTGT AAATCTCCCT
61320


 


GAGTGGGGCT GGGGCAGGGA ACTGCTGGGT CTGGGTCTTC CTGGCTCCTC TGGTCTGTGG
61380


 


CTTCCTGACT GCGGTGGCCG GGGGCTCCCA GGGCATCGTG GCCGTCTGTC TTGCTGAGCG
61440


 


TGGCACGTGC CTTTCCATGC TGTGGAGGAG CGTCTCCCGG TATGGCGAAC TGCTGGTTAG
61500


 


GGTGGGGCGG TGTTGCCAGG TCATCCAGGT CTGGCCTCTG CTCTCGACAT CGCCGGCGCT
61560


 


GTTGCTCATC TGCGCTTGTG ATGTTCGATG CCTGCTGCAC ATGTCTTGGC TTCCCTCTTT
61620


 


CCCGGCCTCT GTGAGCTCCA GCGCTGCGTC CCTTCTCTTC CTCCTGTAGA GCCGCAGAGC
61680


 


ACACAACATT GACCTGAAGG GGACAGTCGT GATCTTTGAC GAAGCTCACA ACGTGGTGAG
61740


 


TCTCCGCTGG CCTCCTAAAC ACCTCCTATT GCTTCTGGCC TTTTTGTCAA GAGCCACGCA
61800


 


AACCTTTCTG GAGGGGCTCT GGCCAAACTC CTGAAGCCCT AGGTGCCCAG GACTGGGGAC
61860


 


TGAGCACACC AGGAGCTTCT GCCACCCCCT CCCGCCCTGA TCCGATGCCT CTGCTGGGGC
61920


 


TGGAGACTGG CCAGCTGGGC CAGGGACCTG CCCGTCAGGC GCAGGGCCCC CACAGGCCGC
61980


 


TCACCAGACC CTTTCCCTCC AGCCAGCTCG GGGTCAGCCT GGGCCAGGGC TGTCTCCTCT
62040


 


GCCCTCGGCA GCAGCAGGCT TGTGGTCTTG CCTGCAGTGT CTCTGCCCTT CCGGCCACAT
62100


 


GGCTTGAGAC TGAGGCAGGA GAATCGCTTG AACCTTGGAG GCAGAGGCTG CAGTGAGCCA
62160


 


GGATCACACC ACTGCATTCC AGCCTGGGTG ACAAAGCGGG ATTCTGTGTC AAAAAAAAAA
62220


 


ATGTTGACTG GGCGCGCTAG CTCATGCCTA TAATCCCAGC ACTTTGGGAG GCTGAGGTGG
62280


 


GCGGATCACG AGGTCAAGAG ATCAAGACCA TCCTGGCCAA CATAGTGAAA CACCGTCTCT
62340


 


ACTAAAAATA CAAAAAAATT AGCTGGGCGT GGTGGCGTGT GCCTATAGTC CCAGCTACTC
62400


 


AGGAGGCTGA GGCAGGAGAA TCACTCGAAC CCAGGAGGTA GAGGTTGCAA TGAGCCAAGA
62460


 


TCACACCACT GTACTCCAGC CTGGTGACAG AGCAAGACTC CGTCTCAAAA AAAATAAAAT
62520


 


CAAAAAGAAT AATTGGCAAT TCCAGTGAAA TAATTGTTTG TTTGTTTGTT GAGACAGGGT
62580


 


CTCCTTCTGT CGTCCAGGCT GGAGTTCAGT GGTATGATCT TGGCCCACTG CAACCTCCAC
62640


 


CTCCTGGGCT CAAGCCATCC TCCCACCTCA GCCTCCCGAG TAGCCGGGAC TACAGGTGCA
62700


 


CACCACCACG CCCGGCTAAT TTTTGTATTT TTTGTAGAGG CGGGGTTTCC CAGCGTTGCC
62760


 


CAGGCTGGTC TTGAACCCCT GAGCTCAAGT GATCTGCCCA CCTTGGCCTC CCAAAGTGCT
62820


 


GGGATTACAG GTGTGAGCCA CCGCGCCCGG CCTGAAACAA TCGTTTCTAA ATATTGGTGT
62880


 


GGGCCACACA GTCATGTTTG GACCTACTTG TGGCCTTTTA CAGACCCCAG GCCAAGGCTT
62940


 


TGGGAACTTG GCTGTCAGCC TCCTGTGCCT TCTGCACCCC CACCCCATTT CTGCTTTCTG
63000


 


GAACCCCCGA TCCTGTCCTG TTCTGTGGTG ATTCGGGTGT GCTTGGGCTC TAGGAGAAGA
63060


 


TGTGTGAAGA ATCGGCATCC TTTGACCTGA CTCCCCATGA CCTGGCTTCA GGACTGGACG
63120


 


TCATAGACCA GGTGCTGGAG GAGCAGACCA AGGCAGCGCA GCAGGGTGAG CCCCACCCGG
63180


 


AGTTCAGCGC GGACTCCCCC AGCCCAGGTG CGTTCATAGC CAGACTGCTT GGTCCTGAGG
63240


 


CCTGCGCTGC TGCAGGGTGA GCCCCACCCG GAGTTCAGCA CGGACTCCCC CAGCCCAGGT
63300


 


GCGTTCATAG CCAGGCTGCT TGGTCCTGAG GCCCGTGCTA CTGCAGTGGG CAGCCTGCCC
63360


 


TGTGGCTGTG TGTGGTCGGC CTGGGCACCA TCTATTCAGG CTGGCACTGC AGGGCATCCG
63420


 


CTTCTCTCAG AGGCTTCTTG GGTGTGAATT CTTCAGGCTC CTGTAGCCTG TGGAAGGGCT
63480


 


GGTATTGTTC AGTAGTTCTG GTATTTTCCA AAGACCTATG TCTTCTCCCA GCCAGTATCA
63540


 


ACTTGGCCTC TACTGTGTAA AACTGGAAAA CTCTACTTTG TGAAGCTGAG TTGGGAGCAT
63600


 


CGCTTGAGGC CAGGAGTTTG AGACCAGCCT GGGCAACATG GCGGAACCTC GCCCCTGCCA
63660


 


AAAAATTAGC CAGGTGTGGT GGTGTGCTCC TGTGGTCCAA GCTTTTCTGG AGGCCGAAGT
63720


 


GGGAGGCGTG CTTGAGCCTG GGAGGCAGAG CTTCCGGTGC CCCAGATGAC TCCACTGCAC
63780


 


TCCAGCCTGG GCGGCAGAGT GAGGCCATCT CAAAAAAAAA AAAAAGGAAA ACTAAATATA
63840


 


TTCACTCTAA GGGCATTTTG CATCTTTAAA TGACCCACAA ATCTGGCATG CATCAGCTGC
63900


 


TCTGCCTGTA GGTTCCTTCC CAGTGTTTGT CCAGAGGTGT ATTTCCACAC AGCGCTAGTC
63960


 


ACGGCATATG TGGAAAACGT GGAAACCCTT CATGGATGTT GTCAGTTGCT CTATATTTTC
64020


 


TTTCTTTTTT TTTTTTTTGA GATGGAGTTT CACTTTTGTT GCCCAGGCTG GAGTGCAATG
64080


 


GCGCGATCTT GGCTCACTGC AACCTCCGCC TCCTGGGTTC AAGCAATTCT CCTGCCTCAG
64140


 


CCTCCCAAGT AGCTGGGATC ACAGGCGTGC ACCACCACGC CCAGCTAATT TTGTATTTTT
64200


 


AGTAGAGATG GTTTCTCCGT GTTGGCCAGG CTGGTCTCGA ACTCCTGACC TCACGTGATC
64260


 


CACCCGCTTC GGCCTCCCAA AGTGCTGGGA TTACAGGCGT GAGCCGCCAC GCCCGGCCTT
64320


 


TGTCCATATT TTCTACATGG CTTCTGTAAA CAGCTGACTA GGAGTCTGTG TGAATATCTT
64380


 


CATAGGTTCT GCTGTGACAC TACTTGCTCG TGAGCATCTC CAGGTGTAAA CAGCATCAGC
64440


 


TTCCCCCATT TTCCTTTAAA ATCGCACATG TGGACGGACA CCACGGGGAC CCTGGACCCT
64500


 


GGGGAGCCCC GTCCTCACCC TTCTCACCAG GATGGCTGCT TGGTAGAGAG TGAGTTTGCA
64560


 


AAGTTGGCAT TTGTTTAGTA CAGAAGTTAT CAGGTGTTCT GGCTTTAGAA TCCCTTTATA
64620


 


TATATATATA TATACATATA TTTAAGTGAC AGGGTCTCAC TCTGTTGCCC AGGCTGGAAT
64680


 


GTGGTGGTAC AATCAAAGTT CCCTGTAGCC TCGGCCTCCT GGGCTCATGG GATCTTCCCG
64740


 


TCTCAGCGTC TTAAAGCGCC GGGACCACAG GTGTGCACCA CTGCCACCGG CTCTCAAGAT
64800


 


TGCCACGCAG GGAGTTGCAG TGGGGGAAGG GGTTCCTGGG ACTTTGAACG CTCCACCTCC
64860


 


CTCCTCTCCA CAGTCCCCCA ACCCCACCTC TCTAACGGGG TGGACGGCCG CCTCTTTCCA
64920


 


TCCTTCGCTT GGCGCAGGGT GGGGAGAGTG ACAGGTCTCC TTCCCTCATC TCGGCAGCTG
64980


 


CCATTTCATC GCTTACATAA CGTGGGAGAA ACATCCACCC ACCCCCAGGC CTGTGTGAAC
65040


 


ATCACCACGG GGCCTTCTCC ACTCTTCAGT TTTGTTAGTT ACTTGATGTG CAGGGCTTTT
65100


 


TGTTGTAACT AGTGGGGGAC GTGTGGTGGG GTGGGCTTCT GCCATCTCAT TCAGGACCAG
65160


 


AACTTCAGTT TTCATCCCTA TCTGTTCCCC CACCCCTTTG GAGATGGGGT CTCACTCTGT
65220


 


CACCCAGGCT GGAGAGCGGT GGTGCCATCA CGGCTCACTG CAGCCTCCAC CTCCTGCAGC
65280


 


CTCCACCTCT TGGGCTCAAG TGATCCTCCT GCCTCGGCCT CCCAAGCTCC TGGGACTACA
65340


 


GGCGTGTGCC ACTGTGCTTG GCAGGGTCCA TTCTTTTCCT CACACTTTAT TTATTGAAGA
65400


 


GCCCAGGCCG TTTACCCTGC AGAGTCGGAA TCTGTACAGG AGGGGCAGCC ACACGAGTTC
65460


 


CCCGGTTTAC TCTGAACTTA GGTGGCTTGA GGGCCCCAGT TAGACTGCGG CCACCGTTTG
65520


 


CCGGGCTCCA GATGGGACGT CCTTTCTATC AGAAGGCTCA CAGTATCTCC TTTCCCGTTT
65580


 


CTTCCCATGT GAACATTGTT GCTGCTGAAC ACCTGAATAT GTTAATCACT GGGGGCTTGC
65640


 


AAGATGGCAG TGTGCTAATT CCATCATCTA GTCAGTTAGC AGGAATAACT TAGGACCACG
65700


 


CCCTGCACCA TATCAGCTAT GTGGTGATCC CATTCACACA GGAAAGGTGG GACAAATGCT
65760


 


GGGGGTGGGC CGGGTGTGCT GTCTCACACC TGTCATCCCA GCACTTTGGG AGGCCCAGGC
65820


 


AGGCGGATCA CGAGGTCAGA GATTGAGACC ATCCTGGCCA ACACGGTGAA ACCCCGTCTC
65880


 


TACTAAAAAT ACAAAAAAAT TAGCCAGGTG TGGTGGTGCA TGCTTGTAAT CCCAGCTACT
65940


 


TGGGAGGCTG AGGCAGGAGA ATCACTTGAA CCCAGGAGGC GGAGGTTGCA GTGAGCCGAG
66000


 


ATCGCACCAT TGCACTCCAG CCTGGCAACA GAGCGAGACT CCGTCTCAAA AATCAATCAG
66060


 


TCAATCAAGT GTCATCACTG AATGTTTGTG TGTGAACGTG GGGATTGGTC CTGCCCCATG
66120


 


CTCCCTCCTG AATCTCACTC CTGACCTCAG TTGCTGCACC TTGAGGTGTT TTCTGTGGGC
66180


 


TCTTGTGTCC TGACCCCGGC GGTTGTGGCC TCTGCTGTCT GGGAGTCAGG ATTTTTCACA
66240


 


CTCATGTCCT GCTCCAGACC TGGAATCAGC CAAGTCTCCA AGAAGCCCTG CTTTCTTTTC
66300


 


CTGCAAGACG GTATTTCAAG ACCCGCCGTG CGGCAGCGGG TTGGTCATGG TTACTGGGTT
66360


 


GGTCGTTGTG ACTGGGTGTT TTCGTGGAGA TACAGCCATA CGCACAGGTG TGTTCACAAA
66420


 


TGTTAATTCT AAAGGTCAAA CACCCGGCCA GGCATAAGGG CTCAGCGGTA ATCCCAGCAC
66480


 


TTTGGGAGAC CAAGACTGGT GGATCACCTG AGGTCAGGAG TTTAAGACCA GCCTGAGCAA
66540


 


CAGGGTGAAA CCCCATCTCT ACTAAAAATG CGAAAATTAG CCGGGCATGG TGGCGCACAC
66600


 


CTATAGTCCC AGCTAGTCGG GAGACAGACA CGAGAATTGC TTGAACCTGG GACATGGAGG
66660


 


TTGCAGTGAG CAGAGATGGC GCTGCTGCAC CCCTGCCTGG GTGACAGAGT GACACCCTGT
66720


 


CTCAAAAATG AATAGATAAA TAAAGATAAA ACACCTGCTC CTCTTGGTGT CTCCAGTTTG
66780


 


GATTTGGCCT GTGTAGCCTC TTCCTTCGCC TGTTGGTGGA TTTGGCCTGC ACGGATTCTG
66840


 


TGTGGCCTCT TCCTTCCCCT GTTGGTGGAT TTGGCCTGCA CGGATTCTGT GTGGCCTCTT
66900


 


CCTTCCCCTG TTGGTGGATT TGGCCTGCAC GGATTCTGTG TGGCCTCTTC CTTCCCCTGT
66960


 


TGGTGGATTT GGCCTGCACG GATTCTGTGT GGCCTCTTCC TTCCCCTGTT GGTGGATTTG
67020


 


GCCTGCACGG ATTCTGTGTG GCCTCTTCCT TCCCCTGTTG GTGGATTTGG CCTGCACGGA
67080


 


TTCTGTGTGG CCTCTTCCTT CCCATGTTGG TGGATTTGGC CTGCATGGAT TCTGTGTGGC
67140


 


CTCTTCCTTT CCATGTTGGT GTCCTTTTTT CCATGCCAGG AATCCTGGTT CTCAAGGGCG
67200


 


GGGTTGTTGG CACGAGCGTG ATGCAGACTG CCTTTGCTGC CTTTCTCTTG CCCAGGGCTG
67260


 


AACATGGAGC TGGAAGACAT TGCAAAGCTG AAGAGTAAGT GTTGCCCTCC CCGCCTCCTT
67320


 


GCAGCTGGGT GGGGCCTCCT CCTTGCGAGG AGGTGGGTGA CACCTCCTCG ACCCACAGTG
67380


 


ATCCTGCTGC GCCTGGAGGG GGCCATCGAT GCTGTTGAGC TGCCTGGAGA CGACAGCGGT
67440


 


GTCACCAAGC CAGGGAGGTG AGAGGCGGGG AGCCAGCCCC TTCACTGCAG GCCCAGCCTA
67500


 


GAGCTAGAAA CGGGCCATGG TGCAGTCCTG GGCTGTCACA TCACGAGTGA GGCCTGTTTT
67560


 


CAGGCCTGTT TTCCCTTTTT GAGACCTGGG AGGAGCACCT GCTTTGCATG ATCTGGTTGC
67620


 


TGAGATGTTG AGAGGAGCAG CACACACTCC CACGGGACAG CACACAGCCC CCCACGGAAC
67680


 


GGCACACACA CCCATGGAAC AGCACACACA CTCCCACGAA CAGCACACAC ACTCCCACGA
67740


 


ACAGCACACA CACTCCCACG GAACAGCACA CACACCCACG GAACGGCACA CACACCCACG
67800


 


GAACAGCACA CACACTCCCA CGGAACAGCA CACACACCCA CGGAACGGCA CACACTCCCA
67860


 


CGGAACAGCA CACTCTCCCA CGGAACAGCA CACTCTCCCA CGGAACAGCA CACACACTCC
67920


 


CACGGAACAG CACACACACC CACGGAACGG CACACACTCC CACGGAACAG CAGACTCTCC
67980


 


CACGGAACAG CACACACACT CCCACAGACA GCACACACAC ACCCACGGAA CAGCACACTC
68040


 


TCCCACGCGG GGCCGCTGGG TTTCCTGCAG TTTCTCCTCC TCCAGGCCTT TCCCTGGACC
68100


 


CTGGTCCACT CCGTCATTTG AGCACAGGTG CCTGTTAGAA CGAGACCTTC TTGTTAGGAC
68160


 


GATGAGTGTC CCACCCACCA CCTCTTTTGG ACTCCGGGAG GCCTGGAACG TTCTGAACGC
68220


 


TCCGTGGGGC TCCAGTCTTC TCCGCAGCCA GGGCAGCAGG GTTTGCTGTC TGTCCTGCAG
68280


 


GCAGATGAGG AGTCAGGGCT GGGGCCTGTG TGGGGGCTCT CCTGAGCGCG CAGCCGCCGA
68340


 


GGTGGAGCGT GTTCTGCCTG AGCGCCGACC TGGTCGGGGG AATCCCAGTT GCTTCCAGGT
68400


 


GGAGCCACTG TCCTCAGCGT AATGCTCAAG GCTCTGGCCT GGCTCCTCGG CCACCCTGCA
68460


 


CCCTCAGGGT CCCCTCCTGT AGCTTCTGCT GCCCCATCAC TGTCACTCTC CAAAGCTTTG
68520


 


GGGACTCTGC CCAGAGCCAC CGCCTCCCAG AAGCCCCTGA CAACCTCTTG ACGACCCCCT
68580


 


AGTGACCCCA TCCCTCCCCT CTGACGGCGG CCCCTGCTCT GAGGCGGCTT CTTTTCCTCG
68640


 


GTGCTGTTCT CGTGCTGGCC AGGCCTCCTC TCCCCACCTG GAGGCTCCTG AGGGCGGAGG
68700


 


CCTCTCACCT CCAATGCTGG CGTCCCCTGG AGGGCTGAAT TTGTTTCCGA GGGAAGGAAA
68760


 


CTTCCACAGT TGTTGCCTTC AGTTCCAAAG CTGCAGCCTG ATTTCCCCCT CCAGGCTCGA
68820


 


GCCTGTTTTC TTCTCGGCAG CTACATCTTT GACCAGTGTC GTCCCCCCTC AGGCCCGAGC
68880


 


CTGCCTTCTT CTCCTCAGTT CCCAAAGCTG CAGTCTGGTC CCCCCGCCAG GCTCGAGCCT
68940


 


GCCTTCTTCT CCTCGGCAGC TACATCTTTG AGCTGTTTGC TGAAGCCCAG ATCACGTTTC
69000


 


AGACCAAGGG CTGCATCCTG GACTCGCTGG ACCAGATCAT CCAGCACCTG GCAGGACGTG
69060


 


AGTGCTGGCA CGGGGTCTTT GGTGCGGGCA AATGTGGCGT AGGGGGTGCA GCAGGCCTCC
69120


 


ATCTTGGCAG TCAGGGCTCC CCTGGCCGTC ACCTGGCCGT CAGCAGGAAC AGGCCCACAG
69180


 


AACCTCATCT TCTGATCGGG GCGTGGAGGC GTTAGTGCCA CTTGCCAGCT GCCGTAGAGC
69240


 


CTGTCCCAGT TCTGCAGCTG GCGGCTTCGT CCTACAGCCT CATCCCATTA TTCTGCTTTT
69300


 


GAGAAAGAGC AGCCCAAGGC CCTAGCTGGC TTGTGGGGCC TCTGGCTTCT CCACACCACC
69360


 


CCGAGTTCTG CTTCTCAGAG TTGTGGGGTC CAGAGGCTTT GCCCAGAGGC GGTCTCCCCA
69420


 


TGGGCTGCTC TGGTTTGAGA CGCCGGGCCC AGCGGGGTCT CTCCTCTGCT GCGCTCCCGG
69480


 


GTGCTGGGGA GGGTGGCTTT TGCTGCTTCA ACCCTTAGGC GACCATAGAG CCTCTTTTCA
69540


 


AGTCCCACTG ACCCCCTTGG AGACTCTGTC CCTGCCTGGC TTCTCTCCTG GCTGCTGGGA
69600


 


AGAGCAGGCG AACTGCCCGC CCTGAATGGA TGCTGCGCTC CACCCTGGGC CCCCCATTGG
69660


 


GCAGGAGATG GAGCTTGGCA GTCGGGCTGA GCGGGCTCAT GCTGGAAGGG CCGGGGCTGG
69720


 


GGTCGGGGCC TCCCCTGCCT GCAGTGTGGG TGTCAGCGCC CTGCTGCCCT CCAGGTGCTG
69780


 


GAGTGTTCAC CAACACGGCC GGACTGCAGA AGCTGGCGGA CATTATCCAG GTGGGGCCTG
69840


 


CTCCTCTGTG GCATCTCCTT CCCTGATGGA AGCCGGGCGG GTGCCTTCTC CTGCTGTATT
69900


 


AGTTAACTGA TTCTAGACTT GGGGATGGGA GAAAGGCCCC TACACCACCT GTTTCTGATT
69960


 


GGCAAACTCT CGGCTCCTTT CCAGTGCCCT AAACCCACAC TGGGCCTCCT GCAGGGATGG
70020


 


GGGAGGACGA GGTCTGGTGG CACATGCCCA GGGTGATGCT GGTGAGGGAG GACGCAAAGG
70080


 


ACAGTGGGGG CCGGGGAGCC GCTCCTGCCC TGTCCGGGCC CTCAGGCCAG GGGGGACCCA
70140


 


CTGCTGGCAG CCCCAGCAGC CCCAGCTGCA CGCAGATGAA GAGCTCTGGA CACACGCGGC
70200


 


TTCCTGAACA GCTTCTCCAG GGACAGACAA ATGGGGACCC TGCAGGTTCC CGGCAGGGGT
70260


 


GTCCCTGGGA GCCCATGATT GGGGGTGCGA CCCTGGCCCC CTTCTCATTG GCCCCGTCCT
70320


 


GTCCTGCAAT GCCCGTCCCA TGTGAGGTCT GCTTCTGGCT CCATGCCTAT GGCAGCACCT
70380


 


GCTTTCCCTG GCGTAGAGGT GCTTGTCCGG TTTGTGGAGG GCACGCCCCA TTTTGGGTGC
70440


 


TCTGGGCACG TTGCCTCTCC GGGGCCTCGG TGGCTTTTTT AGAAGCAGAC TCAGAAGTCC
70500


 


CTGACTGGGG AAGCCAAGGC ACAGGTGGCT GTGTGGAGCC CTGTGAGCCC TCCTCTGTGC
70560


 


TGCCCACGCT GTACCTGCTG GCCACACGAG ATCATGGCAG GGTTAGGCAG GGCTGCCCAG
70620


 


CGCTATGACA GCTTCATGAG TGTCCATCTG GCCTGTGGGG TGCTTGAGCT GGGGGAGGCC
70680


 


GCAGAAGAAC CCTGGGATGC ATGGCTGGCC TGTGCATGCT GCTGGGCATG GAGCTGCAGA
70740


 


TCCCGGAACA AGCAGGCACT GCCTTCTCCT TCACAGACGC AGCTCTGAGC GGGGGCGAGA
70800


 


CCTGGGCAGG GACCAGGTGG GGTGGGCACA GGGTGGTGGG GCCCAGGCTC AGCCCTCCCT
70860


 


CCACTGTGGC CGTCTCTGTG GCCAGTGACG CCACAGCCTG TGTCTTCTCT GTGCGGTAGC
70920


 


TGGGGCTGGA AGGACAGCAC TGCCTTGTCC TCCCAACTCC TCCCCAAAGG CACGGTGGGC
70980


 


ATCCCAGGCC CAGACCCCTC TGTCTGTGGC TCCTGCCTGC CAAGGGCTGC TGTGCTGTCC
71040


 


CGCATGGAGT GTGGTTGGCT CTTCAAGCAG GAGGCCGTGC ACCTATCAGG CGGACCTGCT
71100


 


TCCATGTCCC TGATGGGTCA CTGCAAAGCA CCTCCAGCAC ATGGCCAGGC GAGGTAGCCC
71160


 


TGCAGCCCAG GGCCTGGAGG GCAGGTGTGA GCTGGCCCGG GCCTGTCCCT CCCTGGAATA
71220


 


CAGCTTCCCA GGCTCCCACT TATGGAGAAG TCTCCTCCAC ACTATGGAAC TGAATCCTAG
71280


 


AATGTGGCTT CTGAGGTTCC TACACTCGAA CTGAATCCTG GAATGCGGCT TCCAAGGCTT
71340


 


CCAGCTATGG AGAAGACTCC ACACTCTGGA ACCGAATCCT GGAACGCGGC CTCCCAGGCC
71400


 


CCCAGCTATG GAGAAGACTC CACACTCTGG AACCGAATCC TGGAACGCGG CCTCCCAGGC
71460


 


CCCCAGCTAT GGAGAAGACT CCACACTCTG GAACCGGATC CTGGAACGCG GCCTCCCAGC
71520


 


CTCCCACTTA AGGAGAAGTC TCCACACTCT GGAACCGGAT CCTGGAACGT GGCCTCCCAG
71580


 


GCCCCCACTT AAGGAGAAGA CTCCACACTC TGGAACCGAA TCCTGCACAC TCCATCGGTT
71640


 


TGGAATTTCC TTTGGCTGCT GCTCTAAGTA GCCGCTGGTG GATGACTCAG CTTCTGCCAG
71700


 


CCCTCGGGTG CCTGGAGGAT GAGGGACTGC ACACAGTGCT CACCCGCGTT GGCTCCTGAG
71760


 


CCCCTGCAGG TGTGGGCGGT GCCCATAGGG CTGGTGCTGG GTTGGGCCTG CAGCCCTGAG
71820


 


TCACAGGTGA CCCTGGGGGC AGAGTGGGGC CAGTGGCCCC AGGAAGAGGA TGTGGGATGC
71880


 


ACAGCTCAGC TGGAGGCGAA CTCCAGGCAG GGTCAGGCCG TGTGCTCGGA AGTCAGGGCT
71940


 


TAGCTGGAGG CAAACTCTGG GCAGTGCTGG CCCGTGTTCG GGAACCAGTT GCCCCTGGGC
72000


 


CCCCGTGAGA CTGCTGGGTC CTCATCCCTC TCTGCCTGAG GCCGGAGCTG CCCTGGGCTG
72060


 


AGGCACAGGG GGATTTGTGG TGCTGTTTTT TTGAGAAAGG GTCTCGCTTT GTCACCCCGG
72120


 


CTGGAGTGCA GGGGCTTGAT CACAGCTCAC TGCAGCCTCA ACCTCCTGGG CCCAAGTGAT
72180


 


CCTCTTGCCT CAGCCACCCG AGGAGCTGTG AACACAGGTG TGCACCACCG CACTCAGCTA
72240


 


ATTTTTAAAA TTTTTTTGTA GAGATGAGGT CTTGCCATGT TTCCCAGGCT GGTCTCAAAC
72300


 


TCCTGGGCTC AGGCAGTCTG CCCGCCTTGG CCTCCCAAAG TGCTGGGATT ACAGGCAAGA
72360


 


GCTTCCATGC CTGCCCAGCA GAAGGCTTTT CGAAGGAAGC TGTTTCCTGA GGCAGACTCA
72420


 


GCCCTGCTCA TGGCAGCCAC CAGCGTGGGG GTGAACTTCT TCTGTTACTT CCATCCCCGT
72480


 


GGGCCAAATG CTTTGGTAAA ACACAAGGCC CTGTGTTTAG CTGTCTTGAC AGTGAAAATG
72540


 


GCTGGGAAGG AAGGAAGGAA CGGAAGGAAA TTTCTCTCTC CTTCTGTGCG TACCCAGGCA
72600


 


CGTGCACATG CATGCAGAGT ACGCACACAC GCACGCACGC CTGCACAAAT CCACGCATGT
72660


 


TGCCAAGTCT CTGTGTTCCA GCCGTGGTGT CTGCCCCCCG GTGTTCTCTA GTTCGGCTTC
72720


 


TCCGCATTTC TGTGAATGAT TCCGGCTTCT TGGTGTTCCC AGCAGAACTC CCTCAAGTCT
72780


 


GCGGCGGGGC TCTGACGGCG GTGGCTTGGC TGACATGGCC ACATTGCTGA GCCTGTTGGG
72840


 


GGCTTTGCGT TCCTGTTCTG GCCGTTTTTG GCTCGTTTTC CAGGAACGGT CGTCACGCGC
72900


 


TCCTCTCCTA GTGCAGGCAT CATTCCTTTC CCATTGATTT GCAGGGTTCT CTGTAAGTTC
72960


 


TGAGGATCCC ATATACATAT ACTCTCTGTA AGTTCTGAGG ATCCCATATA CATATTCTCT
73020


 


CTCTAAGTTC TGAGGATCCC ATATACATAT TCTCTCTCTA AGTTCTGAGG ATCCCATGCC
73080


 


GACATACATA TTCTTTCCTT GTCTCATGCT GGTCATTTTT TCCATTTTCA TGACAGGTTT
73140


 


GGTGAACACA TGTTTCCTTG TCAGATTTTT GTTCTGAGCT TGTGCCTCCC GACCAAGATG
73200


 


CTAAACCGGG TCTTGTGTAT TCTCCAAACT GCACTGTAGA GTGACGGAGC TTTGTGTCTG
73260


 


GGCCTCCATG CCTTCTGACG TCACCTGTGG GGGTGTGAAA GGCAGACTCT ACCTTGATTT
73320


 


TTCCCAGCAC GCCACACCGG TGGTTCTGTG CGCTGACCGA GCGGCTCGGC TTCCCCCAAC
73380


 


TCCACTGGGC ACCTGCCACA CTTTTCCTCA TGTTTTTGTT CACTGTGGTT TTGTCGTAAG
73440


 


TCCTGGTGTT GGCCTGAACC AATTTCTTTT TGTTTGTTTT TGAGACAGAG TTTTGCTCTT
73500


 


GTTGCCCAGG CTGGAGTGCA GTGGCGCGAT CTCGGCTCAC TGCAAGCTCC GCCTCCCGGG
73560


 


TTCACGCCAT TCTCCTGCCT CAGCCTCCCA AATACCTGGG ATTATAGGCA CCTGCCACCA
73620


 


CGCCTGGCTA ATTTTTTGTA TTTTTAGTAG AGACGAGGTT TCACCGTGTT AGCCAGGATG
73680


 


GTCTCGATCT CCTGACCTCG TGATCCGCCT CCCAAAGTGC TGGGATTACA GGCATGAGCC
73740


 


ACCGTGCCCA GCCTGATATT TTTAGTAGAA ATGGGGTTTT GCCATGTTGG CCAGGCTGGT
73800


 


CTCGAACTCC TGACCTCAGG TGATCCTCTC ACCTTGGCCT CCCAGAGTGC TGGGATTACG
73860


 


GGTGTGAGCC ACCACGCCCG GCCTCTTGTT CTTTTGAAAC CTGCCCTGAC GTTTTTTCCA
73920


 


TAGTGCATCT TGGAGTCAGC GTGTCTACTT CCTGTAAAAA TCTTACTGTG ATTTTGACTA
73980


 


GAATGTGTTG AATTCCTGTT TTTTTTTTGA GTCAGGGTCT CTCTGTTGCC CAGGCTGGAG
74040


 


TGCAGTGGGA CCATCACAGC TCACTGCAGC CTCAACCTCC TGGGCTCAGG GGATCCTCTC
74100


 


AGCTCAACCT CCCAAGTAGC TGGGACCACA GGCACATGCC ACCATGCCCG GCTAGGTTTT
74160


 


TTTTTTTTTT TTTTTGGTGA ACACCCTGGG GTTGCACCAT GTTGCCCACG CTGGTCTCGA
74220


 


ACTCCTGGGT TCGGGCAGTT TGCTCCTCTC AGCCTCCCGG AGTGCTGGGA TTACAGGCCT
74280


 


GAGCCACTGC ACTAGGCCAT GTTGAATTTC TAGATTAATT TGGGGCCCTC AGGGGCACAG
74340


 


AGAGGAGGGC TGGGCCAGTT GGCGGGAGGA GAGGCCCCTC GGGCTGCCGC ATTTTCAGTG
74400


 


CATGGAGATG GCCTATGTTG GGGGAACACA GAGCTCACCG GGGGTCCCTG CAGGGAGGAG
74460


 


AAAGGGTCAG GCAGGTGCCA GCTCCTGTCC ATTGGCCTGG GGCTGCATGA TGGCAGGGGC
74520


 


CGGTGAACCG ATGACCCCTG GGTGTCCTGT GACCTTCTGT GTATGCGGCT GATGCTGCAG
74580


 


AAAGTCGGGT GGCCTCAGGC TCCTGACGGG GCTGCACTTC CTCTGCCTTT CAGATTGTGT
74640


 


TCAGTGTGGA CCCCTCCGAG GGCAGCCCTG GTTCCCCAGC AGGGCTGGGG GCCTTACAGT
74700


 


CCTATAAGGT AGGGGCCACC TCCAGGAGGC AGGTGGAGGG CAGCCCTTGT TCCCCGGCAG
74760


 


GGCTGGGGGC CTTACAGTCC TATAAGGTGG GGGCCACCTC CAGGAGGCAG GTGGGGCTGG
74820


 


GGCTCTTCTG GTCCTAAAAG GTAAGGGGCT GCCCCCAGGA CATGGGCGGG GCCTCCACAC
74880


 


TCCTGGTCCT GTCCCCTCCA GGTGCACATC CATCCTGATG CTGGTCACCG GAGGACGGCT
74940


 


CAGCGGTCTG ATGCCTGGAG CACCACTGCA GCCAGAAAGC GAGGTACAGA CCTGGGCCCA
75000


 


CACGCTCCCC GCCCGCCCGG GTGCAGTGCC CGGCACCACC ATGCCACAGG CTAGGCACAT
75060


 


GCCCAGCCGT GGATCTCCTG CCCCCATGGG CCTGGCCACC TTCTCCATAT CCAGGCCAAT
75120


 


CCAGAGCATT CTCCTCACTG TCCCTCTGAA GATTGGAGTT ACTGAGAGAC GTAGGAGATG
75180


 


GCCTGATGGC ACCGTGACCT GCCCAGAGTC ACCTGGTTGG TGGTGGCAGA GCCACAGCCC
75240


 


AGCCAGGCCT CCCTGCTGGG ACACGCTCGT TTATGCCGAG GCCGTCAGCA CAGAGCCTCC
75300


 


ACAGTGAGGC ACGGCTCTGC CTGCTGCCTC CACGCAGCGC CTGGCCGGGC CAAGCCTCAG
75360


 


GGTCACATCT GAAGGGGGCC CGGCTGGCCC TGTTGTCCGA AGCCCCTGGT GCGCTCAGCC
75420


 


CCGAGGCCCC ACGTGCCTTC TTGGCTTCCT GTCCTCCGTG GCGTCTTCGA GTCGGTGCTG
75480


 


CCGGGGACGC TGTGTGGATG GGGTCTGTGA GTGTGCCCTC GGCTCCGTGT CCGGAGCCCT
75540


 


GTGGTTCTTG GGGTGTATCT GGCCCCACCC CCACTGCGTG GTGTCCAGGG TGGGGCTTCA
75600


 


CGGCTGCAGC TGCGGGAGCT GCTGCCCCTG CCTTGTGCTC CAGTGGGGCC TTGCCTCTGG
75660


 


GCTTGGTTCG TCCCTCTCTG GAACATTCTT TCTCAGCTGC TGTCCGACCC ATGGTGGCAT
75720


 


GACGTGGCCC TGGCTGAAGC AGCCCTTGTG CGGTTGCTGT GGTTGGGTCT GCCTGGCCGA
75780


 


GCCGGAAGGG AAGGGCTGGG AGGGCGTCAG GGTGGCGTGG CTTGACCCCC GCTCGGTGAT
75840


 


GGTCCTGCAG CAAGGCCTCT CCCAGCAGGA AGCGTCCATC CCGGGGGGAG GCCGGCGCCC
75900


 


CTCACGCAGT TGGGGTTGCG GGAGGCAGTG CGTGCCTGAG GCAGCCGGTG CACAGATTCC
75960


 


AAGGGCCTGG AATCTGTTTG TTCCATTGAC CTCTGATGTC ACTTGACTTC TCAGAAGCAG
76020


 


CCACTCCCTG CACTGGGCGT TTGTAGGAAA TGAGCTCCTG GAGGAGGGGG TGGGGAAGTT
76080


 


CCCCCATTGC AGGGCACACT CAGCCCCAGG AAGGAAACGT GCCTCGTCCC TGCTGACTCC
76140


 


GAATCGCAGT CAGAGTCGTT CTGCTTGTGC CGTGTTGAAT TCCCGGCATC CGGCATCCAG
76200


 


ACTCAGCCTC CTCCCCAGGC CACGGCCGCC GTGGCCAGTC GGTCAAGCCC TTCTAGGAAC
76260


 


TTCCTTTGAG CTGGCGCCCT TGTTCACTGC TGACGCCACT CAGAGGCTTG TGCACGTGTC
76320


 


CTGCTTCCAG GCAGAGCTGG GAACTCGCAC CCCGTCTTCT GCACGCGGCC GTGGAATGTC
76380


 


GGGATGCCGG CGCTTCCTTC CCCTGTGCTC TTGGCGGGGT GGGCTTCTTG CCCTGAGCCG
76440


 


CATGTCACAG TTTCTGCAGA AGTTTAGGGT TGGAGTGGGC TGACCTCTCT GCAGGTGTCC
76500


 


CCAGCCTCTG CCTGGGGTCT GCCTCCTACT CCCAGGACCC CCTGTCCCCC AGAGGGGCCC
76560


 


CAAGCTGGCA GGCTCACACT CAGGGCAGCC TCCTTTGTTC TGACTTCTGC ACAGTGGGCC
76620


 


TGGGTGGCTG CCCGCGGCTC GCTTGCTTGA TGCCAGTGGG TGGAGAGGGT GATGGGCAGA
76680


 


GAGGCAGGTG GTCAGGCCCC CAGTCCCGTC CTCACACTCT GTGCCCTCTG CCGCCCCCCG
76740


 


CCCCACAGGG AAGGTGCTGA GCTACTGGTG CTTCAGTCCC GGCCACACCA TGCACGAGCT
76800


 


GGTCCGCCAG GGCGTCCGCT CCCTCATCCT TACCAGCGGC ACGCTGGCCC CGGTGTCCTC
76860


 


CTTTGCTCTG GAGATGCAGA TGTACGGGCC ACCCCTGCCA GGGCCTGAGC ACCGGTGACA
76920


 


CCTCTGACAT CAGCGGGGTG GAAGTGGTGG GGGTCCCCAT GAGCCGGGTG CTGGGGGTCT
76980


 


CGGGCCTCGA GGGCTAAAGG GGTGCTGGTG CACTTCCCCA CTGTCTGCTC CCTCTGGCCA
77040


 


CGCTCAGCCC TTTCCCAGTC TGCCTGGAGA ACCCACACAT CATCGACAAG CACCAGATCT
77100


 


GGGTGGGGGT CGTCCCCAGA GGCCCCGATG GAGCCCAGTT GAGCTCCGCG TTTGACAGAC
77160


 


GGTGAGGGCC TGTCCCTGGG CCCTGCTGGG GTGGGAGGTG GGGGAGCACT GAGGCCTGAG
77220


 


GCCCTGAGCA GTGGCCTCTC CGGCTCTAGG TTTTCCGAGG AGTGCTTATC CTCCCTGGGG
77280


 


AAGGCTCTGG GTGAGTGCCC TGAATGCCCC AGCTGTGCGC ATCCTGGATC CTGGACCCCT
77340


 


GCTCCCAAGA GCTGGTAGGG ACCCCTGCAG ACATCCTGCC CCTGCCTTGA CCCCGGCCCC
77400


 


TGCACTTCCA GGCAACATCG CCCGCGTGGT GCCCTATGGG CTCCTGATCT TCTTCCCTTC
77460


 


CTATCCTGTC ATGGAGAAGA GCCTGGAGTT CTGGCGGGTG CGTCTCCCCT GTGTTCTGGG
77520


 


CGGGGTGGGT GAGGGCAGGG CTGGAGCATG AAGCAGGCAG TGGTCACAGC TCCTGCTTGC
77580


 


CCTCATCGGA TCGGCGGCGT GACCAGGGCT GCCGTGTCCC TGCCTCTTCC TCCCACAGGC
77640


 


CCGCGACTTG GCCAGGAAGA TGGAGGCGCT GAAGCCGCTG TTTGTGGAGC CCAGGAGCAA
77700


 


AGGCAGCTTC TCCGAGGTCG GCACTTGGCC GGGGCTCTGG GCCTGCTGCC CCCTCGTGCC
77760


 


TCCCCTGCCT CTCACAGCTT CCCCAAGGCT GACCACTGGC CCTGACCATG GGCTCCGGCG
77820


 


GCTCCCGCTG CCTCTTCAGG GCTCCTGCGT TTCCTTCCTG GCCCTGAGTG TTGCCTCTTA
77880


 


TCTTACAAAG CCCCCAGCAC CGGGTGGGTG TGGTAACAGT GGCCCTCCTC TCTGAGTAGC
77940


 


CCTAGTCGGC CACCCTGGCC CTGGGGTTCC CCGTGTTTTC TGGGAAGCAC TGAGCAGGCG
78000


 


TGGGGTCAGC CTGGGATCCG TGCCAGGAAG AAGCTTCCAG AACCCGATTG GCCTTCCTGG
78060


 


CTAGGACGAT CCTTCATCTT GGAGCATGAG ACCTGGGTCT CCCTCATGGG GGAGGAAGGG
78120


 


GCTGGGGGGG GGCTCCAGGC TCAGCCTCAC CAACTTTCCT TCCAGACCAT CAGTGCTTAC
78180


 


TATGCAAGGG TTGCCGCCCC TGGGTCCACC GGCGCCACCT TCCTGGCGGT CTGCCGGGGC
78240


 


AAGGTGAGCT CTCCAGGGCC CTCTGCCCTG ACCTGGTTGC CTGTTCCCTG GTGGGTGCTT
78300


 


ATGGCTCCCC AGCAGACTCT GGGCCCTGGG GGCTGCCCGG TCCCCTCCTT GGGTCCCACG
78360


 


AGAGCGACTG CTGGCCCTGC TGGGAGCGTG TCCTGCTCTG GCCCTGGGCA GGCAGGATGG
78420


 


GAGTTTCCTG GCCACAAGAG TTGGAGGTGG CGTCTGGGAG CTGTGGACCC CAAGTGGGGT
78480


 


CCTGACCCAC AGATGGAGCT TCCTCCCACC CCTGGTTGGG GACGGAGCCT CGGGGAAGGT
78540


 


GGCTGGGCTG GGTGTGGGCA CCAGGGAGAG GAGCCCCCAC GGCCCCAGGC AGCTCCCTGG
78600


 


TGTGTCCCCT AGGCCAGCGA GGGGCTGGAC TTCTCAGACA CGAATGGCCG TGGTGTGATT
78660


 


GTCACGGGCC TCCCGTACCC CCCACGCATG GACCCCCGGG TTGTCCTCAA GATGCAGTTC
78720


 


CTGGATGAGA TGAAGGGCCA GGGTGGGGCT GGGGGCCAGG TGAGTTACAG CAGGGTGGGG
78780


 


CTGGGGTAAG GCGGTCTGGT GACTGAGCCC CCGCCCCGTG GCCAAGGGAG CCCCCGTGAC
78840


 


CGAGCCGCCT CGCCCCACAG TTCCTCTCTG GGCAGGAGTG GTACCGGCAG CAGGCGTCCA
78900


 


GGGCTGTGAA CCAGGCCATC GGGCGAGTGA TCCGGCACCG CCAGGACTAC GGACCTCTCT
78960


 


TCCTCTGTGA CCACAGGTGC GTGCAGTCCG GTGGCAGGCG CGGCGCCAGG GGACACGCCC
79020


 


ACACCCCACT GGGCCCCTGG ACTCTCCTTC CCCACATGAG GCCCCGTCTC CTCCAGAGCC
79080


 


TCTCCGGCTA CTCGGGGTCA GCGTGGGGCC CCTGCAGCAG ATGAGGGTCT TCACTTCGGT
79140


 


GAACTGAACC CTTGAAGCGG CTGTGGGCAG GGCAGCAGGG CTATGGCCAC CCCCCAGGTT
79200


 


CGCCTTTGCC GACGCAAGAG CCCAACTGCC CTCCTGGGTG CGTCCCCACG TCAGGGTGTA
79260


 


TGACAACTTT GGCCATGTCA TCCGAGACGT GGCCCAGTTC TTCCGTGTTG CCGAGCGAAC
79320


 


TGTGAGTTCC TGCCCAGGGA GGGGATGAGG GTGTTGTCCC CAGAGGAGCC AGAAATGGGT
79380


 


CCACCCACCC CCATGGTTCT GCAGATGCCA GCGCCGGCCC CCCGGGCTAC AGCACCCAGT
79440


 


GTGCGTGGAG AAGATGCTGT CAGCGAGGCC AAGTCGCCTG GCCCCTTCTT CTCCACCAGG
79500


 


AAAGCTAAGA GTCTGGACCT GCATGTCCCC AGCCTGAAGC AGAGGTCCTC AGGTGCGGAC
79560


 


GGGCAGCGCT GGGTGGGCGG TGTGGGGGTG GCGGAGCGGG CGGCGTGGGG CGGGCAGCAC
79620


 


CAGGCGCCCA GGGCGGAGGC GACTCACCTG GCTTTGTGCG CTTCCCCTCC CACCTCCAAA
79680


 


GGCTGCCTCT CCCTCCTAGG GCAGGGCCCC CACGGGCTCC AACCCTCCCC TACAGGCAGA
79740


 


GAACGCCCCA GGCAAGGATG CCCCCCGAGG CTGAGACTCC CCCCAATAGC AGGGAGGACA
79800


 


CCCACAGGCA GGACCCCAAG TGCTGGGACT CTCCCCCAAG AGGGGCTTTG CCACAGGCAG
79860


 


GGACCCCAGC TGGGGCCCCC CGTGGGCTTC ACTGCGCACT CGGGTGCCCC TGCAGGGTCA
79920


 


CCAGCTGCCG GGGACCCCGA GAGTAGCCTG TGTGTGGAGT ATGAGCAGGA GCCAGTTCCT
79980


 


GCCCGGCAGA GGCCCAGGGG GCTGCTGGCC GCCCTGGAGC ACAGCGAACA GCGGGCGGGG
80040


 


AGCCCTGGCG AGGAGCAGGT ACAGTTCCAG GGCCTTGGGA TGGACACAGA CCCTCTGTCT
80100


 


CCTGAGGCCA ACCCGACCCC GCCCATCTGG CCTCAGGCAC CTCCCCACAC ACCCCTGTAA
80160


 


ATCCCCTGCC TGGCAGGCAG GCGGGCAAGC GGGCGGGGGA TCCCAGCTGC CTGGCTGTCT
80220


 


GTGGGTCCTC CACCCCACCT CACCCACAGG CTGCTGGCTC CCAGGTGGTG CATGCCCTGG
80280


 


CCCTCCGCGG GTGCCCCCCA CATCACTTTG GTTCTCTGGC GGGTCAGCTT GGCTCAGTGC
80340


 


ACTCAAGGTC GGGTGCCCCT GCCACTGGCT GCGCTTGAGG CTGGCCTTTC TCCACCAATG
80400


 


TGCTGCGGGT GGAACCCAGG TTCCTTCTTC CTTGGGGCCT TTTGCCCCAG AAGCCCATAA
80460


 


TTCCTCAGGC CAACCCGAAA TTTTCTCCCT GCTTCCTGCT GGGAGCCATT CCCCTCTTCC
80520


 


TGCCCATCCC TGCCCTTCAG GCCCCTGGAG TGAGCTCCAG GTGCAGGCAC CAGGCACCTG
80580


 


TGTCCCCTTC CTGCCAGCCC CTCGCTGTGG TCGGACTGTC TTCCCTGGAC CTGCTCTTAC
80640


 


AAGTCACCAC CTGCGAGCCT CATGAGCCCC TGGTGTGACT TGGACAGGAC CAAGTTGTGG
80700


 


CACTGTCACC GGGGTGTGCT GTGCCCCCCT CCCCCGACCT CCATCTTGGC TCAGGGCTCC
80760


 


TTGGGACCAT CTTCCCTGTG CGTCCAGGTG CTTTGGGACC CCAGAGTGTG TGGTTGGGGT
80820


 


CTGTGTGTGG TTGTGAGCTG TGTCCTCCTC AGGCCCACAG CTGCTCCACC CTGTCCCTCC
80880


 


TGTCTGAGAA GAGGCCGGCA GAAGAACCGC GAGGAGGGAG GAAGAACATC CGGCTGGTCA
80940


 


GCCACCCGGT GCGTGAGCTG TCCCTGCACC TGTGCCGACC ACCATAGACA CGCATGGGAA
81000


 


CGCAGCCGTG GGTGCCCCCA GCCACGGCTG GTCCCGATGG GACCAGGGAA TCCACCCCCA
81060


 


GGAGCTGATG TCCAGGGCAG CTGTGATGCT GACGGCCAGG GGCTCAAGTG TGTGGTTTCT
81120


 


TCTGCAGGGG GCTCATGAGT CCCAGCTGGA ATCAGGCCCC ACCCTTGGGC AGGTTTGGCA
81180


 


TGGGGCCTGC AGCACTGGGC TTGGCCCTGG CATTTCCCTC AAGTGTGGAT GCACACCTGC
81240


 


CTCATGTGAG GGACACAGCC CATTCCTAGC CTTGGATCAA AGAACGGAGT TATAGCCGGA
81300


 


GCCAGGAAGC CCCCTGCCTG CTGGAAAACC CCAAGTGTGG CGGCCTTTGT CCATGTCCCT
81360


 


TGGCTTCTGG GAAGAACTGG GTGGTGCCCA GGCAGGGCTG GTGCCATCAG GAAGTGGGTG
81420


 


GCTGCTGAGG GGCCTGGGCT GGCGAGGGCC TGGGTGGGGA GTGCCTGGGC CGCCCCTGCC
81480


 


TTGGTTTCCA CGTTTCCGTG TTGGTCTGGG GTGTGTAGAG AGATGGGCAC TGCTCATCCG
81540


 


GAAGCCCCTC CTTGTGCGCT GCCATCCTGG GAGCCTCAGC CGCATCCGCT GTGGGGCAGG
81600


 


GGGCTTGAGG GAGGAGGAGA GAGACGGGCC ATGCAGGACC CCTGGCTTGA GGCAGAGCCA
81660


 


ATCTACCCTT TGCCCATTCA CTGCTCTCAG TTCCCTGCCA GCCTCTCACT GTGTGACCTC
81720


 


AGACGGGCCC AGCCCCACAG CTTTCTTCCC GCAGCCCCTC CCTATGTCCA TCCAGCCAGC
81780


 


CAGTTTCTCA GGCAGCAGCC CCACCTCGGC AGTCACTGTC CCAGGGAACG CTCAATGTTC
81840


 


CAAGGAAGGC TCTGCAGCCC CAGGGACCAG ATGATGAGGC TGGCCCTGAT GGAGCCTCGG
81900


 


GCCTGTGTCC TGCAGGAGGA GCCCGTGGCT GGTGCACAGA CGGACAGGGC CAAGCTCTTC
81960


 


ATGGTGGCCG TGAAGCAGGA GTTGAGCCAA GCCAACTTTG CCACCTTCAC CCAGGCCCTG
82020


 


CAGGACTACA AGGGTTCCGA TGACTTCGCC GCCCTGGCCG CCTGTCTCGG CCCCCTCTTT
82080


 


GCTGAGGACC CCAAGAAGCA CAACCTGCTC CAAGGTGCCC TGGCTTGCAG AGGCCACCCA
82140


 


CCCTGAGGGC AGTGCTGCCG CCGCGTGTGG GGTGGGGGCC ATCTGGGTCC AAGGTGGTCT
82200


 


CTGTTCTCTA GAGAAAAAGG GGCACATGGG GACAGACGCC CCTTCCTCTA CAGGCTTCTA
82260


 


CCAGTTTGTG CGGCCCCACC ATAAGCAGCA GTTTGAGGAG GTCTGTATCC AGCTGACAGG
82320


 


ACGAGGCTGT GGCTATCGGC CTGAGCACAG CATTCCCCGA AGGCAGCGGG CACAGCCGGT
82380


 


CCTGGACCCC ACTGGTAAAT GGGGCCCCAG GTGGGACCCT CAGACTCCTG CGTGGAAGGC
82440


 


AGTGTGGGCC AGAGTCCTGG GCTGCTTGGG GTGGGCATCC TCGGGCCCTG CTTGGCCCCG
82500


 


CCTCTCTGTT CCCCTATGGG AGTGATGGGG GCCTCCACCT CCACCACCAG CACCAGCAGC
82560


 


ACCACCTCCA CCTTCACCAC CACCACCTCC ACCACCACCA CCTCCACCAC CTCCACCTCC
82620


 


ACCACCTCCA CCACCTCCAC CACCTCCACC ACCACCACCA CCTCCACCAC CACCACCACC
82680


 


ACCACCTCCA CCACCACCAC CACCACCACC ACCTCCACCT CCACCACCTC CACCACCACC
82740


 


TCCACCTCCA CCACCACCAC CACCTCCACC TCCACCACCT CCACCTCCAC CTCCACCACC
82800


 


ACCACCTCCA CCACCACCAC CACCACCTCC ACCTCCACCA GCAGCAGCAT CACTTGTTGG
82860


 


GGAGACCCTG TGCAACTCCA TGCACAGCCC TGTCCCTGCC ATAGCCCCGA CCCCTAAGCA
82920


 


CAGCCCTGTC CAACTGCCAC ACGTCCCCTG CCTCCCATGC ATGGTCCTGG GGGGTCAACT
82980


 


GCACACGCCA GGGTCCTAGG GTCCTAGACC CCTGTCCTCC CTGTTTCTGC CTCTGTTTGG
83040


 


GGTGGAGTCC AAGTCTCCAG AGGCGGAAGC ATCTGTGTTC GTGTGTTAAT GAACAGCCCC
83100


 


TACAGAGTTC CCCTAGTTCA CCCAGGGGGG AACCTAGCCT GTTGGGACGA CCCCAGATCC
83160


 


CTTCTGGGCT TGGTACTCAC TGGGATATCC TCATGCCTGC ACCCAGCCTA CGGCTCTGAG
83220


 


CTCCTGAGTG GGGCTTTGGC CTGCCCGCCA CTGTTCCAGC CCCCATCCAG CAGGCTGGTG
83280


 


TCTCCTCTGA TGCCCCCAGC ACCCAGGCGT GTACCTGCCT GGGTTTTCCC GCCCTGGTCT
83340


 


GAGGTGGGTG AGGCCTGGCC TCCCTAGCCA GCCCTGCCCC CCCACCCCAG GGAACTTTCC
83400


 


AGATGCTCCC GACCAGCTTT GTGGCTCTAC ATCTCTTCAT CAGGAAGAAC GGCGCCGGAT
83460


 


CCCAAGCTGA CCGTGTCCAC GGCTGCAGCC CAGCAGCTGG ACCCCCAAGA GCACCTGAAC
83520


 


CAGGGCAGGC CCCACCTGTC GCCCAGGCCA CCCCCAACAG GTAGCTGACT CCTGAACCGT
83580


 


GTGCAGCCTA CGACTTGGTG GGTCCCTCAG TGGCTTCACG AGGCTAACTC TTGAGTGTGG
83640


 


CCGGGGCTGC CCCTGTGGGG AGCCATCTCA TGGTGGGGAC TGCTCCCGGT TCTGCACCCC
83700


 


GCAGTTGTCC TGAGCAGCTC TCCAGGAGTT CCTGGAGGAA GGGCGGGCAG GGCGGTGGGA
83760


 


CTCTCAGTCC TCCACCCCAG CGCCACTCTG AGCCATGCTA CTCCCACACC AGGAGACCCT
83820


 


GGCAGCCAAC CACAGTGGGG GTCTGGAGTG CCCAGAGCAG GGAAGCAGGG CCAGCACGCC
83880


 


GTGAGCGCCT ACCTGGCTGA TGCCCGCAGG GCCCTGGGGT CCGCGGGCTG TAGCCAACTC
83940


 


TTGGCAGCGC TGACAGCCTA TAAGCAAGAC GACGACCTCG ACAAGGTGCT GGCTGTGTTG
84000


 


GCCGCCCTGA CCACTGCAAA GCCAGAGGAC TTCCCCCTGC TGCACAGCAA GTGGCCCTGG
84060


 


CGTGGGGAAC AGCCGGTGGG GTGGGGGCCA GGGGACAAAA TGGGGGCTGT GCCGGGTCTG
84120


 


ATTGAAGCTC CCCGCAGGGT TCAGCATGTT TGTGCGTCCA CACCACAAGC AGCGCTTCTC
84180


 


ACAGACGTGC ACAGACCTGA CCGGCCGGCC CTACCCGGGC ATGGAGCCAC CGGGACCCCA
84240


 


GGAGGAGAGG CTTGCCGTGC CTCCTGTGCT TACCCACAGG GCTCCCCAAC CAGGTAGGGC
84300


 


ACCTGCCTGG CTGCTCCTGG CAGCGCCCCA ACCGCACGCA GCCCTGGGAG TGAGCAGCAA
84360


 


AGCCCCAGGC CCCCCTCAGA CTCAAGTCTC TGTCTCCAGG CCCCTCACGG TCCGAGAAGA
84420


 


CCGGGAAGAC CCAGAGCAAG ATCTCGTCCT TCCTTAGACA GAGGCCAGCA GGGACTGTGG
84480


 


GGGCGGGCGG TGAGGATGCA GGTCCCAGCC AGTCCTCAGG ACCTCCCCAC GGGCCTGCAG
84540


 


CATCTGAGTG GGGTGAGCCT CATGGGAGAG ACATCGCTGG GCAGCAGGCC ACGGGAGCTC
84600


 


CGGGCGGGCC CCTCTCAGCA GGCTGTGTGT GCCAGGGCTG TGGGGCAGAG GACGTGGTGC
84660


 


CCTTCCAGTG CCCTGCCTGT GACTTCCAGC GCTGCCAAGC CTGCTGGCAA CGGCACCTTC
84720


 


AGGTTGGTGC CTGGCCACTA CAGTTCCTGC TGGGTGTAGC CCCAGGTGAT GGGCTGAGGG
84780


 


GGAAAGGGCA GGCCCTTGTC CTGGTGGCAA CGCCTGGCAG ACGTGTGCAG TGGGCCGGTT
84840


 


GTCTCACAGG CCTCTAGGAT GTGCCCAGCC TGCCACACCG CCTCCAGGAA GCAGAGCGTC
84900


 


ATGCAGGTCT TCTGGCCAGA GCCCCAGTGA GTGCCCACGG AGGCCCCCAG CACACCCAAC
84960


 


GTGGCTTGAT CACCTGCCTG TCCAGCTCTG GTGGGCCAAG AACCCACCCA ACAGAATAGG
85020


 


CCAGCCCATG CCAGCCGGCT TGGCCCGCTG CAGGCCTCAG GCAGGCCGGG CCCATGGTTG
85080


 


GTCCCTGCGG TCGGACCGGA TCTGGGCCTG CCTCTGAGAA GCCCTGAGCT ACCTTGGGGT
85140


 


CTGGGGTGGG TTTCTGGGAA AGTGCTTCCC CAGAACTTCC CTGGCTCCTG GCCTGTGAGT
85200


 


GGTGCCACAG GGGCACCCCA GCTGAGCCCC TCACCGGGAA GGAGGAGACC CCCGTGGGCA
85260


 


CGTGTCCACT TTTAATCAGG GGACAGGGCT CTCTAATAAA GCTGCTGGCA GTGCCCAGGA
85320


 


CGGTGTCTTC GTGGCCTGGG CTTGGTGGTG GGAGTTGAGG GACAGGGAGT TGGCAGAGGC
85380


 


CCCTCCCAGC CTGCCATGTG ACACTGTACT TCCTCCACGG TGGGCTCAGC CCTGCCCTCA
85440


 


TCCTCACAGC CGCAGCCAAG CTGCAGTTGG TAGGGGATCC ACCGACACAC CAGGCTGCCT
85500


 


GGGCTGGTCT CTGGGTTGGG AGCTGCCCCA GGTGCTGAGG AGGGCAGCTC CCTGGCTGGT
85560


 


GAGGCCCCTC CCAGAACCAC CCTTGGACTG AGCTCTGGGG AGGGATGGTA CCAGGTGGGT
85620


 


GAGGGGGGCT GCCTGGGGAG GGAGGGGTTC CTATGGGGCG TGGCGAGGCT GGCCCAGCCC
85680


 


TCTCCCCGCC CATATATGTA GGGCAGCAGC AGGATGGGCT TCTGGACTTG GGCGGCCCCT
85740


 


CCGCAGGCGG ACCGGGGGCA AAGGAGGTGG CATGTCGGTC AGGCACAGCA GGCTCCTGTG
85800


 


TCCGCGCTGA GCCGCGCTCT CCCTGCTCCA GCAAGGACCA TGAGGGCGCT GGAGGGGCCA
85860


 


GGCCTGTCGC TGCTGTGCCT GGTGTTGGCG CTGCCTGCCC TGCTGCCGGT GCCGGCTGTA
85920


 


CGCGGAGTGG CAGAAACACC CACCTACCCC TGGCGGGACG CAGAGACAGG GGAGCGGCTG
85980


 


GTGTGTGCCC AGTGCCCCCC AGGCACCTTT GTGCAGCGGC CGTGCCGCCG AGACAGCCCC
86040


 


ACGACGTGTG GCCCGTGTCC ACCGCGCCAC TACACGCAGT TCTGGAACTA CCTGGAGCGC
86100


 


TGCCGCTACT GCAACGTCCT CTGCGGGGAG CGTGAGGAGG AGGCACGGGC TTGCCACGCC
86160


 


ACCCACAACC GCGCCTGCCG CTGCCGCACC GGCTTCTTCG CGCACGCTGG TTTCTGCTTG
86220


 


GAGCACGCAT CGTGTCCACC TGGTGCCGGC GTGATTGCCC CGGGTGAGAG CTGGGCGAGG
86280


 


GGAGGGGCCC CCAGGAGTGG TGGCCGGAGG TGTGGCAGGG GTCAGGTTGC TGGTCCCAGC
86340


 


CTTGCACCCT GAGCTAGGAC ACCAGTTCCC CTGACCCTGT TCTTCCCTCC TGGCTGCAGG
86400


 


CACCCCCAGC CAGAACACGC AGTGCCAGCC GTGCCCCCCA GGCACCTTCT CAGCCAGCAG
86460


 


TTCCAGCTCA GAGCAGTGCC AGCCCCACCG CAACTGCACG GCCCTGGGCC TGGCCCTCAA
86520


 


TGTGCCAGGC TCTTCCTCCC ATGACACGCT GTGCACCAGC TGCACTGGCT TCCCCCTCAG
86580


 


CACCAGGGTA CCAGGTGAGC CAGACGCCTG AGGGGGCACC ACACTGCAGG CCAGGCCCAC
86640


 


TTGTGCCCTC ACTCCTGCCC CTGCACGTGC ATCTAGCCTG AGGCATGCCA GCTGGCTCTG
86700


 


GGAAGGGGCC ACAGTGGATT TGAGGGGTCA GGGGTCCCTC CACTAGATCC CCACCAAGTC
86760


 


TGCCCTCTCA GGGGTGGCTG AGAATTTGGA TCTGAGCCAG GGCACAGCCT CCCCTGGGGA
86820


 


GCTCTGGGAA AGTGGGCAGC AATCTCCTAA CTGCCCGACG GGAAGGTGGC TGGCTCCTCT
86880


 


GACACGGACA AACCGAGGCC TGATGGTAAC TCTCCTAACT GCCTGAGAGG AAGGTGGCTG
86940


 


CCTCCTCTGA CATGGGGAAA CCGAGGCCCA ATGTTAACCA CTGTTGAGAA GTCACAGGGG
87000


 


GAAGTGACCC CCTTAACATC AAGTCAGGTC CGGTCCATCT GCAGGTCCCA ACTCGCCCCT
87060


 


TCCGATGGCC CAGGAGCCCC AAGCCCTTGC CTGGGCCCCC TTGCCTCTTG CAGCCAAGGT
87120


 


CCGAGTGGCC ACTCCTGCCC CCTAGGCCTT TGCTCCAGCT CTCTGACCGA AGGCTCCTGC
87180


 


CCCTTCTCCA GTCCCCATCG TTGCACTGCC CTCTCCAGCA CGGCTCACTG CACAGGGATT
87240


 


TCTCTCTCCT GCAAACCCCC CGAGTGGGGC CCAGAAAGCA GGGTACCTGG CAGCCCCCGC
87300


 


CAGTGTGTGT GGGTGAAATG ATCGGACCGC TGCCTCCCCA CCCCACTGCA GGAGCTGAGG
87360


 


AGTGTGAGCG TGCCGTCATC GACTTTGTGG CTTTCCAGGA CATCTCCATC AAGAGGCTGC
87420


 


AGCGGCTGCT GCAGGCCCTC GAGGCCCCGG AGGGCTGGGG TCCGACACCA AGGGCGGGCC
87480


 


GCGCGGCCTT GCAGCTGAAG CTGCGTCGGC GGCTCACGGA GCTCCTGGGG GCGCAGGACG
87540


 


GGGCGCTGCT GGTGCGGCTG CTGCAGGCGC TGCGCGTGGC CAGGATGCCC GGGCTGGAGC
87600


 


GGAGCGTCCG TGAGCGCTTC CTCCCTGTGC ACTGATCCTG GCCCCCTCTT ATTTATTCTA
87660


 


CATCCTTGGC ACCCCACTTG CACTGAAAGA GGCTTTTTTT TAAATAGAAG AAATGAGGTT
87720


 


TCTTAAAGCT TATTTTTATA AAGCTTTTTC ATAAAACTGG TTGTAGTTGC ACAGCTACTG
87780


 


GGAGGGCAGC CGGGGACACC TGAGCCGCCC GCTGTGCCCA GATCCCTCAG GCTGCCTGCC
87840


 


ATCAGAACTG CTGCCCGGGG CTTCCCCTAC CTCAGACAGA CCCTCCCTGG GAGGATCAGT
87900


 


GGGGAGTGCC ACCTCTGCCC CCAGTGGCTG TGGCACGTGG CAGGGGCCCC TGAAGCTCAG
87960


 


CGAGGGTCAG GGCCTGGGAG GGTATCATTG CTGGAAGAAC AGGATGGGGC TCAGGCCAGC
88020


 


CCTAGTCGCC GGGGCCCACA CTAACCCCCC ACTTATGAAT TCCTCCCACT CCCAACTCAC
88080


 


AGGGGATTTC CCGAGAGGGG ACCTGCCAAA GACCTCCTCC AGGCCTCCCA TGCTTCCCGG
88140


 


GAAGTGAAGC TTCTCCCCCT CTGGGGCAGG CTCTGAAGCC TCCCGATGCA CCCAGAGCAA
88200


 


CCAGGGCGCT GCACCAGCCA CTCGCCTCCC CAGCACGGCC AGCTTCCCGG GGCTGGAGGT
88260


 


CCCCCCCAGG TCCTGGGAAC CAACCTGCAG AACACACACA GGGTCCCCTG GAGAGGACGC
88320


 


GGGGACTTCC AGGGCCCGAC TCCTGTGAGT CACAGCCCCG CAGCTGCTGC GCCACCCCCA
88380


 


CCCTGACTCA TGCCCCTTCC CAGCAGCTCC TCCCAGGACC CCATGTCCTT CCCACATCCG
88440


 


CAGGAAGGGA GTGCCTGGAC TCTCCAGGCC CACCTGGGGA GCCCCTCACC TGCCCACCAG
88500


 


CCCCTGAGCA GCCCAGTAAC ACCATCACCG TGTCCAACAG CCAGGAGCCT CCACCCTCCA
88560


 


GGAGGGAAGG GATGGACAGA GCCACACTCG CCGTCTTTAT TTTGCACTCA CCCTGGGTGA
88620


 


CACTGGGCAG GCCGCTCCTG CCCACAGCCA GACTGAGGAA GAACACACCA CTCGGCAGGC
88680


 


CCAGTGGGGT CCGTGCAGGG AGGACCCCAG GACCAGCCTT ACTCCCGAGC AGGGGACACA
88740


 


GGGCCCCACA GAGAACCCCT CCGGGAGGTT CTCTCCTGGC TGGGGGAGGG CTCTGGACCC
88800


 


CCACAAACAC TCCCCAACTT GCGGGGCTGG GGCATAAAAA CAGCCACTCC CAGCAGGCCC
88860


 


CCTCAGCTTT TTGCATCAGT CAGCTCCCTC CCGGGGGATT AGGGTGAGGT GAAGCCAGGC
88920


 


CCAGGCGTGG GGTATAGGTC TTCCCCCGCA GGCCTCAGCC CTGTCCCGAG GCTGCATCAC
88980


 


AATCCAGGGC CCCCGCTGGC CTTTGGGAAC ATGGCCTGGG TCTTCCTCAA GGCAAGATCA
89040


 


GCCCCAGACC ACTTCCGGGG TCACGGGGTC ACAGGGCAGA AGCCAGATGG CAGCCATGGC
89100


 


TGACGGGCCT CCTCCTCGAT GGGGCGGAGA CAGCCACGGG GTCTCCCGAG GGTCCCACAG
89160


 


GGCTGTCCTC ATGCAGCCCA AGCCAGCCTG AGCACTGGAG CCCCAATTCC CAACCAGGTC
89220


 


TCCCTCAGAC CCCCCAGAAA GGGCCTCGAA AGCCCGCCGC TGCGCCCTGT GGAAAGGCTG
89280


 


CCGCTGCAGG GCCTGGGCCA GCCGGGCTGC CAGACTCCCC TCCAAAGCCT CCGCATGCCT
89340


 


ACGCTTTTCC AGACATAGAG GAAAGTTTGT CTTCGAGAAA ACAAAGTAAA TAGAAGAACC
89400


 


CCAAAGCAAA GCAAACCCAC CCCCCAGATC AGCAGCATGG GAGCCAACAG GAGGCCACTC
89460


 


CTCCAGCACC AGGGGACCAG CCGTCCCGAC GGCAGCGCGG CTGCGCCTAC GTGATGTCCC
89520


 


TCTGCCGCGG CGGCCGGTGC ACATTCCGCA CGACACACTT CACCATCCAC TCGATGCCCT
89580


 


CGCGCACCCC TTTGCTGTGA AGACAGCGGG TGTGAGGCGG GGGGTCTCGG TCCCCAAAGC
89640


 


CCCCGCAGGT GCAGCCCCCA CTCACCCTGT GAGGGCCGAG CAGGCCTGGG TCAGGCAATC
89700


 


GCGCCTGCCG ATCTTGCTGG TGCAGTCGCT GAAGGCCGTC TTGATGTCAG GGATTGAGAG
89760


 


GCACGTCTGG GGGAGGTAAG GCCGTGAGGA GCAGCCCCCA CCTCTGGCCC TGTCCTGCCT
89820


 


GTGGGCCCGG GACTCTCAGA AGGGCGTATG CCCTTCACCC CAGGGAAACA GCCAGAGCTC
89880


 


CACCAGGGTC CCAGTGTCTC CCACAGAGAC CACAGCAGTG AGGACCCTGT GCTCAGCCCG
89940


 


AGGCTGAACA TGGCTGGTAG TGCCTGAGAC AAACTAGACG TCCACACGGC TCCAAGGAGT
90000


 


CCACCCCCCA TCCCCTCCCT GGGGGACACC CTGAGCCCCG AGGTGGGGCG CTGAGGACTG
90060


 


AGGCCTCCTG GGCAGTGGCG GAGGCAGGTC CCAGGGGCCC ACACAGCCGG GGATGATGGA
90120


 


GAGGTGGGAG CCCTGCATCA GTGATGGGGG CAGTCTGCAG TCATGGTGGC TTCTGCTCAC
90180


 


AACCACCTGC CCAGTCTTCA AAAAGCAGCC CTCCCCTCCC CTTTTCCTCC GAGGGGAGAC
90240


 


CCCTGCCCCG TACCAGATGT CCCTCTTGTC GGCTGAGATT GTAGGGGAGG CCAGCCTTAC
90300


 


AGGCTGGGGG CAACAGAGCC ACCCCAGAGA AGGCAGGAAG TGAAGATTCA CCCGGCCCTC
90360


 


TGGACGCCCG GCTGCTTCTG TGCAAACCCA CTCCAAGAGA ACAGCTAGAA CTCAGCGTGG
90420


 


CCAGTGCTCC CGGGGGCAGT GGCACCTCAG AGGGGTCTTG AGGGGCTGCC CTGGGGGTGG
90480


 


GGCTGGCACA GATGCCACCT CCAAGGGTAG CAGGAACAGG TAAGGGTCAG AGCTGACTCC
90540


 


CACCAGGGCC CCAGCATCAC TTCTTTGAGC TCTGAGTTTC ACCTGGGTGT CCCCACAGCT
90600


 


TGGCCACACA CTCCTGAGAC ACGGCCGCCC TCCTGGGGAG AGGTGCCCTG CATACCAGGA
90660


 


AGAGGCCTCT GGGCGCCTGC CCTGAGGTGG GAGAACCTCC AGGGCTGGCA GCAGCAGGTC
90720


 


TGGAGAGGAA CCAAGCTTGG GAAGCTGCTG GGGGCAGGGC AGGCCTTGAG AATGGCTCTG
90780


 


TACCCCCTGG GCAGTCACTG GGCCTGGGGT GTCTGGGTGC ACACCTACTC CCCTTGCTGT
90840


 


GGGGGAGGCT GGGGACTCGG GAAGCTGCTG CGGGAGGCAG GGGTGGGGCT CACCTCCACA
90900


 


TCCTGCTTGT TGGCCAGCAC CAAGACGGGG ACACCGCACA GCGCCTCGCT GGTCACCACC
90960


 


TTCTCTGGGG AGGGCAGGAG AGGCAGCGCC TCACACCCAG CATCCTGCCT CTGACTGCCC
91020


 


AGGGGCCCAC AGGCGTGGAC ACTGTGACAG CCACTCCCTC TGCCCCCCCC CCGTCACCCA
91080


 


CTAGGCAGGA GCACTTCTGA CCAGACACTG AGCCTGCCCC AGGCACAGAG CTGCCCAAGC
91140


 


TGGACCTGCC CCCACTCACC ATCCATCCCT CCCAGAGCAG CCAGGCCGCA CTCACCAAAC
91200


 


GCCTGCTTGG ACTCAGCCAG CCTCTCCTCG TCGGTGGAGT CAATGACGTA GATGACGCCG
91260


 


TGACACTCCG CATAATACTG GGAGGAAGCA CCAGGAGTTG GGGCTCAGTC CCCACCCTGC
91320


 


CAAGGGCCAG CAGAGCCAGG CCTGTGTCAT GGCCACAGTG AGGGGCTCAC ATGAGGAAGG
91380


 


GGCAAGAGGG CAGCCCCCAA CTGCAAGACC CTTCTGGGAT GCATTCTGGG GTTGCGGGGA
91440


 


GATCTGGTGG AGGTGTCCCC AGACGCTGCT CCTGAGAACC TGCCGGCAAC CTTTGGCCTG
91500


 


ATGGTGGCCA AAGGTGAAAG ACAGGGATTG GGCCAGGCGT GGTGGCTCAC ACTTATTATC
91560


 


CCAACACTTT GGGAGGCAGA AGCAGGAGGA TCACCTGAGC CCACTTCACG GCCAACCTGG
91620


 


GCAACACAGT GAGACTCCGT CTGTACAAAA GCTTATGGTA ATGTGCGCCT GCAGTCCTAG
91680


 


CTACTCGGGA GGCTGAGGTG GGAGGATGGC TTGAGCCTGG GAGGTTGAGG CTGTAGTGAG
91740


 


CTCTGATCAC ACCACTGCAC TCCAGCCTGG GTGAGAATGA GAGACCCTGT CTCAAAAAAA
91800


 


AGATAGGGTT TGGGGGCTGG AGGAACCTAG ACCACAGCCT GGCCCGTTGA GGGAGTGCAC
91860


 


CTGTGGGGCT CTGTGCCAGC ACCTCGCACA GGGAGGGAGT GTGGCCATGC GGATAAGACT
91920


 


GACCAGCACC ATCTACGAAG CGAGCCTTCC CTGCCAGGAC AGGGCCAGAG TCACTGAGCT
91980


 


CAGACCTCTG CAGCCTGGGC TGGTCAGTCC TGGGCTCGCT GGCAACACTC CTGGGCAAGA
92040


 


CAGGGCACAG CCCCTGCAGC CTCAGGTACA AGTGCTGAGC CCTGGACCAG ATGAGTGCAC
92100


 


CTCTATCTCA ATCAGAAAAA AACACAGCAA ACTCCGCGTC CACGTGGAGC AGACAACAGC
92160


 


TCACATTTGC CACTTTGCCT CCAGGCTGTG CCAGCTCTCC TGTCCAGGCA TGAGTGCCCA
92220


 


GAGACCTAGA ACTGGATGCT GACCAGGTAG GACAAGCTGG TGGTCAGTGT GTTAAGACAC
92280


 


ACACACCCGA GAGCATGAGA AGCCAGGAGG CACAGCCCAA CTCTCCGAAA TCCTTAGGGT
92340


 


GTCTGAGCAG GGAGTACCAG ACAACCCCAT CCCAGTGCCA GACAAGCTTG TGCACCTGCA
92400


 


CTTCCCACAG AGGAGAGAAG CCTGTGCACC TGCACTTCCC ACAGTGGAAA GGAGGAGGCC
92460


 


CAAGGCCAGG CCCCCCCACC CCCAGGAACT TCCCACAGTG GAGAGGAGGC CCAAGGCCAG
92520


 


GCGCCCTCCA GGGTTCTGCA GGTAGCGAGG CCCCCCCACC CCCAGGAACT TCTCTGGCCT
92580


 


ACAGACAGGT CCCACACAGA GGCCGCCAAC CCCTCAAGGG ACCCTGCAGT GTGCCGGCTG
92640


 


TCTGCTGCTG ACACAAGGGA GCAGGCGGAC CCTAAGGTGG AGACCTCTGT GGCAGGAGGG
92700


 


GCGGCTCTGT GGAGGCTGCA GCAAGCCCAG TGAGAGAATC TCCACGTGGC TCCTGGGGCT
92760


 


TCTGAGCAGG GTGGCAGAAG GTTCATGTGC AACCGGGTCC TGGACCATGG GACCACGTGG
92820


 


CCAGAGCCAC CCATCACACC TACCAGGCAC AAGGTGCACA GCCCAGCAGG GCCGCAGTGG
92880


 


ACGGGAGCGA CACCTCAGGG CTGAGTGCGG GCAGGACCCA GAGCCCCACG CCCCAGTGGA
92940


 


GGCGTCACAG CAGTGGTCAT TGTGGGGTGC CCCACAAGGA GGGGGAAGAG GGAGGTGTCC
93000


 


CAGCGTGGCT CCTGGCTGGC CAGCTGACCC CAGTGGAGCA GTCAGAGGGA CTGTGGGTCT
93060


 


GAGTTTTTCT CCCCAGCAGC AATGGGAGCT CCCCAACTGC AAAGTGCCAG CCAGCCTGAG
93120


 


AGACTAGTGT TACAGCAAAG AACCCAGGAG CTGAGGTCCT GGCACATGCC ACACATGTGG
93180


 


ACACCAACCC AGGGTCCAGC CCCAGGACGA GGCCAATTCG CAATGACGCC CCTTTCTGTG
93240


 


GTGCTGGCTC TGCACAAGGA TGCAGGATAC AGGAACCAGG GTGGGAGCAG GGGCCTCCCT
93300


 


TCCGGTCCCT CCCAGTGACC TAGGGGGGTC CCTGCAGCTG ATCCTCCCAG CTCTGAGCTC
93360


 


AGCAGGGTCA GGGGTCCCGG CCACTAGAGC AGCACATACT CAGCAGACAC GCTGAATGAC
93420


 


GAGCCACAGC TGCCTCATGG GCATGACTTG CACCTCATGT CTAGGAGACC CTGGTGGGCA
93480


 


GGAGATGGGG CTGCCATCCC ACAGCTGTCC CACAGCTGGG GACCCAGGGA GCCACTGGCC
93540


 


CCACCACGGT GGTGTCTGGA GAAGGGCTCA GACTGCCAGG AAGTCGCACC CCAGCAGAAG
93600


 


TGGTAGTGAA TTGGGAGGGC ACTCAAGGAA GGGCTGTGCA GCCCCAAGAC CAGCAGCAAG
93660


 


GATGGGCTAC AGTGGCCCCC TTAAGTCTCC CTCTTCCAGT TTCGCCTTAA GAGAGGCCCT
93720


 


CAGGACCTTG GAGGAACCCC TCTCCAACGT GGAAGTGTGG GTCCACATAG GGCTGCAGCT
93780


 


GTGGCCAGTG CAGGCATCTC TGGCCCCACT GTATTCTTGC TTCATGTTGG AGAACACTGC
93840


 


ACCACCAGAT GGTCTCATTT TGGTTTCTGT GGGACCCACT TTGGCTGCAA AGAGCCACAC
93900


 


TGCCAGGTCA CACCTGCCCA GGGCAGCCCA CACTGGGGAC CCACCAGGCC ATGGTGTGAA
93960


 


GTCCCGGCCA GCCTGGCCCC ACATGGCACA GCATAGCCAG TTCTCCTCCA GGGCTCCCTG
94020


 


CTGGGCCAAC CACAGCTCTG CGGATCCTGC TGCCTGAGTC GACCTCTCCT CTCCCGTCCT
94080


 


CCCTGCCTTC CTGGTGCCGA CCCCCAGTGT GCATCCTGTA CCTCGACCTG TCTCAGCATC
94140


 


TGTGCCTGAG ACACCGGCCT GTGACAAGAT CATCATCATC TGTGTCACTC CCCAAGCATG
94200


 


CTGCGCACTG GACACACAGG CCCTGACTCA ACTTGTCCTG TCTGACTTCA GTGGTCCTAC
94260


 


AGGATCTATC AGAGATCACT TGGCCATGGG AGAAATGTCT TCTTGGCTAG AAGTCACAGC
94320


 


AGGAGGGGAC ACTTTGGGGG CGCCTAGGAA AGGGGAACTA GGATCAAAAA AGAGATCAGG
94380


 


ACCTGGGCAC TCAGCTCTAG AGATGGCATC AGGGCAGCCA AGGCACTGGG GACACCCCAC
94440


 


ACCCACTGTG CCAGCCTAGG GCAGGGAGCC CGAGGAAGCC ACAGGCTCTG CCCTGCTCAG
94500


 


TGCTGGACTC AGTGCCTGGC CCAGGCTGAG AAGGAGATAA ACTGCAGCCT TGGGGGTGTG
94560


 


GGGAAGGGGC ACCACACTGG GATCTCAGAA ATGCCCAAAA CCTGTGTCAA AATAGGAGAC
94620


 


TGCCCCTGTG ACACCCTGAG GAGTCTTCTG GTGATCATGG AAGAACAAAT GTTAAGCTAG
94680


 


AACTGAAGGA ACCTCATCAG GGGAGAGGCA GCCATCCTGC CGTCCCCACA TCTGGTCTTT
94740


 


GCCATTTCTG TGTCCTGTGG TGGTCAGCAG CAAGGTCTCT GAGCCGAAAG GAGGCACTCA
94800


 


CTTTGGAGGA GTGCAGGGTC CCCAGGTCCC CACACTTTGT CTTGTCCTGA CTGAGAAAGA
94860


 


AACAGACTGC CCTGACCTCT CTGACTTGGC CAGCGAGGTT GCCCTTAGGC TCAAACCCAA
94920


 


GCCAGGGTTT GAACATTCCC AGACACTTGT AAGATGTTTA GGTTGTTAAC ATAATGTTCA
94980


 


GGTTTCAAAA CATTGAAAGA AACTAGCCCC AGCCCTGAAC CCAGATCCCC CCCGGCTTCA
95040


 


GGCATGACCA GTGAACACGC CCTTCTCTCA CTGGTCACCT GAGGATGCCG CACTCTGTCA
95100


 


ACAGGTTCCC CTAATACATG CTCTGATCTG ATCGCCTTGG CATTTAGTGA TTCTTTCCCT
95160


 


GGAATTCTCC ACTGGCCCCA TCGCAGGGAA CTCCCAAGTG GGAAACTCCC CTACCACCAC
95220


 


TTTTGGGGCA ACTTCAGCTA AGGGTTCAGC TGGGACAAAA CAGGGAGCCA CTCGGGAACC
95280


 


TGGGACAGGA CCAGAGAGAA AACCCGAGGG ACAGAGTGGG TAAGGAAAGC TGCTGAGGAA
95340


 


GGGCCCAAAG GGCACTCTGG AAAGAAGTGG CACTGGAGGG CTGGGGTGGG GGTGGTCCTG
95400


 


GCCAGGGAGT CTTACCTTGT CCCACAAAGA CTGCAGCTCT TCCTGCCCTC CTAACTCCCA
95460


 


GAACATGAGC CGAGCCTTTC CCACATCCAC AGTGCCGACT GGGGAGAGGA GGAAACAGGC
95520


 


AACGCTCATG ACCTTGGTCC TCGACACACC CAGTCCCAGC TCTCCCAGGG GATGGGGCAA
95580


 


ACCATGCTGG TGCCACTCAA ATGAGACTTG AGAGGGGCCC GACAGGGCTG TGGCCACGGG
95640


 


CCAGCTGGAC TGTGAATATC ACGGCATCCT CAAGGCCCCA AACCCACAGC CTGCTATTGA
95700


 


GACCCTTACT GTTTAGGCCC ACGGTGGTGG TGATTTTGGA TAGACTCATC CCCTTGTAGT
95760


 


TCTTGTTAAA TCGGGTTTTC GACTGCTCCA GGAAGGTCTG AGGAGAGAGG CAGAGGCGAA
95820


 


ACACATCAAG GAGGGGCTAT ACTGGCTTCC AAATATCCTT ACTCAGGTCT GTTCTTTAAA
95880


 


AGACAGAAAC AGAAACAGAG CAACACTCTG CTCTTCAGGA GGCTGGTGGT GACTATCCTG
95940


 


CCGTCTCAGG TGAAATTTGG CTTCCGTCTG GGTAGTGAAC GTGCAGCTGA CAGCACAAAA
96000


 


CCGAAGGGGG CGCCGCCAGG CCGTGGGAAA GGTGCGCGCA AGGGCGTGGG CACTCACCGT
96060


 


CTTCCCAGCA TTGTCCAGGC CCAGGATCAG GATGCAGTAC TCGTCCTTCT GAAACATGTA
96120


 


CTTGTACAAG CCCGACAGCA GCGTGTACAT CCTGCCCTGG GCACCCCAAC ATAGGTCAGT
96180


 


GTGCAGCCAG AAAGCACCTC CCCTCCCCCG GGCTTCTCCA CGGTGGTCAG TGGCGCCCCA
96240


 


CGTCCAGCCG ACCGCTCAGG ACGAGAGCCT GGGGGCCATT CCCGACTCCT CGTCCCTCTC
96300


 


CCACCCCGTC CCTCTGTAAC TTCTCCCAGG TCAGCCGCCA CTGTGTCCTG CTCACAGCAA
96360


 


TGACTGCGAC CTCTCCGCAT ACACATCGGT TCCGGCCCCT CCCCTGCTCG CGGGACTACC
96420


 


CAGCCGGGTG TTCACAGTGA GCTCACCCGC GCTCCCGCCC TCCCCCGAGG CTTCGCTCCC
96480


 


ACGCTTCACG CGCGCGGAAC GGGGAACACA CTCGCTGCAG CCCCGCCTGG GCCACGGCAC
96540


 


CCTCGAGCGC CAGCCCCGCG CCCCACCCGG GAGCAGCGAG CCACCGGCGC GCTCCCCAGG
96600


 


AGCCCCTGCA GGCGCCGGGT AGGGACGCCC CATCACCCCA TTTCTTAAAA CGGGGACGGC
96660


 


CCTGGGGGGA GCGGACTACA GGGCGGGTGA GCAGCGGCGC GGCTGCTCCT GGAGTGCACC
96720


 


TGGAGGCGGC GCGCGGCTGG CAGGGAACGA CTGCGAAGGA AGAACCTGGG TCGCGGCCCC
96780


 


CGGCTACGTC CGCCCCAAGC CGCCGCCGCC AGGTCTGAGG CTCCCCGACA AGCAGCCAAA
96840


 


GCTGGCTCCT GTCACACCCG CGTCCCACCT CGAGTCCTGG GCCGCCCCTC GGGCCTCGCG
96900


 


CCTCACCGCA CAGCCTGCGG CCTACCTGCG TCCGCCGCGC CCTCGGAGCC GCTGCTGCTG
96960


 


ACCCCCGCTG ACCTCCGCTG ACCCCGCGCT AACCCCGCGC GGCGCCTGAC GGGACGCGGG
97020


 


CCGGCCTCAG GGAATGAGCT GAACCGCGTC CCAGCGGCCT CCGCGCTCCG CTTCCCGGCT
97080


 


GCCCCCGCGC GCCAAGCACT TCCGGAAGCG GCGGCGCTCG GGAGGAAGTG CCGATCGGCT
97140


 


GCTGGGGCGA AAAGGGGGCG CCGGGCCGCT CTAGCCGGTG AGGCCGGCGG GCTCTCTGTG
97200


 


GCTGCGGCTG GGAAACCGCG CGGAGGAGGT GCCCGCCCGG GGACCACGTG GCCGCGGTTT
97260


 


GCGGGGACGC GGCCCTGGCC AGACAGAAGA GACGCCGGGC GGGGGGGCGC GGCCGGCCTG
97320


 


GAAGGCGGCG GGCGCGGCGG GTGGGCTCGG CGGAGGGTGA GGCGGCGGGG CGCCCCGCGG
97380


 


GGAAGGGGCT CCGGAGTGAC GCGGGACCCG GCTAGCGGCG AGCCCACGGC GGCTCGGAAG
97440


 


GGAAGCGCGG AGCCTGAGCG GGGGTACCCG GGCTGCGACC TCTGCGCTGG GAGCTGTGCC
97500


 


TCTGAGCCGG TGTCTCCCCG AGGGAAAGGG GACGTGCCCG TGCCCGTCCC CGCCCTCAGG
97560


 


CTGTGGGGTC GGTCCCGAGA CGCGGGGCTC AGCTGGCTTC TCTTCTTGCA GCCCTGGTCC
97620


 


AGCGCCTCCC TCTCTCAGCA TGGACGAGGA GAGCCTGGAG TCGGCCTTGC AGACCTACCG
97680


 


TGCGCAGCTG CAGCAGGTGG AGCTGGCCTT GGGCGCCGGC CTGGATTCGT CTGAGCAGGC
97740


 


TGACCTGCGC CAGCTCCAGG GGGACCTGAA GGAGCTCATC GAGCTCACCG AGGCCAGCCT
97800


 


GGTGTCTGTC AGGAAGAGCA GGTTGTTGGC CGCGCTGGAC GAAGAGCGCC CGGGCCGCCA
97860


 


GGAAGATGCT GAGTACCAGG CTTTCCGGGA GGCCATCACT GAGGCGGTGG AGGCACCAGC
97920


 


AGCGGCCCGT GGGTCCGGAT CAGAGACCGT TCCTAAAGCA GAGGCGGGGC CAGAATCTGC
97980


 


GGCAGGTGGG CAGGAGGAGG AAGAGGGAGA GGACGAGGAA GAGCTGAGTG GGACAAAGGT
98040


 


GAGCGCGCCC TACTACACCT CCTGGGGCAC TCTGGAGTAT CACAACGCCA TGGTGGTGGG
98100


 


AACGGAAGAG GCGGAGGATG GCTCGGCGGG TGTCCGTGTG CTTTACCTGT ACCCCACTCA
98160


 


CAAGTCTCTG AAGCCGTGCC CGTTCTTCCT GGAGGGAAAG TGCCGCTTTA AGGAGAACTG
98220


 


CAGGTAAAGC CCTTTGTTGT CAGATGCCAA CCTTAGGGGC GTAAGGGGCA CGCACACAGG
98280


 


GTCGGGTCAG GATCGGCCCT CCCTTTGCTT TGCAGTTTTG TCTCAGCTTC CTGGGGCAGG
98340


 


CGTGCTTTGA CAGCTGTGTC TGTGTTCAGG CGTCTACGTC TTCCTTCTGG GGTGAATCAA
98400


 


GAAGCATGGA AGGAGGCCAG GCGCGGTGGC TCACGCCTGT AATCCCAGCA CTTTAGGAAG
98460


 


CCGAGGCGGG CAGATCACCT GAGGTCAGGA GTTCAAGACC ACGCTGGTCA ACATGGTCAA
98520


 


ACCCCATCTC CTTAAAAACA CAAAAATGAA CCGGTCGTGG TGGCGCGCAC CTGTGGTCCT
98580


 


GGCTACTCAG GAGGCTGAGG CAGGAGAATT GGTTGAACCC AGGAGGCCGA GTTTGCAGTG
98640


 


AGTGGAGATG CAGCCACTGT ACTGCAGCCC GAGCAGCAGT GCAAGGCTTA TGTGGAAGAG
98700


 


AGTAGGTCTC CAGCCTATCG TCAGTTTTTT TTTGGTCGTT GTTTTAATTT TTTTTGAGAC
98760


 


AGGGTCTTAC TTTGTCAACC AGGCTGGAGT GCAGTGGCAT AGTCCTGGCT CACTGCAGCC
98820


 


TGGACCTCCT GGGCTCAACC GATCCTCCTG CCTCAGCCCC CCTAGGAGCT GGGCTACAGA
98880


 


CTCACGCTAC TACACCCAGC TAATTTTTAT ATTACTATAA TTTTTTATCT TTTTTTTGAG
98940


 


ACGGAGTCTT GTTCTGTTGC CCAGGCTGGA GTGCAGTGGC GTGATCTCGG CTCACTGCAA
99000


 


GCTCCGCCTC CCGGGTTCAC GCCATTCTCC TGCCTCAGCC TCCCGAGTAG CTGGGACTAC
99060


 


AGGCGCCCGC CACCATGTCT GGCTAATTTT CTGTATTTTT AGTAGAGACG GGGTTTCACC
99120


 


ATGTTAGCCA GGATGGTCTC AATCTCCTGA CCTCGTGATC CGCCCACCTT GGCCTCCCAA
99180


 


AGTGCTGGGA TGACAAGCGT GAGCCACCGC GCCTGGCCTT TTTTTTTTGG AGACAGAGTT
99240


 


TCACTCTCCT CACCCAGGCT GGAGTGTAGT GGCGCAATCT CAGCTTACCG CAACCTCTGT
99300


 


CTCCCGGGTT GAAGTAATTC TCTACCTCAG CGTCCAGAGT AGCTGGCATT ACAGGCGCCC
99360


 


GCCACCACAC TCGGCTAATT TTTTGTATTT TTAGTAGAGT CGGAGATTCA CCATCTTGGC
99420


 


CAGGCTGGTC TTGAACTCCT GACCTCGTGA TCCACCCACC TTGGCCTCCC AAAGTGCTGG
99480


 


GATCACAGGC GTGAGCCACT GCGCCTGGCC CTGTTGTTAG TTTTATTCTC TAGAGTTCAA
99540


 


CTTTTAAATT TTACTTTCAT GGAGATTTTC AAACATACCC CAAATTAGAG AGTTTAGCAT
99600


 


AATCACCGCC CACGGTCCAT CATCCAATGT CGTCATTTAT TAATATTTTC CCAGTCTCAT
99660


 


TTTGTCTGTT CTCCCTGCCC TATTTTTTTC TTTCCTGGGC CATTTTAAAG CAAATTCCAG
99720


 


AAGTTACTGG TTTTTTCCAA TTATGAATAC TTCATAGTTG CATCTCTAAT CTAACTGATT
99780


 


AGGAAATTAC TTAAAAAGTA ACTTTTTGGA AGTCCAAGTC CGATGTGAGG ACAAAAAAGA
99840


 


GTAACTTCTG TGTCATAATA GGTAACACAT TTAATGGTAA TACCTCTTCC ATATTCAAAT
99900


 


ATGAACAATT ATTACTGTAA TGTCTCTATT TCCCTAAGCG CATAGCTTTA TTTTTCCTCC
99960


 


TTTTTACTTT TCTCTTAGAA GAAATATTTA CCAAGCCTTC TAGTAGGTAA TTTTCTTTTT
100020


 


TAGCCAATAG TTCAGGCTGA CCGTGTAACC ATCCCTAGTT CTAGTTCTAG TTCTTTGAAT
100080


 


GTCTTCCTTT TTTTTTTTTT TTGAAACAGC GTCTTGCTGC TCTGTCACCC AGGCTGGAGT
100140


 


GCAGTGGCAC AATCTCGGCT CACTGCAATC TCCGCCTCCC TGGCCCAAGC CATCCTCCCA
100200


 


CCTCAGCCTC CCTAATAGCT GATACTACAA GTGTGCACTG CCACGCCCAG CTAATTTTTG
100260


 


TATTTTTTGT AGAGACGGGA TTTCACCATA TTACCCAGGT CTCGAATTCC TGATCCCTTT
100320


 


GATGAGAGAT CTGACACATC CCTGTGGTGC TCCCTCTGGA CCAGGCACTG CTCCAAGGGT
100380


 


TTCATATACT TTCATTCATC TGTGCAACAG CCCTGTAGGT AGGCCCTGCA GTCACACCAT
100440


 


CTGACAGAGG AGGAAACAGG AGTAGAAGAA CTGAGTGGTC CAGGGCTTCA AGGCTCAGAG
100500


 


GGCTCCAGTT GCCCCCAGCC CTCGTTCCGT CCCCTGCTCC ACCCAGTGCT GCTTGCCATG
100560


 


TCGGCATCAG GCCTGATCTG AAAGCTTCCG GAGCATCTTA CAGACGTCCA CCTTCCCACC
100620


 


ATTCAGGACT GATAAGTTCT CTTGGATTTG CGTTGGACCT TTTTTTTTTT TTTAAGATGG
100680


 


AGTTTCACTG TTGTTGCCCA GGCTAGAGTA CAATGGCACG ACCTCCACCT CCTGGGTTCA
100740


 


AGGGATTCTC CTGCCTCAGC CTCCCAAGTA GCTGGGATTA CAGGCGCCTG TCACCACGTG
100800


 


GTGCCCAGCT AATTTTTATA TTTTTAGTAG AGGCAGGGTT TCACCGTGTT GGCCAGGCTG
100860


 


GTCTCGAACC CTTGACCTCA GGTGATCCCG CCTTGGTTTC CCAAAGTGCT GGGATTACAG
100920


 


GCATGAGCCA CCACACCCGG CCCAGGATTT CTTTATATAT TCTGGATATC ATCCCTTATG
100980


 


AAGTATATAG TTTGCAGATA TTTGCTCCCA TTGTTTGGGT TGTCTTTTCA CTTGATATAG
101040


 


TGTCCTTTGA TGCACAAACA TTTTAAATTT TGATGCAGTG CAATTTATTG TTTCTTTATT
101100


 


GCCTATGTTT TTGTCATCAG GTTTAAGAAA CCACCTCATC CATAGTTATG AGGATTTTCA
101160


 


CCTATGTTTT CTTCTAAGAG TTCTGTAGTT TTAGCTGTTA AATTTAGGTC TTTGATCCAT
101220


 


TTTGAGTTAA TTTTTGTATA TGTTATTAGG TGAGGGTCCA CTTTATTCTT TTGCATGTGG
101280


 


ATTTCCAGTT TTCCCAGCAC CATTTGTTTA AAAGACTGCT TTTTCTCCAC TGAATGGTCT
101340


 


TGGCACTTTT GTCCAAAATC AATTGGCAAT ATATGTAAGG GTTTATTTCT GAGCTCTCTC
101400


 


TCCTGTTCCA TTGGTGTATA TGTGCCAGTA CCACACTGTT CTGATTATTA TAGCTTTGTG
101460


 


ATAAGTTTTA AACTCAGGAA GTGGTAGTTA TTCACCATTT GCTCCTCTTT TTCAAGTTTG
101520


 


TTTTGTTTCT GGATCCTTTG CAATTTCATA TGAATTTTAG GATCGGCTTG TCCAATTCTG
101580


 


CATAAAAGAC AGTTTGAATT TTGATATGGA TTGCATAGAA TGTGTAGATC TGTTTGGGGC
101640


 


ACATTGTCAT CTTTACAATA TTAAGCCTTC TGGCTGGGTG TGGTGGCTGA CGCCTGTAAT
101700


 


CCCAGTACTT TGGGAGGCTG AGGCGGGCAT ATCACTTGAG GTCAGGAGTT CAAGACCAGC
101760


 


CTGGCCAACG TGGTGAAACC CCGTCTCTAC TAAAAATAAA AAACAAATTA GTCGGAGGTG
101820


 


GTGCACACCT GTAATCCCAG CTACAGGAGA GGGTGAGGCA GGAGAATCGC TTGAACCTGG
101880


 


GAGGAGGAGG TTGCAGTGAG CTGAGATCAT GCCACTGCAC TCCAGCCTGG GTAACAGAGG
101940


 


GAGACTCCAT CTTAAACAAC AACAATAACA GAAGAAAAAA ACAGTATTAA GTCTTCCAAT
102000


 


TCATGAATGA AGGATCTGTC CATTTATTTA CGTCTTTAAT TTCTTTCAAC AGTATTTTGT
102060


 


ACTGTTCAAG TCTTGCACAT TCTTGGTTAA ATAAGTATTA TTTTTGATGC TTCTCTAAGG
102120


 


AATTGTTTTT CTTTTCCTTT TTTTTTTTGA GACAGAGTCT TGCTCTGTCA CCCAGGCTGG
102180


 


AGTGCAGTGG CACAATCTTG GCTCACTGCA ACCTCTGCCT CCCGGGTTCA AGCAATTCTT
102240


 


CTGCTCACCC TCCCAAGTAG CTGGGATCAC AGGTGCCTGC CACCACACCC AGCTAATTTT
102300


 


TTTTTTTGAG ATGGAGTCTT GCTCTGTTGC CCAGGCTGGA GTGAAGTGGC CCAATCTTGG
102360


 


CTCACTGCAA GCTCCACCTC CCGGGTTCAC ACCATTCTTC CGCCTCAGCC TCCTGAGTCG
102420


 


CTGGGAATAC AGGTGCCTGC CACCACGCCC AGCTAATTTT TTGTATTTTT AGTAGAGATG
102480


 


GGGTTTCACC ATGTAGCCAG GATGGTCTCG AACTCTTGAC CTCAGGTGAT CTGCCTGCCT
102540


 


CGGCCTCCCA AAGTGCTGGG ATTACAGATG TGAGCCACTG TGCCCGGCTC GAGTTGTTTT
102600


 


CCTTAGTTAC ATTTTCAGGC TGTTTGTTGC TAGTATATAG AAATACAAGC TGGGCACCGT
102660


 


GGCTCACGCC TGTAATCCCA GCACTTTGGG AGGCCAAGGC GGGTGGATCA CCTGTGGTCA
102720


 


GGAGTTCGAG ACCAGCCTGG CCAACATGGT GAAATCCAGC CTCTATTAAA AATACAAAAA
102780


 


TTAGTCTGGC ATGGTGGCAG GTGCCTGTAA TCCCATCTAC TCAGGAGGCT GAGGCAAGAG
102840


 


AATTGCTTGA ACCTGGGAGG CGGAGGTTGC AGTGAGCTGA GATCGCGCCA TTGCACTCCA
102900


 


GCTTGGGGAA CAAGAGTGAG ACTTCATCTC AAAAAAAAAA AAAAAGAAAT ACAGTGGATT
102960


 


TTTTTATGTT AATCCTGTAT TGATTGCTGA ATTGGTTTAT TAGTGCTAAT AGGATTTTTT
103020


 


ATGCACTATT TAGGATTTTC GATATATACA ATCATATATA TTCAATATAT ACAATTAATA
103080


 


TATATGTGAA TAGAGATAAT TGTAGTCTTT GTTTCTAGTT TGCATGGCAT TTATTTCTTT
103140


 


TTCTTGCTTA ACTGCCTTAG CTAGAACTTC AAGTACGATG TTGAATAAAA GTGACTAGAG
103200


 


CGGGCCGGGG GTGGTGGCTC ACACCTGTGT TCCCAGCACT TTGGGAGGTG GAAGTGGGCA
103260


 


GATCACTTGA GATCAGCAGT TTGAGACCAG CCTGGCCAAC ACGGCGAAAC CCCATCTCTA
103320


 


CTAAAAATAC AAAAATTAGC TGGGTGAGGT GATGTGCACC TGTAGTCCCA GCTACTTGAG
103380


 


AGGGTGAGAC ATGAGAATTG CTTGAACCTG GGGGGCGGAG GTTGCAGTGA GCCAAGATCA
103440


 


TGCCACTCCA CTCCAGCCTG GAGGACAGAG CAAGAACCCT GTCTTTAAAA AAAAAAAAAA
103500


 


AAAAGTGGCT AGAACAAACA TCTTTATCTT GTTCCTGATC TTAGGTGGAA AACTTTTTTG
103560


 


TTCCTGATAT TAGGTGGAAA ACTTTTAGTC TTTCACTGTT GAATATGATG TTACTTGTAG
103620


 


GTTTTCTGTA GATTCCCTTT ATCGAGTTGA GGAAATTCTC TTATATTCAT AGTGTGTTGA
103680


 


GTGTTTTTTA TCATGAAAGG GTGTTGATTT TTTTTTTAAA GATAGGGTCT TGTTCTGTCA
103740


 


CCCAGGCTGG AGGGCAGTGG CATGATCATG GCTCACTGCA ACCTCGAATT CCTGGGCTCA
103800


 


GGGGATCCTC CTACTTCATC CTCCTGAGTA GGTGAGACTA CAGGCATGAG CCACCATGCC
103860


 


CAGCTAATTT TTTAATTTTT CTGTAGAGGT AGGGTCCTGC TTTGCTGCCC AGGCTGGTCT
103920


 


TAAACTCCAG GGCTCAAGCA ATCCTGCCTC AGCCTCCCAA AGTGCTGAGA TTACAGGGGT
103980


 


GAGTCACTGC ACTGCACCCA GCTGTGTGGG ATTTTTCAAA TGCTTTTTTC CTTTAGATGA
104040


 


TCATGTGTGG TTTTTTTCCT TTCATTTTGT TAATGTGGTA TATTGATTTT CGTATGTTGA
104100


 


ACCATCCTTG AATTCCTCAG ATAAAGCACG CATATTCATG GCGTATTATC TCTTTATTAT
104160


 


TATTTTTTTT GTAGAGATGA GATTTCACTC TGTTGCCCAA GCTGGTCTCA AACTCCTGGG
104220


 


CTAAAGTGAT CCTCCTGCCT CAGCCTCCGA AAGCGCTGGG ATTATAGGCA TGAGCCACTT
104280


 


GGCCCTATCT TTTTTCTTTT TCTTTTTTTT TTTTTTTTGA GACAGAGTCT CACTCTGTCG
104340


 


CCGGGCTGGA GTGAGTGGCG CGATCTCGGC TCACTGCAAC CTCCATCTCC CGGGTTCAAG
104400


 


CAATTCTCCT GCCTCAGCCT CCTGAGTAGC TGGGACTACA GGTGCCCGCC ACTATGCCCA
104460


 


GCTAATTTTT TGTGTTTTTA GTTGAGACGG TGTTTTGCCA TGTTGGACAG GCTGGTCTTG
104520


 


CACTCCTGAC CTCGTGATTC ACCCACCTTG GCCTCCCGAA GTGCTGGGAT TACAGGCATG
104580


 


AGCCACCGCA GCGAGCCTTA TCTTTTTAAC AGTTAAAAGT TTAAGGCCTT ATCATGTAAT
104640


 


AACATTGCTG GATTTGATTT GCTGCTGTTT TGTTGAGAAT ATTTGCATCT GTATTGATAA
104700


 


GGGATATTGG TCTGTAGTTT TCTTTTCTTG GCATGTCTTT GTATAGCTTT GATGCCAGCA
104760


 


TAATATTGGC CTCATAGAAT GAGTTAGGAA GTATTCTTTA TATTATGGGA AGAGGTAAAA
104820


 


AGGGATTGGT GTTAATTCTT CTTCAAATGT TTGATAGAAT TCAACAGTGA AGTGATATAT
104880


 


ACAATCATAT ATATAGAGAG AGAGAGAGAG AGAGATGGAC TTTTCTTTTG TTGGAAGTTT
104940


 


ATTGACTATT GATTCAATTT CCTTATTGAA ATTGACTTTT CTTTTTGGAA GCTAAAATGT
105000


 


ATAACTGTAG TGAAAGTTTC TGAACTTTTC TTTCATTGGA AGTTTTTTGA CTACTGATTC
105060


 


TTTATTTGTT ATAGGTCTAT TCAGATTTTC TGTTTCTTCT TGAGTCAGTT TGGTCTCGCT
105120


 


CTGTCGCCCA GGCTGGAGTG CAGTGGTGCC ATCTTGGCTC ACTGCAACTT CTACCTCCCG
105180


 


AGTTCAAGTG ATTCTCCCAC CTCAGCCTCC CCAGTATCTC GGACTACAGG CGCACGCCAG
105240


 


CATACCTGGC TAATTTTTGT ATTTTTAGTA GGAACAGCAT TTCACCATGT TGGCCAGGCT
105300


 


GGTCTCGAAC TCCTGACCTC AGGTGATCCA CCCGCCTCGG CCTCACAAAG TGCTGGGACT
105360


 


ACAGACATAA GCCACCGCGT CCAGCCTTGA GTCAGTTTAG ATAGTTTGCA TGCATGTTTC
105420


 


TAGGAATTTG TCCATTTTGT TTATGTTATC TAATCTGTTA CCATACAATT GTTCATAGTA
105480


 


TCCTTTTATA GCCCTAGTTA TTTCTGTAAG ATCAGTAGTA ATAGCTCCAC TTTCTCTCTT
105540


 


GGTTTTAGCA ATTTGAGTCA TCTCTTTTCT TCTTCTTTTT TTTTTTTTGA GATGGAGTCT
105600


 


CACTGTGTCA CCCAGGCTGG AGTGCAGTGG CATGATCTTG GCTCACTGCA ACCCCTGCCT
105660


 


CCCAGGTTCA AGCAATTCTG CCTTAGCCTC CTGAGTAGCT GGGATTACAG GTGTGAGCCA
105720


 


CCACACCCAG CTAGTTTTGT TTTGTTTTTT TGTTTTTGAG ACGGAGTCTG TTTCTGTCTC
105780


 


CCAGGCTGGA GTGCAGTGGT GCAATCTCAC TCATTGCAAC CTCCGACTCC CAGATTCCAG
105840


 


CAATTCTCCT GCCTCAGCCT CCCGAGTAGC TGGAACTATA GGCGTGCACC ACCACGCCTG
105900


 


GCTGATTTTT ATATTTTTAG TAGAGATGGG ATTTCACCAT GTTGGCCAGG CTGGTCTTGG
105960


 


ACTCCCTACC TGAGGTGATC CGCCCACCTT GGCCTCCCAA AGTGCTGGGA TTATAGGCAT
106020


 


GAGCCACCAT GCCCAGCCAG TTTTTGTATT TTTAGTAGAG ATGGGGTTTC TCCCTGTCGG
106080


 


CCAGGCTGGT CTTGAAATCC TGACCTCAGG TTATCCACCA GCCTTGGCCT CCCAAAGTGC
106140


 


TAGGATTACA GGCATGAGCC ACCACGCATG GCCTGTCTTT TCTTCTTGGT CATTTTCGCT
106200


 


AAAGGTTTGT CAATTTTGTT GATCTTTTTT GTTGCTGATC TCTATTGTTT TCCCATTCTG
106260


 


TTTCATTTAT TTCCATTTTA ACCTTTGTTT CCTTTTTTCT GCTGGTTTGG GTTTAATTTG
106320


 


CTCTTTTTTT CCCCTAATTT TTCAAGGTAT ACAGTTAAGT TATTGATTTG AGATCTCTTT
106380


 


TTTCTTTTCT TTTTTTTTTT TTTTTTTTTT TTTGGTTGCT GTTGAGATGG AGTCTCCCTC
106440


 


TGTCACCCAG ACTGGAGTGC AGTGGCATGA TCTCAGCTCA CTGCAGCCTC CGCCGCCCAG
106500


 


GCGATTCTCC TGCCTCAGCC TCCTGAGTAG ACGTTTCCCG GCCAAGGTGT TTCTTTTTGA
106560


 


ATGTAAGCAT TTACAGCTAC AGATTTCCCT CTAAACACTG CTTTCACTGC ATTCCATAAG
106620


 


ATTGTTTTTT GTTGTTTTTT GTTGTTGTTT TGTTGTTTGA GACACAGTCT CACTCTGTTG
106680


 


CCGTTTGGAG AGCAGCGATG CGATCATAGC TCTGTAGCCT TGAGCTCCTG GACTCAATCA
106740


 


GTCCTCCTGC CTCAGCCTCC CAAGTAGCTG GGACTACAGG TGTACACCAC TGCACCTAAC
106800


 


TAATTTCTTT TATAAGTTTT TGCAGAGGCC AGGCACAGTG GCTCACACCT GTAATCCCAG
106860


 


CACTTTGGGA GGCCAAGGTG GGTGGATCAC CTAAGGTCAG GAGTTCGAGA CCAGCCTGGC
106920


 


CGACAGGGAG AAACCCCATC TCTACTAAAA ATACAAAAAT TAGCTGGGCG TGGTGGCAGG
106980


 


TGCCTGTAAT CCCAGCTACT CAGGAGGCTG AGGCAGGAGA ATCGCTTGAA CCTGGGAGGC
107040


 


AGAGGTTGCA GTGAGCCAGG ATCACACCAT TGCACTCCAG CCTGGGTAAC AAAAGCAAAA
107100


 


CTCCATCTCA AGAAAAGAAA AAAAAAAGTT TTTGCAGAGA CAGGGTATCA CTTTGTTGCC
107160


 


CAGGCTGGTC TCAAACTCCT GACTTGAAGG AGTCCTACTG CCTCAGCCTC CCAAAGTGCT
107220


 


GAGATTATGG GCAAGAGCCA CCGCACCCTG CCACTTGGCT GTTTTGTTCT GTTGTATTTC
107280


 


CATTTTCATT GATCTCAAGA CATCCTAATC TCCCTTTTGT TTTTTTGTTC GACTTACTGG
107340


 


TTATTCAAGA GTGTCTTTAT TTCTGCATAT TTGTAAATTT TCCAAAAAAG TTTTTCTTTC
107400


 


TTTTTTTTTT GAGAAAGGGT CTTGCTCTGT CGCCCAGGCT GGAGAATGGT GGTGCACAAT
107460


 


CTTGCCTCAC TGCAACCTCT GCCTCCCGGG TTCAAGTGAT CCTCCCACCT CAGCCTTCCC
107520


 


AGTAGCTGGG ATTACAGGCA CACACCACCA CACCTGGCTA ATTTTTGTAT TTTAGTCTTA
107580


 


ACGTGCTGGT CAGACTGGTC TCGAATTCCT GACCTCAGGT GATCTGCCCG CCTTGGCCTC
107640


 


CCAAAGCACT GGGATTACAG GCGTGAAACA CCATGCCCAG CCCCCAATTT TTTTTTTTTA
107700


 


ATAGAGAGAA GGTCTCACTC AAGCCCAGGC TGGTCTTGAA CTCCTGAGCT CAAGCTGTCA
107760


 


TCCCTCCTCG GCCTCCCAAG GTGCTGAGAT TACAGGTGTG AGTCACAGTA CCTGGCCTTC
107820


 


TTTCAAGACT TTAAAAATGC CATCTTGGCT GGGCACGGTG GCTCACGCCT GTAATCCCAG
107880


 


CACTTTGGGA GGCCGAGGTG GGCAGATCAC GAGGTCAGGA GATCAAGACC ACCCTGGCTA
107940


 


ACATGGTGAA ACCCTGTCTC TACTAAAAAT ACAAAAAATT AACCAGGTGT GGTGGCAGGT
108000


 


GCCTGTAGTC CCAGCTACTC GGGAAGCTGA AGCAGGAGAA TGGCGTGAAC CCGGGAGGTG
108060


 


GAGCTTGCAG TGAGCTGAGA TCACACCACT GTACTCCAGC CTGGGCAACA GTGCGAGACT
108120


 


CCGTCTCAAA AAAAAAAAAA AAAATGTCAT CTCACTGCCT TCTGGTCCAA TAGTTTCTGA
108180


 


TGAGAAATTG GCTGTTAATC TTATTGAGGA ACATTTATAT ATTGACTAGT CACTTGTCTC
108240


 


TTGCTGTTTT AGGAGATTCT CTATCTTTGG GTTTCAGCAG TTTGATTATA ATGTATCAGT
108300


 


GTGGATCCCT CAATTTATAA GCTACTTGGA GTTCATTGGA CTTCTTGGAT GTGTAAATTC
108360


 


ATGTCTTTCA TTAAATTTGC AAAGTTTCAG CTACTATTCT TTGCATCTTG AAATACTAGT
108420


 


TTTGTTTCTT TCTGTCTGTT TGCCGCTTAT GGAACTTTAT GCATACATTG ATGTGCTTCA
108480


 


TGGTGTAGCA CAGGTCCCTT GGGCTCTAGG CATTTTTCTT TGTTCTTTTT TTCTTTCTGC
108540


 


TCCTCATTTT GGATAAATTC AGCTGACCTG TCCTCAAGTT CACTGTTTCT TTCTTCTTCC
108600


 


TTCTCAAATC TGCTGTTGAA ACTTCTGGTG AAATTTTCAC TACAGTTACT GTACTTTTTA
108660


 


GCTCCAAAGT TTCTATTTGG TTTCTTTCTG TAGTAATTAT CACTTTACTA GTATTCTCTA
108720


 


TTTGGTTACA CATGGTTCTT TTGTTTTCCT TTAGTTCATT ATCCATGGTT TCCTTTATTT
108780


 


TTAAATTTCT TTTTATTTAG TTATTAATTT TTTTTTTTTT TGAAGCGGGG TTTCACTCTT
108840


 


GTCACCCAGG CTGGCAGGCA ACGTCACAAT CTTGGCTCAC TACAACCTCC GCCTCCTGGG
108900


 


TTCAAGTGAT TCTCCTGCCT CAGCCTCCCA AGTAGCTGGG ATTATAGGCA TGTGCCACCA
108960


 


CACCCACCTA ATTTTTGGTA TTTTTAGTAG AAACTGGGTT TCACCACATT GGCCAGACTG
109020


 


GTCTTAAACT ACTAACCTCA GGTGATCTGT CCGCCTCAGC CTCCCAAAAT GCTGGGATTA
109080


 


CAGATGTGAG CCACTGTGCC CAGCCTCTTT TTTTAGTGTA TTTAAGGTAA TTGATTGAAA
109140


 


GTTTTTGTCT AGTCATTCAA ATGTCTAGGC TTCCTCAGGA ACAGTTTCTA TTAATTTCTT
109200


 


TATTTTTAAA AAATTTTTTT TAATTTTCTT TTTTTTTTAG ATGGAGTCTC ACTCTATAGC
109260


 


CTAGGCTGGA GTGCAATGGC TTGATCTTGG CTCACTGCAA CCTCTGCCTC CTGGGTTCAA
109320


 


GCGATTCTCC TGCTTCAGCC TCCTGAGTAG CTGGGACTAT AGGTGCGTGC CACCACTCCT
109380


 


GGCTAATTTT TTGTATTTTC AGTAGAGACA TGGTTTTGCC GTGTTAGCCA GGATGGTCTC
109440


 


GATCTCGTGA CCTCATGATC CTCCTGCCTC GGCCTCCCAA AGTGCTGGAA TTACAGGTGT
109500


 


GAGCCACCGC GCCCAGCCTA TTTTTTATTT TTTGAGACAA AGTCTCCCTC TCTCACCCAG
109560


 


GCTGTAGTGC AGTGGCACAA CCCTGGCACA CTGCAGCCTT AACCGTCCAG GCTTAAGTGA
109620


 


GTCTCCCACC TTAGTCTCCT GAGTAGCTAG AACTACAAGC ATGTGCCACC ATGCCTGGCT
109680


 


GGTTGTGTTG TTACTGTTTT AGACACAGGG TCTTGCTACA TTTCTCTGAC TGGTCTTGAA
109740


 


CTCCTGGGCT CAAGCAGTCA TCCCACCTTG GCCTCCCAAG GTGTTGAGAT TACAGGTGTG
109800


 


AGCCACCGCA CCCGGCCTGT TAATTTCTTT ATTTCCGGTG AATGGGCCAC ACTTTCTTGT
109860


 


TTCTTTGCAT GCCTTGTAAT TTTTTGTTGA AACCTGCACA ATTTGAAGAT GATAATGTCG
109920


 


TTACTTTGAA AATCAGATCC TCCGCCCTCT GCAGGGTTCA TTGTTGCTGT TTGTTGTGGA
109980


 


TTGTCGTTTC TCGTTTGTTT AGTTACTTTC CTGACCTTTT TAAATAAAGA CTATATTCTG
110040


 


TCAGGGGTGC TTGTTTCTGT TCTTTTAGGT TAGTGGTTAG CTTGTGCTTT GAAAGAGATT
110100


 


TCTTTAAATA TCTAGTGGCA AAAAGGATAA AGAGGCCGGG CGCAGTGGCT CACGCCTGTA
110160


 


ATGCTAGGAC TTTGGGAAGT GGAGGCGGGT GGATCACTTG AGGTCAGGAG TTTAAGATCA
110220


 


GCCTGGCCAG TATGGTGAAA CCCTGTCTCT ACTAAAAATA CAAAAATTAA CCGGGCATGG
110280


 


TGGCACCTGC CTGTAGTCCC AGCTACTGGG AAGACTGAGG CAGGAGAATC GCTTCAATCC
110340


 


AGGGGGCGGA GGTTGCAGTG AGCTGAGATT GCGCCATTGC ACTCCAGCCT GGGCAACAGA
110400


 


GCGAGACTCT GTCTCAAATA AAAAAAAAAA AAAAAGGATA AAGAGTGTCT TCCATCCTTT
110460


 


CCAGGTTGCC TCTGTACTGG GGCAAGTCCT TCAGTGTCCG CCAGGCTGTT CACGGCTTTT
110520


 


CCTCAGCCTT TACTTCTCGC TCCCATGGAG CCTAAGGATG AACCAGAGGT GAAAGTTGAG
110580


 


GGCCTCCTCA GGTGTTTCTG AGCCCCTGTC TAGCCCCAGC TGTGTGCATG GCCTTCTGGA
110640


 


TTTCCAAGCA TGAACAGGAG CTTTCCAAAG CCCTTAGACC TTCATGTAGC TCTTTTCCCA
110700


 


GCCTCTTCCT TCCTAGGCTT TTCTGTCAGC TCTTTGCCCA TCTGTTGTTG TCCCTCCCCC
110760


 


ACAACTTCAG GTAGTATCTA CCTGTAAATG CCTTCAGGCC AGGCGCGGTG GCTCATACCT
110820


 


GTTATCCCAG CACTTTGGGA GGCCGAGGCG GGTGAATTGC TTGAGGTCAG GAGTTCGAGA
110880


 


CCAGCCTGGC CAACATGGTG AAGCCCCGTC TCTAGTAAAA ATACAAAAAT TAGCTGGGCG
110940


 


TGGTGGGTGC CTGTAATCTC AGCTACTCGG GAGGCTGAAG CAGGAGAATT GCTTGAGCCT
111000


 


GGGAGGCGGA GGTTGCAGTG AGCTGAGATC GTGCCATTGC ACTCCAGCCT GGGCGACAGA
111060


 


GTGAGACTCC ATCTCGGGGA AAAAAAAAAA AAAAAAATGC CATCAACAGC ACGACCCTGG
111120


 


AGGCTGCCCC AGCCCTGAGA GAGTTCGAGG GGGTGAAACA AACGCAAGCC CTTCAGGGAG
111180


 


ACACTAGAAA GATCCAAATC CATAAGCAGG ATTCCTTGAG AAAAGGTCTG TATCATCCCT
111240


 


TCTGACACCA GCAAGCCACA TCAGAAATAC AGGTTGCCTT CCCCATGGCT ACATGTGAGC
111300


 


TGGTAGTAGT GGCTGAGCAG AAATAGCCCA GCTGTCCTCC TGAAATTTAG CAGGGTCTTA
111360


 


CTTCATTGAG CAGTCATCTG GTTCGTAGAC ACCAGAGTTA CAGAAAAGTT TATTGGGAGG
111420


 


TTTTGACAGT TTAATAGAAA AAAGTTTATT GTGACAGTTT TGACAGCTGA ATAGAAAAAA
111480


 


GTTTACTGTG ACAGTTTTGA CAGCAGAATA GTTGCTTTGC TGGAGAGACG GATCTTTGGA
111540


 


GCTGCCAACT CCATCATTTT GGTGATATCC AGCTCTGTTG CTGAATTTTT AGCTATGCTG
111600


 


TTTTAAGTTA TTTTCTTAGT GGTTGCTCTA GAGATGACAA TGTGCATCTT TAACTTACCA
111660


 


CAATGTACTT CAGATTATTA CTAACTTAAC ACTTAAAGTA CAGCATTTTT TTTTTTATGG
111720


 


AGTTTCACTC TGTCACCCAG GCTGGAGTGC AATGGTGTGA TCTCGGCTCA CTGCAACCTC
111780


 


CGCCTCCCAG GTTCACGCCA TTCTCCTGCC TCAGCCTCCT GAGTAGCTGG GACTACAGGC
111840


 


ACCCCCACCA CACCCGGCTA ATTTTGTATT TTTAGTAGAG ATGAGGTTTC ACCATGTTGG
111900


 


TCAGGCTGGT CTCGAACTGC TGACCTCAGG TGATCCGCCC ATCTTGGCCT CCCAAAGTGC
111960


 


TGGGATTACA GGTGTGAGCG ACTGCACTGA GCCTAAGTAT GGCAACGTGT CTATAACATA
112020


 


GATCTACTTC CGTTGTACTA TGACATAGTT CCCCCTCCAT TTTCCTATAG CACAGTCCCA
112080


 


ACCTCCCTTT TCCTCTGACA TAGTTCCATC CTCCCTCCTC CTATGACGTC CTCCCTTCTC
112140


 


CTCTGGCATA GCTCCATCCT CCCTTCTCCT ATGACACAGC TCCATCCTCC CTTCTCCTCT
112200


 


GACACAGCTC CATCCTCCCT TCTCCTATGA CACAGCTCCA TCCTCCCTTC TCCTCTGACA
112260


 


TAGCTCCATC CTCCCTTCTC CTATGTCATA GCTCCATCCT CCCTTCTCCT CTGACACAGC
112320


 


TCCATCCTCC CTTCTCCTCT GGCATAGCTC CATCCTCCCT TCTCCTATGA CACAGCTCCA
112380


 


TCCTCCCTTC TCCTATGACA CAGCTCCATC CTCCCTTCTC CTATGACACA GCTCCATCCT
112440


 


CCCTTCTCCT ATGACACAGC TCCATCCTCC CTTCTCCTCT GGCATAGCTC CATCCTCCCT
112500


 


TCTCCTCTGA CATAGCTCCA TCCTCCCTTC TCCTCTGACA TAGCTCCATC CTCCCTTCTC
112560


 


CTCTGACATA GCTCCATCCT CCCTTCTCCT CTGACATAGC TCCATCCTCC CTTCTCCTCT
112620


 


GACATAGCTC CATCCTCCCT TCTCCTCTGA CATAGTTCCA TCCTCCCTTG TCCTCTGACA
112680


 


TAGCTCCATC CTCCCTTCTC CTCTGACATA GCTCCATCCC CTCTTCTCCT TCATGTATTA
112740


 


TTGCCATATA TACATTTATG TATGTTATAA CTTCAGCTCT TCAGCGTTAT AATTATTGCT
112800


 


TCAAAAGTAT TTTGAAAGAA GTTGCCTGGA GGCACTGGCT TATGCCTTTA ACTCCAGCAC
112860


 


TTTTGGGGGC TGAGGTGGGC AGATCGCCTG AGCCAGGGAG TTGGAGACCA GCCTGGGCAA
112920


 


CATGACGAAA CCCATCTCCA CCAAAATTAC AAAAAATTAG TCTGGCATGG TGGCACGCGC
112980


 


CTGTAGTCCC AGCTATTTGG GGGAGGATCC CAGCTAAGGT GGGAGGATCA CTTGAGCCTG
113040


 


GGAAGTCAAG GCTGCAGTGA GCTGAGATTG TGCCACTGCA CTCCAGCCTG GGTGCAGATC
113100


 


TTATCTCAGA AGTAAAGGGA CTAGGAATGG TGGCTTTTAT CTCTAATCCC AGCACTTTGG
113160


 


GAGGCTGAGG TGAGTGGATC ACCGGAGGTC AGGAGTTTAA GACCAGCCTG GCCAACATGG
113220


 


TGAAACCCCG TCTCTACTAA AAATACAAAA AGTAGCCGGG TGTGGTGGTG GGTGTCTGTA
113280


 


ATCCCAGCTA CTCGGGAGGC TGAGGCAAGA GAATCGCTTG AACCTGGGAA GCGGAGGTTG
113340


 


CAGTGAGCAA GATCGCACCA CTGCATTACA GCCTAGATGA CAGAGCGAGA CTCTGCCTAA
113400


 


AAAAAAAAAA AAAAAGAAAA GAAAAGAAAT TAAGATCTAG ACACTGTGGT TCATGCCTGT
113460


 


AATCCCAAAG CCTTGGGAGG CCAAGGCAGG AGGATCACTT GAGGCCAGGA GTTCAACACC
113520


 


AGCCTGGGCA ACATAGCGAG ACTCCATCTC TATTTAAAAA AGAAAGAAAT TCAAAGAGAA
113580


 


AAAAAGTATA CTTGTTTTTT TGTATCATCC ATATTTTACC TTTCTTTTTT TTGCCCCTTT
113640


 


TTCTTTCCTG TGAATTTGAG TTACTGTCTA GTGTCATTTC CTTTTAGTCT GAAGAACTTC
113700


 


ATTTAGAATT TTTTTTTTTT TTTGAGACAA AGTCTCACTG TGTTGCCCAG GCTGGAGTGC
113760


 


AATGGTGCAG TCTCAGATCA CTGCAACCTC TGCCTCCCTG GTTAGAGTGA TTTTCCTGCC
113820


 


TCAGCCTCCC AAGTAGCTGA GACTGCAGGC ACCTGCCACC ACCCCCAGCC AATTTTTTTG
113880


 


GTATTTTTAG TAGAGACAGG GTTTCACTAT GTTGGCCAGG CTGGTCTCGA ATTCATGACC
113940


 


TCATGATCTG CCTGTCCTGG CCTCCCAAAA TGCTGGGATT ACCATGAGCC ACCACGCCCA
114000


 


GCCCATTTAG AATTTCTTTT TTTTTTTTTT TTTTGAGATG GGGTCTCGCT CTTGTTTCCC
114060


 


AGGCTGGAGT GCAGTGGCAC GATCTCGGCT CACTGCGAGC TCCGCCTCCC GGGTTCACGC
114120


 


CATTCTCCTG CCTCAGCCTC CCGAGTAGCT GGGATTACAG GCGCCTGCCA CCACGCCCAC
114180


 


CTAATTTTTT GTATTTTTAG GAGAGATGGG GTTTCACCAT GTTAGCCAGG ATGGTCTTGA
114240


 


TCTCCTGACC TCGTGATCCG CCCGCCTTGG CCTCCCAAAG TGCTGGGATT ACAGGCGTGA
114300


 


GCCACCGCGC CCGGCTAGAA TTTCTTGTAG GACAGGCTTG CTAGCAACCA ATTCAGTGTT
114360


 


TATTTGGGAA TGTCTTTATT TCAGCTTCAT TTTTTGAAGG ATAGTTTAGC TGGCTATAGA
114420


 


ATTATTAATT GATCATTCTT TTCAGTGTTT AAAAGTGTCA TCATGCTACC TTCTGGGTTC
114480


 


CATTGTTTCT GATGAGAAGT CATCTGTCAA ATTGTCCCTT TGTACTTGAA GAATTATCTT
114540


 


TTTTTCTCTT GATGTTTTCA AGATTTTCTC TTTGTCTTTG GCCTTTAGTA GTTTGTGATG
114600


 


TATCTAGGTG TGGATCTCTT GGTGTGCATC GTATTTGGGC TTCAGTAAGC CTCTTAGATT
114660


 


CATAGATTAA TGTTTTGTTT TGTTTTACCA AATTTGGAGA GTTTTTACTC ATCATTTCAA
114720


 


CAAATTTTTT TCCTGCCCCT CTCTCATCTC CTTTTGGGAG TACCACTGCA TGTATGTTGG
114780


 


TGTGCGTTCT CTA.
114793






The present invention also relates to a portion of SEQ ID NO:3 which comprises 5′ regulatory regions, exons, introns and 3′ non-translated regions which comprise the human NHL gene of the present invention. Such regulatory sequence may be found within the various regions of this 115 kb fragment. The 5′ portion of SEQ ID NO:1 begins at nucleotide 47095 of SEQ ID NO:3, the initiating ATG of human NHL is from nucleotide 48687-48689 of SEQ ID NO:3, the termination ‘TAG’ codon is from nucleotide 84855-84857, while the 3′ terminus of SEQ ID NO:1 as disclosed herein (GCAGTGCCC) corresponds to nucleotides 85308-85316. To this end, one preferred aspect of the invention is an isolated genomic fragment or fragments which comprise from about nucleotide 470000 to about nucleotide 85500 of SEQ ID NO:3), which comprises the portion of the genomic clone encoding the mRNA transcript responsible for human NHL (see FIG. 5A-B). The genomic sequence encoding NHL contains 35 exons (FIG. 5A). An especially preferred aspect of the invention is a human genomic fragment or fragments which comprise from about nucleotide 47095 to about nucleotide 85316 of SEQ ID NO:3. As noted in regard to SEQ ID NO:1, the present invention also relates to DNA vectors and recombinant hosts which comprise at least a portion of SEQ ID NO:3. Portions of the 115 kb genomic fragment may be housed in multiple vector/hosts so as to optimize handling of the DNA sequences within SEQ ID NO:3. Therefore, the present invention relates to the isolated genomic sequence which set forth as SEQ ID NO:3, a region of SEQ ID NO:3 which contains the coding and non-coding region of human NHL, as well as cis-acting sequences within SEQ ID NO:3 which effect regulation of transcription of one or more of the genes localized within this 115 kb human genomic fragment, including regulatory regions effecting levels of NHL, M68/DcR3, SCLIP and ARP. As noted above, this region of chromosome 20 (20q13.3) is associated with tumor growth. Therefore, an aspect of this invention also comprises, as one example, the use of one or more regulatory regions of this 115 kb genomic sequence as a target to antagonize the effect of a transcriptional factor(s) which normally upregulate expression of a gene which has a caustic role in tumor growth. Alternatively, compounds may be selected which interacts with a specific cis-acting sequence to upregulate a gene within this region, where upregulation results in a decrease in tumor growth.
The present invention is also directed to methods of screening for compounds which modulate the expression of DNA or RNA encoding a NHL protein. Compounds which modulate these activities may be DNA, RNA, peptides, proteins, or non-proteinaceous organic molecules. Compounds may modulate by increasing or attenuating the expression of DNA or RNA encoding NHL, or the function of the NHL-based protein. Compounds that modulate the expression of DNA or RNA encoding NHL or the biological function thereof may be detected by a variety of assays. The assay may be a simple “yes/no” assay to determine whether there is a change in expression or function. The assay may be made quantitative by comparing the expression or function of a test sample with the levels of expression or function in a standard sample. Kits containing NHL, antibodies to NHL, or modified NHL may be prepared by known methods for such uses.
The DNA molecules, RNA molecules, recombinant protein and antibodies of the present invention may be used to screen and measure levels of NHL. The recombinant proteins, DNA molecules, RNA molecules and antibodies lend themselves to the formulation of kits suitable for the detection and typing of NHL. Such a kit would comprise a compartmentalized carrier suitable to hold in close confinement at least one container. The carrier would further comprise reagents such as recombinant NHL or anti-NHL antibodies suitable for detecting NHL. The carrier may also contain a means for detection such as labeled antigen or enzyme substrates or the like.
The assays described above can be carried out with cells that have been transiently or stably transfected with NHL. The expression vector may be introduced into host cells via any one of a number of techniques including but not limited to transformation, transfection, protoplast fusion, and electroporation. Transfection is meant to include any method known in the art for introducing NHL into the test cells. For example, transfection includes calcium phosphate or calcium chloride mediated transfection, lipofection, infection with a retroviral construct containing NHL, and electroporation. The expression vector-containing cells are individually analyzed to determine whether they produce NHL protein. Identification of NHL expressing cells may be done by several means, including but not limited to immunological reactivity with anti-NHL antibodies, labeled ligand binding, the presence of host cell-associated NHL activity.
The specificity of binding of compounds showing affinity for NHL is shown by measuring the affinity of the compounds for recombinant cells expressing NHL. Expression of human NHL and screening for compounds that bind to NHL or that inhibit the binding of a known, radiolabeled ligand of NHL provides an effective method for the rapid selection of compounds with high affinity for NHL. Such ligands need not necessarily be radiolabeled but can also be nonisotopic compounds that can be used to displace bound radiolabeled compounds or that can be used as activators in functional assays. Compounds identified by the above method are likely to be agonists or antagonists of NHL and may be peptides, proteins, or non-proteinaceous organic molecules.
Accordingly, the present invention is directed to methods for screening for compounds which modulate the expression of DNA or RNA encoding a NHL protein as well as compounds which effect the function of the NHL protein. Methods for identifying agonists and antagonists of other receptors are well known in the art and can be adapted to identify agonists and antagonists of NHL. For example, Cascieri et al. (1992, Molec. Pharmacol. 41:1096-1099) describe a method for identifying substances that inhibit agonist binding to rat neurokinin receptors and thus are potential agonists or antagonists of neurokinin receptors. The method involves transfecting COS cells with expression vectors containing rat neurokinin receptors, allowing the transfected cells to grow for a time sufficient to allow the neurokinin receptors to be expressed, harvesting the transfected cells and resuspending the cells in assay buffer containing a known radioactively labeled agonist of the neurokinin receptors either in the presence or the absence of the substance, and then measuring the binding of the radioactively labeled known agonist of the neurokinin receptor to the neurokinin receptor. If the amount of binding of the known agonist is less in the presence of the substance than in the absence of the substance, then the substance is a potential agonist or antagonist of the neurokinin receptor. Where binding of the substance such as an agonist or antagonist to is measured, such binding can be measured by employing a labeled substance or agonist. The substance or agonist can be labeled in any convenient manner known to the art, e.g., radioactively, fluorescently, enzymatically.
Therefore, the present invention includes assays by which modulators of NHL are identified. As noted above, methods for identifying agonists and antagonists are known in the art and can be adapted to identify compounds which effect in vivo levels of NHL. Accordingly, the present invention includes a method for determining whether a substance is a potential modulator of mammalian NHL levels that comprises:

    
    
        (a) providing test cells by transfecting cells with an expression vector that directs the expression of NHL in the cells;
        (b) exposing the test cells to the substance;
        (c) measuring the amount of binding of the substance to NHL;
        (d) comparing the amount of binding of the substance to NHL in the test cells with the amount of binding of the substance to control cells that have not been transfected with NHL or a portion thereof; wherein if the amount of binding of the substance is greater in the test cells as compared to the control cells, the substance is capable of binding to NHL.
    
    


The conditions under which step (b) of the method is practiced are conditions that are typically used in the art for the study of protein-ligand interactions: e.g., physiological pH; salt conditions such as those represented by such commonly used buffers as PBS or in tissue culture media; a temperature of about 4° C. to about 55° C.
The assays described above can be carried out with cells that have been transiently or stably transfected with NHL. Transfection is meant to include any method known in the art for introducing NHL into the test cells. For example, transfection includes calcium phosphate or calcium chloride mediated transfection, lipofection, infection with a retroviral construct containing NHL, and electroporation.
Where binding of the substance or agonist to NHL is measured, such binding can be measured by employing a labeled substance or agonist. The substance or agonist can be labeled in any convenient manner known to the art, e.g., radioactively, fluorescently, enzymatically.
Therefore, the specificity of binding of compounds having affinity for NHL shown by measuring the affinity of the compounds for recombinant cells expressing the cloned receptor or for membranes from these cells. Expression of the cloned receptor and screening for compounds that bind to NHL or that inhibit the binding of a known, radiolabeled ligand of NHL to these cells provides an effective method for the rapid selection of compounds with high affinity for NHL. Such ligands need not necessarily be radiolabeled but can also be nonisotopic compounds that can be used to displace bound radiolabeled compounds or that can be used as activators in functional assays. It is also possible to construct assays wherein compounds are tested for an ability to modulate helicase activity in an in vitro- or in vivo-based assay. Compounds identified by the above method again are likely to be agonists or antagonists of NHL and may be peptides, proteins, or non-proteinaceous organic molecules. As noted elsewhere in this specification, compounds may modulate by increasing or attenuating the expression of DNA or RNA encoding NHL, or by acting as an agonist or antagonist of the NHL receptor protein. Again, these compounds that modulate the expression of DNA or RNA encoding NHL or the biological function thereof may be detected by a variety of assays. The assay may be a simple “yes/no” assay to determine whether there is a change in expression or function. The assay may be made quantitative by comparing the expression or function of a test sample with the levels of expression or function in a standard sample.
Expression of NHL DNA may also be performed using in vitro produced synthetic mRNA. Synthetic mRNA can be efficiently translated in various cell-free systems, including but not limited to wheat germ extracts and reticulocyte extracts, as well as efficiently translated in cell based systems, including but not limited to microinjection into frog oocytes, with microinjection into frog oocytes being preferred.
Following expression of NHL in a host cell, NHL protein may be recovered to provide NHL protein in active form. Several NHL protein purification procedures are available and suitable for use. Recombinant NHL protein may be purified from cell lysates and extracts by various combinations of, or individual application of salt fractionation, ion exchange chromatography, size exclusion chromatography, hydroxylapatite adsorption chromatography and hydrophobic interaction chromatography. In addition, recombinant NHL protein can be separated from other cellular proteins by use of an immunoaffinity column made with monoclonal or polyclonal antibodies specific for full-length NHL protein, or polypeptide fragments of NHL protein.
Polyclonal or monoclonal antibodies may be raised against NHL or a synthetic peptide (usually from about 9 to about 25 amino acids in length) from a portion of NHL disclosed in SEQ ID NO:2. Monospecific antibodies to NHL are purified from mammalian antisera containing antibodies reactive against NHL or are prepared as monoclonal antibodies reactive with NHL using the technique of Kohler and Milstein (1975, Nature 256: 495-497). Monospecific antibody as used herein is defined as a single antibody species or multiple antibody species with homogenous binding characteristics for NHL. Homogenous binding as used herein refers to the ability of the antibody species to bind to a specific antigen or epitope, such as those associated with NHL, as described above. Human NHL-specific antibodies are raised by immunizing animals such as mice, rats, guinea pigs, rabbits, goats, horses and the like, with an appropriate concentration of NHL protein or a synthetic peptide generated from a portion of NHL with or without an immune adjuvant.
Preimmune serum is collected prior to the first immunization. Each animal receives between about 0.1 mg and about 1000 mg of NHL protein associated with an acceptable immune adjuvant. Such acceptable adjuvants include, but are not limited to, Freund's complete, Freund's incomplete, alum-precipitate, water in oil emulsion containing Corynebacterium parvum and tRNA. The initial immunization consists of NHL protein or peptide fragment thereof in, preferably, Freund's complete adjuvant at multiple sites either subcutaneously (SC), intraperitoneally (IP) or both. Each animal is bled at regular intervals, preferably weekly, to determine antibody titer. The animals may or may not receive booster injections following the initial immunization. Those animals receiving booster injections are generally given an equal amount of NHL in Freund's incomplete adjuvant by the same route. Booster injections are given at about three week intervals until maximal titers are obtained. At about 7 days after each booster immunization or about weekly after a single immunization, the animals are bled, the serum collected, and aliquots are stored at about −20° C.
Monoclonal antibodies (mAb) reactive with NHL are prepared by immunizing inbred mice, preferably Balb/c, with NHL protein. The mice are immunized by the IP or SC route with about 1 mg to about 100 mg, preferably about 10 mg, of NHL protein in about 0.5 ml buffer or saline incorporated in an equal volume of an acceptable adjuvant, as discussed above. Freund's complete adjuvant is preferred. The mice receive an initial immunization on day 0 and are rested for about 3 to about 30 weeks. Immunized mice are given one or more booster immunizations of about 1 to about 100 mg of NHL in a buffer solution such as phosphate buffered saline by the intravenous (IV) route. Lymphocytes, from antibody positive mice, preferably splenic lymphocytes, are obtained by removing spleens from immunized mice by standard procedures known in the art. Hybridoma cells are produced by mixing the splenic lymphocytes with an appropriate fusion partner, preferably myeloma cells, under conditions which will allow the formation of stable hybridomas. Fusion partners may include, but are not limited to: mouse myelomas P3/NS1/Ag 4-1; MPC-11; S-194 and Sp 2/0, with Sp 2/0 being preferred. The antibody producing cells and myeloma cells are fused in polyethylene glycol, about 1000 mol. wt., at concentrations from about 30% to about 50%. Fused hybridoma cells are selected by growth in hypoxanthine, thymidine and aminopterin supplemented Dulbecco's Modified Eagles Medium (DMEM) by procedures known in the art. Supernatant fluids are collected form growth positive wells on about days 14, 18, and 21 and are screened for antibody production by an immunoassay such as solid phase immunoradioassay (SPIRA) using NHL as the antigen. The culture fluids are also tested in the Ouchterlony precipitation assay to determine the isotype of the mAb. Hybridoma cells from antibody positive wells are cloned by a technique such as the soft agar technique of MacPherson, 1973, Soft Agar Techniques, in Tissue Culture Methods and Applications, Kruse and Paterson, Eds., Academic Press.
Monoclonal antibodies are produced in vivo by injection of pristine primed Balb/c mice, approximately 0.5 ml per mouse, with about 2×106 to about 6×106 hybridoma cells about 4 days after priming. Ascites fluid is collected at approximately 8-12 days after cell transfer and the monoclonal antibodies are purified by techniques known in the art.
In vitro production of anti-NHL mAb is carried out by growing the hybridoma in DMEM containing about 2% fetal calf serum to obtain sufficient quantities of the specific mAb. The mAb are purified by techniques known in the art.
Antibody titers of ascites or hybridoma culture fluids are determined by various serological or immunological assays which include, but are not limited to, precipitation, passive agglutination, enzyme-linked immunosorbent antibody (ELISA) technique and radioimmunoassay (RIA) techniques. Similar assays are used to detect the presence of NHL in body fluids or tissue and cell extracts.
It is readily apparent to those skilled in the art that the above described methods for producing monospecific antibodies may be utilized to produce antibodies specific for NHL peptide fragments, or a respective full-length NHL.
NHL antibody affinity columns are made, for example, by adding the antibodies to Affigel-10 (Biorad), a gel support which is pre-activated with N-hydroxysuccinimide esters such that the antibodies form covalent linkages with the agarose gel bead support. The antibodies are then coupled to the gel via amide bonds with the spacer arm. The remaining activated esters are then quenched with 1M ethanolamine HCl (pH 8). The column is washed with water followed by 0.23 M glycine HCl (pH 2.6) to remove any non-conjugated antibody or extraneous protein. The column is then equilibrated in phosphate buffered saline (pH 7.3) and the cell culture supernatants or cell extracts containing full-length NHL or NHL protein fragments are slowly passed through the column. The column is then washed with phosphate buffered saline until the optical density (A280) falls to background, then the protein is eluted with 0.23 M glycine-HCl (pH 2.6). The purified NHL protein is then dialyzed against phosphate buffered saline.
Pharmaceutically useful compositions comprising modulators of NHL may be formulated according to known methods such as by the admixture of a pharmaceutically acceptable carrier. Examples of such carriers and methods of formulation may be found in Remington's Pharmaceutical Sciences. To form a pharmaceutically acceptable composition suitable for effective administration, such compositions will contain an effective amount of the protein, DNA, RNA, modified NHL, or either NHL agonists or antagonists including tyrosine kinase activators or inhibitors.
Therapeutic or diagnostic compositions of the invention are administered to an individual in amounts sufficient to treat or diagnose disorders. The effective amount may vary according to a variety of factors such as the individual's condition, weight, sex and age. Other factors include the mode of administration.
The pharmaceutical compositions may be provided to the individual by a variety of routes such as subcutaneous, topical, oral and intramuscular.
The term “chemical derivative” describes a molecule that contains additional chemical moieties which are not normally a part of the base molecule. Such moieties may improve the solubility, half-life, absorption, etc. of the base molecule. Alternatively the moieties may attenuate undesirable side effects of the base molecule or decrease the toxicity of the base molecule. Examples of such moieties are described in a variety of texts, such as Remington's Pharmaceutical Sciences.
Compounds identified according to the methods disclosed herein may be used alone at appropriate dosages. Alternatively, co-administration or sequential administration of other agents may be desirable.
The present invention also has the objective of providing suitable topical, oral, systemic and parenteral pharmaceutical formulations for use in the novel methods of treatment of the present invention. The compositions containing compounds identified according to this invention as the active ingredient can be administered in a wide variety of therapeutic dosage forms in conventional vehicles for administration. For example, the compounds can be administered in such oral dosage forms as tablets, capsules (each including timed release and sustained release formulations), pills, powders, granules, elixirs, tinctures, solutions, suspensions, syrups and emulsions, or by injection. Likewise, they may also be administered in intravenous (both bolus and infusion), intraperitoneal, subcutaneous, topical with or without occlusion, or intramuscular form, all using forms well known to those of ordinary skill in the pharmaceutical arts.
Advantageously, compounds of the present invention may be administered in a single daily dose, or the total daily dosage may be administered in divided doses of two, three or four times daily. Furthermore, compounds for the present invention can be administered in intranasal form via topical use of suitable intranasal vehicles, or via transdermal routes, using those forms of transdermal skin patches well known to those of ordinary skill in that art. To be administered in the form of a transdermal delivery system, the dosage administration will, of course, be continuous rather than intermittent throughout the dosage regimen.
For combination treatment with more than one active agent, where the active agents are in separate dosage formulations, the active agents can be administered concurrently, or they each can be administered at separately staggered times.
The dosage regimen utilizing the compounds of the present invention is selected in accordance with a variety of factors including type, species, age, weight, sex and medical condition of the patient; the severity of the condition to be treated; the route of administration; the renal, hepatic and cardiovascular function of the patient; and the particular compound thereof employed. A physician or veterinarian of ordinary skill can readily determine and prescribe the effective amount of the drug required to prevent, counter or arrest the progress of the condition. Optimal precision in achieving concentrations of drug within the range that yields efficacy without toxicity requires a regimen based on the kinetics of the drug's availability to target sites. This involves a consideration of the distribution, equilibrium, and elimination of a drug.
The present invention also relates to a non-human transgenic animal which is useful for studying the ability of a variety of compounds to act as modulators of NHL, or any alternative functional NHL in vivo by providing cells for culture, in vitro. In reference to the transgenic animals of this invention, reference is made to transgenes and genes. As used herein, a transgene is a genetic construct including a gene. The transgene is integrated into one or more chromosomes in the cells in an animal by methods known in the art. Once integrated, the transgene is carried in at least one place in the chromosomes of a transgenic animal. Of course, a gene is a nucleotide sequence that encodes a protein, such as one or a combination of the cDNA clones described herein. The gene and/or transgene may also include genetic regulatory elements and/or structural elements known in the art. A type of target cell for transgene introduction is the embryonic stem cell (ES). ES cells can be obtained from pre-implantation embryos cultured in vitro and fused with embryos (Evans et al., 1981, Nature 292:154-156; Bradley et al., 1984, Nature 309:255-258; Gossler et al., 1986, Proc. Natl. Acad. Sci. USA 83:9065-9069; and Robertson et al., 1986 Nature 322:445-448). Transgenes can be efficiently introduced into the ES cells by a variety of standard techniques such as DNA transfection, microinjection, or by retrovirus-mediated transduction. The resultant transformed ES cells can thereafter be combined with blastocysts from a non-human animal. The introduced ES cells thereafter colonize the embryo and contribute to the germ line of the resulting chimeric animal (Jaenisch, 1988, Science 240: 1468-1474). It will also be within the purview of the skilled artisan to produce transgenic or knock-out invertebrate animals (e.g., C. elegans) which express the NHL transgene in a wild type background as well in C. elegans mutants knocked out for one or both of the NHL subunits. These organisms will be helpful in further determining the dominant negative effect of NHL as well as selecting from compounds which modulate this effect.
The present invention also relates to a non-human transgenic animal which is heterozygous for a functional NHL gene native to that animal. As used herein, functional is used to describe a gene or protein that, when present in a cell or in vitro system, performs normally as if in a native or unaltered condition or environment. The animal of this aspect of the invention is useful for the study of the retinal specific expression or activity of NHL in an animal having only one functional copy of the gene. The animal is also useful for studying the ability of a variety of compounds to act as modulators of NHL activity or expression in vivo or, by providing cells for culture, in vitro. It is reiterated that as used herein, a modulator is a compound that causes a change in the expression or activity of NHL, or causes a change in the effect of the interaction of NHL with its ligand(s), or other protein(s). In an embodiment of this aspect, the animal is used in a method for the preparation of a further animal which lacks a functional native NHL gene. In another embodiment, the animal of this aspect is used in a method to prepare an animal which expresses a non-native NHL gene in the absence of the expression of a native NHL gene. In particular embodiments the non-human animal is a mouse. In further embodiments the non-native NHL is a wild-type human NHL which is disclosed herein, or any other biologically equivalent form of human NHL gene as also disclosed herein.
In reference to the transgenic animals of this invention, reference is made to transgenes and genes. As used herein, a transgene is a genetic construct including a gene. The transgene is integrated into one or more chromosomes in the cells in an animal by methods known in the art. Once integrated, the transgene is carried in at least one place in the chromosomes of a transgenic animal. Of course, a gene is a nucleotide sequence that encodes a protein, such as human or mouse NHL. The gene and/or transgene may also include genetic regulatory elements and/or structural elements known in the art.
Another aspect of the invention is a non-human animal embryo deficient for native NHL expression. This embryo is useful in studying the effects of the lack of NHL on the developing animal. In particular embodiments the animal is a mouse. The animal embryo is also useful as a source of cells lacking a functional native NHL gene. The cells are useful in in vitro culture studies in the absence of NHL.
An aspect of this invention is a method to obtain an animal in which the cells lack a functional gene NHL native to the animal. The method includes providing a gene for an altered form of the NHL gene native to the animal in the form of a transgene and targeting the transgene into a chromosome of the animal at the place of the native NHL gene. The transgene can be introduced into the embryonic stem cells by a variety of methods known in the art, including electroporation, microinjection, and lipofection. Cells carrying the transgene can then be injected into blastocysts which are then implanted into pseudopregnant animals. In alternate embodiments, the transgene-targeted embryonic stem cells can be coincubated with fertilized eggs or morulae followed by implantation into females. After gestation, the animals obtained are chimeric founder transgenic animals. The founder animals can be used in further embodiments to cross with wild-type animals to produce F1 animals heterozygous for the altered NHL gene. In further embodiments, these heterozygous animals can be interbred to obtain the non-viable transgenic embryos whose somatic and germ cells are homozygous for the altered NHL gene and thereby lack a functional NHL gene. In other embodiments, the heterozygous animals can be used to produce cells lines. In preferred embodiments, the animals are mice.
A further aspect of the present invention is a transgenic non-human animal which expresses a non-native NHL on a native NHL null background. In particular embodiments, the null background is generated by producing an animal with an altered native NHL gene that is non-functional, i.e. a knockout. The animal can be heterozygous (i.e., having a different allelic representation of a gene on each of a pair of chromosomes of a diploid genome) or homozygous (i.e., having the same representation of a gene on each of a pair of chromosomes of a diploid genome) for the altered NHL gene and can be hemizygous (i.e., having a gene represented on only one of a pair of chromosomes of a diploid genome) or homozygous for the non-native NHL gene. In preferred embodiments, the animal is a mouse. In particular embodiments the non-native NHL gene can be a wild-type or mutant allele including those mutant alleles associated with a disease. In further embodiments, the non-native NHL is a human NHL. In a further embodiment the non-native NHL gene is operably linked to a promoter. As used herein, operably linked is used to denote a functional connection between two elements whose orientation relevant to one another can vary. In this particular case, it is understood in the art that a promoter can be operably linked to the coding sequence of a gene to direct the expression of the coding sequence while placed at various distances from the coding sequence in a genetic construct.
An aspect of this invention is a method of producing transgenic animals having a transgene including a non-native NHL gene on a native NHL null background. The method includes providing transgenic animals of this invention whose cells are heterozygous for a native gene encoding a functional NHL protein and an altered native NHL gene. These animals are crossed with transgenic animals of this invention that are hemizygous for a transgene including a non-native NHL gene to obtain animals that are both heterozygous for an altered native NHL gene and hemizygous for a non-native NHL gene. The latter animals are interbred to obtain animals that are homozygous or hemizygous for the non-native NHL and are homozygous for the altered native NHL gene. In particular embodiments, cell lines are produced from any of the animals produced in the steps of the method.
The transgenic animals and cells of this invention are useful in the determination of the in vivo function of a non-native NHL in the central nervous system and in other tissues of an animal. The animals are also useful in studying the tissue and temporal specific expression patterns of a non-native NHL throughout the animals. The animals are also useful in determining the ability for various forms of wild-type and mutant alleles of a non-native NHL to rescue the native NHL null deficiency. The animals are also useful for identifying and studying the ability of a variety of compounds to act as modulators of the expression or activity of a non-native NHL in vivo, or by providing cells for culture, for in vitro studies.
As used herein, a “targeted gene” or “Knockout” (KO) is a DNA sequence introduced into the germline of a non-human animal by way of human intervention, including but not limited to, the methods described herein. The targeted genes of the invention include nucleic acid sequences which are designed to specifically alter cognate endogenous alleles. An altered NHL gene should not fully encode the same NHL as native to the host animal, and its expression product can be altered to aminor or great degree, or absent altogether. In cases where it is useful to express a non-native NHL gene in a transgenic animal in the absence of a native NHL gene we prefer that the altered NHL gene induce a null lethal knockout phenotype in the animal. However a more modestly modified NHL gene can also be useful and is within the scope of the present invention.
A type of target cell for transgene introduction is the embryonic stem cell (ES). ES cells can be obtained from pre-implantation embryos cultured in vitro and fused with embryos (Evans et al., 1981, Nature 292:154-156; Bradley et al., 1984, Nature 309:255-258; Gossler et al., 1986, Proc. Natl. Acad. Sci. USA 83:9065-9069; and Robertson et al., 1986 Nature 322:445-448). Transgenes can be efficiently introduced into the ES cells by a variety of standard techniques such as DNA transfection, microinjection, or by retrovirus-mediated transduction. The resultant transformed ES cells can thereafter be combined with blastocysts from a non-human animal. The introduced ES cells thereafter colonize the embryo and contribute to the germ line of the resulting chimeric animal (Jaenisch, 1988, Science 240: 1468-1474).
The methods for evaluating the targeted recombination events as well as the resulting knockout mice are readily available and known in the art. Such methods include, but are not limited to DNA (Southern) hybridization to detect the targeted allele, polymerase chain reaction (PCR), polyacrylamide gel electrophoresis (PAGE) and Western blots to detect DNA, RNA and protein.
The following examples are provided to illustrate the present invention without, however, limiting the same hereto.
EXAMPLE 1
Characterization of DNA Molecules Encoding NHL
M68/DcR3 identification—The human osteoprotegerin (OPG) sequence (Acc. #U94332), which is a member of the TNFR-related family, was used to searched Genbank using the programs TBLASTN and TFASTX3 to identify novel gene family members. Two EST sequences (GenBank Acc. #AA155701 and AA025672) were identified that showed sequence similarities to the cysteine repeats of the OPG sequence. These EST sequences were then used to identify additional EST sequences, which formed a single EST cluster (GenBank Acc. #s aa577603, aa603704, aa613366, aa158406, w67560, aa325843, aa155646, aa025673, aa514270, m91489). Two clones were further characterized, which were derived from colon tumor and germ cell tumor libraries (Research Genetics, Inc). DNA sequence analysis revealed two alternatively spliced forms of the 5′-end UTR of M68/DcR3. The M68/DcR3 open reading frame was confirmed by sequence analysis of clones obtained by PCR cloning from a normal human cDNA library (Clontech).
M68/DcR3 BAC identification and sequencing—To further delineate the gene structure of M68/DcR3, genomic DNA was obtained using a human “Down to the Well”TM genomic bacterial artificial chromosome (BAC) library (Genome Systems, Inc.) according to the manufacturer's protocol. Two sets of PCR primers, C68.36F: 5′-CACAGGTTCAGCATGTTTGTGCGTC-3′ (SEQ ID NO:4) and C68.275R: 5′-CACAGTCCCTGCTGGCCTCTGTCTA-3′ (SEQ ID NO:5), and E68.715F: 5′-CAGGACATCTCCATCAAGAGGCTGC-3′ (SEQ ID NO:6) and E68.972R: 5′-AATAAGAGGGGGCCAGGATCAGTGC-3′ (SEQ ID NO:7), were used to carry out PCR reactions to identify positive wells that contained the full-length M68/DcR3 gene. The PCR conditions used were 94° C. for 9 min, 35 cycles of (94° C., 30 sec., 68° C. 3 min.) followed by 72° C. for 10 min. Two positive BAC clones were identified and characterized by restriction digestion and BAC-end sequence analyses, of which hbm168 was selected for shotgun sequencing.
A shot-gun library for BAC hbm168 was constructed using a conventional strategy. Briefly, two 150-ml bacterial cultures were combined and purified using a modified protocol of the plasmid-Maxi kit (QIAGEN) followed by CsCl gradient purification. After butanol extraction and isopropanol precipitation, BAC DNA was nebulizied at 10 psi for 60 seconds to generate randomly sheared fragments. Following ethanol precipitation, the fragments were end-repaired using T4 polymerase (Promega) and BstXI adaptors (Invitrogen) were ligated overnight. Removal of excess, unligated adaptors and size selection was performed using a cDNA sizing column (Life Technologies, Inc.) to generate genomic fragments in the size range of 1500 to 3000 bp. Adaptor ligated fragments were cloned into a modified pBlueScript SK+ vector (Stratagene) and transformed in XL2-Blue ultracompentent cells (Stratagene). Approximately 1000 clones were isolated, plasmids were purified using the Turbo miniprep kits (QIAGEN), and both plasmid ends were sequenced with the BigDye terminator kits (Perkin-Elmer). Sequence data were assembled using Phred/Phrap/Consed where single-stranded and gap regions were closed using a directed sequencing strategy.
NHL identification and sequencing—The genomic clone for the NHL gene was obtained and sequenced. The transcript was identified through exon prediction using GRAIL2 and sequence alignment to a contiguous 4.5 kilobase region of chromosome 4 (88% sequence identity). The complete exon structure of NHL was subsequently confirmed by RT-PCR analysis. The exon structure was confirmed by RT-PCR using polyA RNA from a human colorectal adenocarcinoma cell line, SW480 (Clontech). Primers were designed based on the genomic sequence that were predicted to be exons. RT-PCR reaction were carried out with SW480 polyA RNA using standard conditions with TaqGold Enzyme at 94° C. for 12 min, 35 cycles of (94° C., 30 sec., 60C, 30 sec., and 68° C. 2-6 min.) followed by 68° C. for 7 min. Most sequence confirmation was accomplished by RT-PCR, although first junction between exon 1 and 2 was confirmed by 5′RACE and junctions between exon 26-29 were by RCCA. The primers used were as follows:












Junction of Exons
Confirmed by Primers







H01/H02
hdkw (5′RACE)



 


H02/H03
hdiy, hdiz


 


H03-H09
hdid, hdie, hdja, hdjb


 


H09-H13
hdja, hdie


 


H13-H18
hdje, hdjf


 


H18-H23
hdjg, hdjh


 


H23-H26
hdji, hdjj


 


H26-H29
hdkv, r543(RCCA)


 


H29-H31
hdij, hdmu, hdnd, hdne


 


H31/H32
hdij, hdmu


 


H32/H34
hdip, hdil, hdmv, hdik, hdli


 


H34/H35
hdng, hdnh


 









HDID - 5′-GTGAATGGCATCCTGGAGAG-3′;
(SEQ ID NO:8)



 


HDIE - 5′-GTCTCCAGGCAGCTCAACAG-3′;
(SEQ ID NO:9)


 


HDIJ - 5′-ACCCTGTCCCTCCTGTCTGA-3′;
(SEQ ID NO:10)


 


HDIY - 5′-AGACCCTAAGATGTTCGGAG-3′;
(SEQ ID NO:11)


 


HDIZ - 5′-GATGACCTGTGTGAGTTGCG-3′;
(SEQ ID NO:12)


 


HDJA - 5′-CGCAACTCACACAGGTCATC-3′;
(SEQ ID NO:13)


 


HDJB - 5′-GGAGTCAGGTCAAAGGATGC-3′;
(SEQ ID NO:14)


 


HDJC - 5′-GCATCCTTTGACCTGACTCC-3′;
(SEQ ID NO:15)


 


HDJD - 5′-GGTCTGAAACGTGATCTGGG-3′;
(SEQ ID NO:16)


 


HDJE - 5′-CCCAGATCACGTTTCAGACC-3′;
(SEQ ID NO:17)


 


HDJF - 5′-CGATGATGTGTGGGTTCTCC-3′;
(SEQ ID NO:18)


 


HDJG - 5′-GGAGAACCGACACATCATCG-3′;
(SEQ ID NO:19)


 


HDJH - 5′-CGTGTCTGAGAAGTCCAGCC-3′;
(SEQ ID NO:20)


 


HDJI - 5′-GGCTGGACTTCTCAGACACG-3′;
(SEQ ID NO:21)


 


HDJJ - 5′-ACAGCATCTTCTCCACGCAC-3′;
(SEQ ID NO:22)


 


HFMU - 5′-AGTCCTCTGGCTTTGCAGTG-3′;
(SEQ ID NO:23)


 


HDKV - 5′-TGTGCGTGGAGAAGATGCTG-3′;
(SEQ ID NO:24)


 


HDKW - 5′-GGCTGGAAAGGGAAGTCTAC-3′;
(SEQ ID NO:25)


 


HDND - 5′-TGGTTCAGGTGCTCTTGGGG-3′;
(SEQ ID NO:26)


 


HDNE - 5′-CGTGAAGCAGGAGTTGAGCC-3′;
(SEQ ID NO:27)


 


HDIK - 5′-ATCTTGCTCTGGGTCTTCCC-3′;
(SEQ ID NO:28)


 


HDIL - 5′-CACTGCAAAGCCAGAGGACT-3′;
(SEQ ID NO:29)


 


HDIP - 5′-ATAAGCAAGACGACGACCTC-3′;
(SEQ ID NO:30)


 


HDLI - 5′-CTATTCTGTTGGGTGGGTTC-3′;
(SEQ ID NO:31)


 


HDMV - 5′-CGTGCCTCCTGTGCTTACCC-3′;
(SEQ ID NO:32)


 


HDNG - 5′-CAGACCCCAAGGTAGCTCAG-3′;
(SEQ ID NO:33)


 


HDNH - 5′-GGAAGACCCAGAGCAAGATC-3′.
(SEQ ID NO:34)









Amplified product were subject to direct sequencing after purification from an agarose gel or cloned into a TOPO PCR cloning vector (Invitrogen) for sequencing. Multiple sequence alignment of NHL to known helicases showed that NHL contains all the seven critical helicase domains. BLAST analysis of the predicted 1,219 amino acid sequence (see FIG. 2, SEQ ID NO:2) reveal an approximately 26% sequence identity and 48% sequence similarity to the RAD3/ERCC2 gene family of DNA helicases (see FIG. 3). Review of this sequence data shows that two partial human cDNA clones (Acc. No. a1080127 and ab029011) are deposited. No. a1080127 covers exon 25-35 while ab029011 covers exons 9-35. Ab029011 starts at amino acid 240 of the full length human NHL protein disclosed herein, but also differs at exon 35 and appears to be a fusion transcript with M68. This cDNA was isolated from brain tissue, which has been known to express rare transcripts.

EXAMPLE 2
Northern Analysis of Human NHL Expression
Messenger RNA (mRNA) obtained from human brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung, and peripheral blood leukocytes. Two μg of polyA+ RNA were run on each lane a denaturing formaldehyde 1% agarose gel, and transferred to a charged-modified nylon membrane. The probe was made using a 733 bp fragment derived from 1174-1907 nt of the NHL cDNA. This fragment was labeled via the 32P dCTP random priming method (Ambion). Hybridization was carried in ExpressHyb (Clontech) according to the manufacturer's protocol except for the final wash, which was at 55° C. Membranes were exposed to X-ray film with intensifying screen at −80° C. overnight. The Northern data is presented in FIG. 4. Note hybridization of the NHL probe to an approximately 4.4 kb transcript. The 7.5 kb transcript may suggest an alternative splicing of the NHL RNA.
EXAMPLE 3
Chromosomal Localization
To map the position of M68/NHL in the human genome, primers C68.36F and C68.275R, were used to carry out PCR reactions to 93 clones of the MIT GeneBridge 4 panel (Research Genetics) and results were submitted to MIT for analysis. M68/DcR3 was mapped to the extreme telomere of chromosome 20, at 20q13.3, 28cR from D20S173 with a lod score of 13. An analogous procedure was also carried out with the 83 clones of the Stanford G3 radiation hybrid panel, with PCR results submitted to the Stanford Genome Center for analysis. Analysis using another pair of PCR primers specific to NHL yielded the same result. For fluorescence in situ (FISH) analysis, the normal human male fibroblast cell line, L136 (Coriell Cell Repository, Camden, N.J.) was arrested in mitosis with colcemid (10 μg/ml). A human chromosome 20 α-satellite probe (Vysis, Downers Grove, Ill.) was directly labeled with Spectrum Orange dUTP and was used to identify chromosome 20. The M68 BAC clone was directly labeled with SpectrumGreen dUTP by nick translation (Vysis). Slides were counterstained with DAPI stain and viewed under an Olympus microscope with narrow blue and DAPI/TRITC filters. Fifty metaphase cells were scored to verify that the M68 probe was located on the same chromosome as the Human Chromosome 20 probe. Radiation hybrid chromosomal mapping reconfirms that it is linked to M68 locus, at 20q13.3.

## Claims

1. A substantially purified human helicase protein which comprises the amino acid sequence as set forth in SEQ ID NO:2.

2. A substantially purified human helicase protein which consists of the amino acid sequence as set forth in SEQ ID NO:2.