CA2395378A1 - Dna molecules encoding human nhl, a dna helicase - Google Patents

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.

Description

TITLE OF THE INVENTION
DNA MOLECULES ENCODING HUMAN NHL, A DNA HELICASE
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims the benefit, under 35 U.S.C. ~ 119(e), of U.S.
provisional application 60/169,970 filed December 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, SCUP, 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 C1, daunorubicin and nogalamycin (Tuteja, et al., 1997, Biochem.
Biophys. Res. Comm. 236(3):636-640), and a prostate cancer drug, CI-958 (Lun, et a1.,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.
2o 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 Figure lA-B and SEQ ID NO:1.
The present invention also relates to biologically active fragments or mutants 3o 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 Figure 2 and as set forth as SEQ ID N0:2. 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 Figure 2 and set l0 forth as SEQ )D N0:2.
A preferred aspect of this portion of the present invention is a NHL protein which consists of the amino acid sequence disclosed in Figure 2 and set forth as SEQ
ID N0:2.
Another preferred aspect of the present invention relates to a substantially 15 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: I 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.
20 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
N0:2, 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 25 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 Figure 2 and is set forth as SEQ 117 N0:2, a respective amino acid sequence which encodes human NHL.
Characterization of one or more of these DNA helicase-like proteins allows for 30 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 1o 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 15 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 >D NO:1, a 115 kb genomic fragment set forth herein as SEQ ~
20 N0:3. As especially preferred aspect of this portion of the invention is the region of the genomic fragment of SEQ m N0:3 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, SCUP
and ARP. As discussed herein, it has been shown that this region of chromosome 25 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 3o 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 Figure 2 and SEQ ID
N0:2. 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 1o 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.
15 It is an object of the present invention to provide a substantially purified form of human NHL, as set forth in Figure 2 and SEQ ID N0:2.
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 2o 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 25 forth in SEQ ID N0:2, 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 30 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°0, 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 1o 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 15 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 2o 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 25 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 3o 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 occurnng NHL
disclosed herein comprises the amino acid sequence shown as SEQ ID N0:2 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).
2o As used herein, the term "mammalian" will refer to any mammal, including a human being.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure lA-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.
Figure 2 shows the amino acid sequence of human NHL as set forth in SEQ ID
N0:2.
Figure 3 shows the alignment of amino acid sequences of human NHL to 3o ERCC2/RAD3 gene family members. Rep D (Dictyosteliem discoideum); RAD 3 (S. cerevisiae); RAD15 (S. pombe) and XP GroupD (Homo sapien).
Figure 4 shows Northern analysis of NHL expression in multi-human tissues.
Figure SA-B show the genomic structure of the NHL gene (Figure 5A) and the entire 115 kb genomic region (Figure 5B) containing the NHL, M68/DcR3, SCUP

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 1o 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 2o 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
3o helicases (Naumovski et al., 1985 Mol. Cell Biol. 5:17-26; Reynolds et al., 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.
_g_ 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 Figure and SEQ
lA-B 1D NO:I, which is as follows:

AGTCAGCCCTGCTGCCAGCCAGTGCCGGGTGCTGGGGACTCAGGGAGGCCCGCCGGGACC

ACTGCGGGACAGTGAGCCGAGCAGAAGCTGGAACGCAGGAGAGGAAGGAGAGGGGGCGGT

CAGGGCTCTCAGGAGCCGGGTCCTGGGCAAGGCGCAGCCGTTTTCAAATTTTCAGGAAAG

CGGTCGGCTCACACTCGAGCAGTAAAAAGATGCCTCTGGGGAGGAGGCCCGTGCAGCTCT

CCGGGCAATGGTGGTGGCTCGGCCTAGAGAGGCGGTAGTGGAACGCAGACCCTGGTGGGG

GAATGACATCAAGGGAGGAGACGGGCGGGACCCCAGATTTCTGCCTGTGGGCGATGGAAG

TGAGGTTCACTGGCCAGCGGAGCCGGACACAGAACGCGCAAAACGCCGTGTAGGCCTGGA

GGAGCCGAAGAGCAGGCGGACCCCCTCCGCGGGGGAACAGTTTCCGCCGGGAGCACAAAG

CAACGGACCGGAAGTGGGGGGCGGAAGTGCAGTGGGCTCAGCGCCGACTGCGCGCCTCTG

CCCGCGAAAACTCTGAGCTGGCTGACAGCTGGGGACGGGTGGCGGCCCTCGACTGGAGTC

GGTTGAGTTCCTGAGGGACCCCGGTTCTGGAAGGTTCGCCGCGGAGACAAGTGAGCAGTC

TGTGCCATAGGGATTCTCGAAGAGAACAGCGTTGTGTCCCAGTGCACATGCTCGCATCGC

TTACCAGGAGTGCCCGAGACCCTAAGATGTTCGGAGTGGTTTTTTCGCACAGACCCGAAT

AGCCTGCCCCTCAGCCACGCTCTGTGCCCTTCTGAGAACAGGCTGATATGCCCAAGATAG

TCCTGAATGGTGTGACCGTAGACTTCCCTTTCCAGCCCTACAAATGCCAACAGGAGTACA

TGACCAAGGTCCTGGAATGTCTGCAGCAGAAGGTGAATGGCATCCTGGAGAGCCCTACGG

GTACAGGGAAGACGCTGTGCCTGCTGTGCACCACGCTGGCCTGGCGAGAACACCTCCGAG

ACGGCATCTCTGCCCGCAAGATTGCCGAGAGGGCGCAAGGAGAGCTTTTCCCGGATCGGG

CCTTGTCATCCTGGGGCAACGCTGCTGCTGCTGCTGGAGACCCCATAGCTTGCTACACGG

ACATCCCAAAGATTATTTACGCCTCCAGGACCCACTCGCAACTCACACAGGTCATCAACG

AGCTTCGGAACACCTCCTACCGGCCTAAGGTGTGTGTGCTGGGCTCCCGGGAGCAGCTGT

GCATCCATCCTGAGGTGAAGAAACAAGAGAGTAACCATCTACAGATCCACTTGTGCCGTA

AGAAGGTGGCAAGTCGCTCCTGTCATTTCTACAACAACGTAGAAGAAAAAAGCCTGGAGC

AGGAGCTGGCCAGCCCCATCCTGGACATTGAGGACTTGGTCAAGAGCGGAAGCAAGCACA

GGGTGTGCCCTTACTACCTGTCCCGGAACCTGAAGCAGCAAGCCGACATCATATTCATGC

CGTACAATTACTTGTTGGATGCCAAGAGCCGCAGAGCACACAACATTGACCTGAAGGGGA

CAGTCGTGATCTTTGACGAAGCTCACAACGTGGAGAAGATGTGTGAAGAATCGGCATCCT

TTGACCTGACTCCCCATGACCTGGCTTCAGGACTGGACGTCATAGACCAGGTGCTGGAGG

AGCAGACCAAGGCAGCGCAGCAGGGTGAGCCCCACCCGGAGTTCAGCGCGGACTCCCCCA

GCCCAGGGCTGAACATGGAGCTGGAAGACATTGCAAAGCTGAAGATGATCCTGCTGCGCC

TGGAGGGGGCCATCGATGCTGTTGAGCTGCCTGGAGACGACAGCGGTGTCACCAAGCCAG

GGAGCTACATCTTTGAGCTGTTTGCTGAAGCCCAGATCACGTTTCAGACCAAGGGCTGCA

TCCTGGACTCGCTGGACCAGATCATCCAGCACCTGGCAGGACGTGCTGGAGTGTTCACCA

ACACGGCCGGACTGCAGAAGCTGGCGGACATTATCCAGATTGTGTTCAGTGTGGACCCCT

CCGAGGGCAGCCCTGGTTCCCCAGCAGGGCTGGGGGCCTTACAGTCCTATAAGGTGCACA

S TCCATCCTGATGCTGGTCACCGGAGGACGGCTCAGCGGTCTGATGCCTGGAGCACCACTG

CAGCCAGAAAGCGAGGGAAGGTGCTGAGCTACTGGTGCTTCAGTCCCGGCCACAGCATGC

ACGAGCTGGTCCGCCAGGGCGTCCGCTCCCTCATCCTTACCAGCGGCACGCTGGCCCCGG

TGTCCTCCTTTGCTCTGGAGATGCAGATCCCTTTCCCAGTCTGCCTGGAGAACCCACACA

TCATCGACAAGCACCAGATCTGGGTGGGGGTCGTCCCCAGAGGCCCCGATGGAGCCCAGT

TGAGCTCCGCGTTTGACAGACGGTTTTCCGAGGAGTGCTTATCCTCCCTGGGGAAGGCTC

TGGGCAACATCGCCCGCGTGGTGCCCTATGGGCTCCTGATCTTCTTCCCTTCCTATCCTG

TCATGGAGAAGAGCCTGGAGTTCTGGCGGGCCCGCGACTTGGCCAGGAAGATGGAGGCGC

TGAAGCCGCTGTTTGTGGAGCCCAGGAGCAAAGGCAGCTTCTCCGAGACCATCAGTGCTT

ACTATGCAAGGGTTGCCGCCCCTGGGTCCACCGGCGCCACCTTCCTGGCGGTCTGCCGGG

GCCTCCCGTACCCCCCACGCATGGACCCCCGGGTTGTCCTCAAGATGCAGTTCCTGGATG

AGATGAAGGGCCAGGGTGGGGCTGGGGGCCAGTTCCTCTCTGGGCAGGAGTGGTACCGGC

AGCAGGCGTCCAGGGCTGTGAACCAGGCCATCGGGCGAGTGATCCGGCACCGCCAGGACT

ACGGAGCTGTCTTCCTCTGTGACCACAGGTTCGCCTTTGCCGACGCAAGAGCCCAACTGC

CCTCCTGGGTGCGTCCCCACGTCAGGGTGTATGACAACTTTGGCCATGTCATCCGAGACG

TGGCCCAGTTCTTCCGTGTTGCCGAGCGAACTATGCCAGCGCCGGCCCCCCGGGCTACAG

CACCCAGTGTGCGTGGAGAAGATGCTGTCAGCGAGGCCAAGTCGCCTGGCCCCTTCTTCT

CCACCAGGAAAGCTAAGAGTCTGGACCTGCATGTCCCCAGCCTGAAGCAGAGGTCCTCAG

GGTCACCAGCTGCCGGGGACCCCGAGAGTAGCCTGTGTGTGGAGTATGAGCAGGAGCCAG

CGGGGAGCCCTGGCGAGGAGCAGGCCCACAGCTGCTCCACCCTGTCCCTCCTGTCTGAGA

AGAGGCCGGCAGAAGAACCGCGAGGAGGGAGGAAGAAGATCCGGCTGGTCAGCCACCCGG

AGGAGCCCGTGGCTGGTGCACAGACGGACAGGGCCAAGCTCTTCATGGTGGCCGTGAAGC

AGGAGTTGAGCCAAGCCAACTTTGCCACCTTCACCCAGGCCCTGCAGGACTACAAGGGTT

CCGATGACTTCGCCGCCCTGGCCGCCTGTCTCGGCCCCCTCTTTGCTGAGGACCCCAAGA

AGCACAACCTGCTCCAAGGCTTCTACCAGTTTGTGCGGCCCCACCATAAGCAGCAGTTTG

AGGAGGTCTGTATCCAGCTGACAGGACGAGGCTGTGGCTATCGGCCTGAGCACAGCATTC

CCCGAAGGCAGCGGGCACAGCCGGTCCTGGACCCCACTGGAAGAACGGCGCCGGATCCCA

AGCTGACCGTGTCCACGGCTGCAGCCCAGCAGCTGGACCCCCAAGAGCACCTGAACCAGG

GCAGGCCCCACCTGTCGCCCAGGCCACCCCCAACAGGAGACCCTGGCAGCCAACCACAGT

GGGGGTCTGGAGTGCCCAGAGCAGGGAAGCAGGGCCAGCACGCCGTGAGCGCCTACCTGG

CTGATGCCCGCAGGGCCCTGGGGTCCGCGGGCTGTAGCCAACTCTTGGCAGCGCTGACAG

CCTATAAGCAAGACGACGACCTCGACAAGGTGCTGGCTGTGTTGGCCGCCCTGACCACTG

CAAAGCCAGAGGACTTCCCCCTGCTGCACAGGTTCAGCATGTTTGTGCGTCCACACCACA

AGCAGCGCTTCTCACAGACGTGCACAGACCTGACCGGCCGGCCCTACCCGGGCATGGAGC

CACCGGGACCCCAGGAGGAGAGGCTTGCCGTGCCTCCTGTGCTTACCCACAGGGCTCCCC

AACCAGGCCCCTCACGGTCCGAGAAGACCGGGAAGACCCAGAGCAAGATCTCGTCCTTCC

TTAGACAGAGGCCAGCAGGGACTGTGGGGGCGGGCGGTGAGGATGCAGGTCCCAGCCAGT

TGCCACACCGCCTCCAGGAAGCAGAGCGTCATGCAGGTCTTCTGGCCAGAGCCCCAGTGA

GTGCCCACGGAGGCCCCCAGCACACCCAACGTGGCTTGATCACCTGCCTGTCCAGCTCTG

GTGGGCCAAGAACCCACCCAACAGAATAGGCCAGCCCATGCCAGCCGGCTTGGCCCGCTG

CAGGCCTCAGGCAGGCGGGGCCCATGGTTGGTCCCTGCGGTGGGACCGGATCTGGGCCTG

CAGAACTTCCCTGGCTCCTGGCCTGTGAGTGGTGCCACAGGGGCACCCCAGCTGAGCCCC

TCACCGGGAAGGAGGAGACCCCCGTGGGCACGTGTCCACTTTTAATCAGGGGACAGGGCT

CTCTAATAAAGCTGCTGGCAGTGCCC
(SEQ ID
N0:1).

The a bove-exemplified isolated DNA molecule shown in Figure lA-B and 2oSEQ >D I comprise NO: 4946 nucleotides, with an initiating Met at nucleotides 830 and on codon ucleotides initiating a "TAG" at n 4585-4587. Met and terminati The TAG termination codon are underlined.

The present invention also relates to biologically active fragments or mutants of SEQ 1D NO:1 which encode a mRNA molecule expressing a novel DNA helicase, 25 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 Figure 2 and as set forth as SEQ >D N0:2. Any such polynucleotide includes but is not necessarily limited to nucleotide substitutions, deletions, additions, amino-terminal truncations and carboxy-30 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
N0:2. 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 2o 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
3o 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 1o 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 15 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 2o 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 25 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 30 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 >D
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 carned out for 2 hours to overnight at 65°C in buffer composed of 6X SSC, SX Denhardt's solution, and 100 ~.g/ml denatured salmon sperm DNA. Filters are hybridized for 12 to 48 hrs at 65°C in prehybridization mixture containing 100 ~,g/ml denatured salmon sperm DNA and 5-20 X 106 cpm of 32P-labeled probe. Washing of 1o filters is done at 37°C for 1 hr in a solution containing 2X SSC, 0.1% SDS. This is followed by a wash in O.1X 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 carned out in SXSSC, SX Denhardt's solution, 50%
formamide at 42°C for 12 to 48 hours or a washing step carried out in 0.2X 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, New York.
2o 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 Figure 2 and set forth as SEQ ID N0:2. A preferred aspect of this portion of the present invention is a NHL protein which consists of the amino acid sequence disclosed in Figure 2 and set forth as SEQ >D N0:2, as follows:
MPKIVLNGVT VDFPFQPYKC QQEYMTKVLE CLQQKVNGIL ESPTGTGKTL CLLCTTLAWR
EHLRDGISAR KIAERAQGEL FPDRALSSWG NAAAAAGDPI ACYTDIPKII YASRTHSQLT
QVINELRNTS YRPKVCVLGS REQLCIHPEV KKQESNHLQI HLCRKKVASR SCHFYNWEE
KSLEQELASP ILDIEDLVKS GSKHRVCPYY LSRNLKQQAD IIFMPYNYLL DAKSRRAHNI
DLKGTWIFD EAHNVEKMCE ESASFDLTPH DLASGLDVID QVLEEQTKAA QQGEPHPEFS
ADSPSPGLNM ELEDIAKLKM ILLRLEGAID AVELPGDDSG VTKPGSYIFE LFAEAQITFQ
TKGCILDSLD QIIQHLAGRA GVFTNTAGLQ KLADIIQIVF SVDPSEGSPG SPAGLGALQS
YKVHIHPDAG HRRTAQRSDA WSTTAARKRG KVLSYWCFSP GHSMHELVRQ GVRSLILTSG

TLAPVSSFAL EMQIPFPVCL ENPHIIDKHQ IWGWPRGP DGAQLSSAFD RRFSEECLSS
LGKALGNIAR WPYGLLIFF PSYPVMEKSL EFWRARDLAR KMEALKPLFV EPRSKGSFSE
TISAYYARVA APGSTGATFL AVCRGKASEG LDFSDTNGRG VIVTGLPYPP RMDPRWLKM
QFLDEMKGQG GAGGQFLSGQ EWRQQASRA VNQAIGRVIR HRQDYGAVFL CDHRFAFADA
RAQLPSWRP HVRWDNFGH 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* (SEQ ID N0:2).
The present invention also relates to biologically active fragments and/or ~5 mutants of the human NHL protein comprising the amino acid sequence as set forth in SEQ )D N0:2, 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 >Z7 N0:2 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 N0:2 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 2o 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 1o 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 NHI.
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 2o 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 117 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 3o 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, New York. 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 >D 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 1o 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.l, pBIueBacHis2 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 3o 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
polymerise 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
sequences) 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 andlor 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), pMClneo (Stratagene), pXTI
(Stratagene), pSGS (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 3o expression vectors which may be suitable for recombinant NHL expression include, but are not limited to pCR2.1 (Invitrogen), pETI la (Novagen), lambda gtl l (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 pBlueBacllI 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;

1o 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), C127I (ATCC
CRL 1616), BS-C-1 (ATCC CCL 26), MRC-5 (ATCC CCL 171) and CPAE (ATCC CCL
209).

2o 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, SCUP and ARP (Figure SA). The nucleotide sequence of this BAC clone, hbm168, is presented as follows:

ACTGCACTCCAGCCTGTGTGACGGAGTGAGACTTGGTCTCP,~~AAAAAAAAAAGGAAACAC780 GTAAAAA.ATGGTTCTGACCCACAGAAATCTAAGAAAGGAAAAAATATAAAAAATAGAAAA1320 TAACATCCTAGAAAA.AAAGCTCCTACTCAGTGTTCATAAAGCAAAGCTAACCTACAGGAG2460 ACTCCAACTCP~AAAAAAAATAAAAATAACACACACGTGAATAGGCTCCTCATGGAAGTCA5640 GAAACTCCATCTCAAAAAAAF,AAAAAAAAAP,~~?~AAAAAAAAAGTTTAAAATGGTTAAATT10860 CCATGGTTGTGCCACTGCGCTCCAGCCTGGGCAACAGATCAAGACCTTGTCACAAAA.AAA11280 TCCGTCTCAAF,P.AAAP~AP~~AAAAAAAAAAAAAAAGAGATGGAGTCTCACTTTGTCAC19620 CAGCCTGGGCGACAGAGCCTCGAGACTCCATCTCAAAAAAF,AAAAAAAATTAGCTGGGTG21180 AGAGCGAGACTCTGTCTCAAP~AAAAAAAAAAAAAAACAAAAAAACAATAGTCTCCCAAGT21360 GCCACCACACTCCATCCAGCCTGGGTGACAGAGTGAGACTCCATCTCAAAGCAAA.A.AAAG22080 CCTGGGCGACAGAGCGAGACTCCGTCTCAAA.F~AAAAAAAACP,AAAAAAAAAAACAAAAAA23580 ACTCTTTCTT

ACAGAAAGAA

AGCAAGACTCCCGTCTCAAAP~1~AAAAAAAAAAATTTGTAGTGGTATGGAGGCCGGGCATG36720 CCTGGGCGACAGAGCAAGACTCTGTCTCAAP~~AAAAAAAAGAAAGAAAGAAATTAACTCT45780 ATAGAGCAGA

AAGCCCAGGAGTTTGAGACCAGCCTAGGCAACATAGGGAGACCCCATCTCP,~~AAAAAAAA59940 CTTGGCTCACTGCAGCTTCCGCCTCTTGGGTTCAAACAGTTCTCCTGCCTCAGCCTTCCG.60300 GGATCACACCACTGCATTCCAGCCTGGGTGACAAAGCGGGATTCTGTGTCF,F~AAAAAAAA62220 TCCAGCCTGGGCGGCAGAGTGAGGCCATCTCP,AAAAAAAAAAAAAGGAAAACTAAATATA63840 ATCTGGCATG

TACTAAAAATACAAAP.AAATTAGCCAGGTGTGGTGGTGCATGCTTGTAATCCCAGCTACT65940 CTCCTCTGTGGCATCTCCTTCCCTGATGGAAGCCGGGCGGGTGCC.TTCTCCTGCTGTATT69900 -$7--5 $-CAAGGCCAGGCCCCCCCACCCCCAGGAACTTCCCACAGTGGAGAGGAGGCCCAAGGCCAG92520' -~2-TGCCTGTAATCCCAGCTACTCAGGAGGCTGAGGCAGGAGAATCGCTTGAA.CCTGGGAGGC107040 CCGTCTCAAAP~1~AAAAAAAAAAAATGTCATCTCACTGCCTTCTGGTCCAATAGTTTCTGA108180 .

GCGAGACTCTGTCTCAAATAP~~AAAAAAAAAAAAAGGATAAAGAGTGTCTTCCATCCTTT110460 _75_ .

GTGAGACTCCATCTCGGGGAA.~~AAAA.AAAAAAAAAAATGCCATCAACAGCACGACCCTGG111120 GTTGCCTGGA

P~~AAAAAAAAAAAAAGAAAAGAAAAGAAATTAAGATCTAGACACTGTGGTTCATGCCTGT113460 _77_ TGTGCGTTCT CTA (SEQ ID N0:3) 114793.
The present invention also relates to a portion of SEQ m N0:3 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 ~ NO:1 begins at nucleotide 47095 of SEQ >D N0:3, the initiating ATG of human NHL is from nucleotide 48687-to of SEQ m N0:3, the termination 'TAG' codon is from nucleotide 84855-84857, while the 3' terminus of SEQ )D 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 ~ N0:3), which comprises the portion of the genomic clone encoding the mRNA transcript responsible for human NHL (see Figure 5A-B). The genomic sequence encoding NHL contains 35 exons (Figure 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 )I7 N0:3. As noted in regard to SEQ m NO:l, the present invention also relates to DNA vectors and recombinant hosts which comprise at least 2o a portion of SEQ 1D N0:3. 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 >D N0:3.
Therefore, the present invention relates to the isolated genomic sequence which set forth as SEQ 1D N0:3, a region of SEQ >D N0:3 which contains the coding and non-coding region of human NHL, as well as cis-acting sequences within SEQ m N0:3 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, SCUP
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 factors) 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 _78_ 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 carned 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 3o 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.
_79_ 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 1o 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 15 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 2o 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 25 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.
3o 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 1o 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.
15 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.
2o 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
25 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 3o 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.
t0 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 N0:2. Monospecific antibodies to NHL are purified from mammalian antisera containing antibodies reactive against NHL or are prepared as 3o 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 to 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 15 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 2o 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 25 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 30 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/NS 1/Ag 4-l; 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 1o 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 x 106 to about 6 x 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 15 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 20 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 25 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 30 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 HCI (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 (A2go) 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, 3o 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 3o 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 earned 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
2o 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 3o 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
_87_ 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.
_88_ 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 1o 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 15 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.
2o 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 25 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 30 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 to 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 a minor 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 15 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 20 309:255-258; 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 25 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 3o 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.

Characterization of DNA Molecules Encoding NHI.
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, 1o 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 N0:4) and C68.275R:
5'-CACAGTCCCTGCTGGCCTCTGTCTA-3' (SEQ ID N0:5), and E68.715F:
5'-CAGGACATCTCCATCAAGAGGCTGC-3' (SEQ ID N0:6) and E68.972R:
5'-AATAAGAGGGGGCCAGGATCAGTGC-3' (SEQ ID N0:7), 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 9min, 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.
3o A shot-gun library for BAC hbml68 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 CsCI 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 1o 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 ~5 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 carned out with SW480 polyA RNA
2o using standard conditions with TaqGold Enzyme at 94°C for l2min, 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 confrimation 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:
25 Junction of Exons Confirmed by Primers HOl/H02 hdkw (5'RACE) H02/H03 hdiy,hdiz H03-H09 hdid,hdie,hdja,hdjb H09-H 13 hdj a,hdie 30 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 N0:8);
HDIE - 5'-GTCTCCAGGCAGCTCAACAG-3' (SEQ ID N0:9);
HDIJ - 5'-ACCCTGTCCCTCCTGTCTGA-3' (SEQ ID NO:10);
HDIY - 5'-AGACCCTAAGATGTTCGGAG-3' (SEQ ID NO:11);
HDIZ - 5'-GATGACCTGTGTGAGTTGCG-3' (SEQ ID N0:12);
1o HDJA - 5'-CGCAACTCACACAGGTCATC-3' (SEQ ID
N0:13);

HDJB - 5'-GGAGTCAGGTCAAAGGATGC-3' (SEQ ID
N0:14);

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

HDJD - 5'-GGTCTGAAACGTGATCTGGG-3' (SEQ ID
N0:16);

HDJE - 5'-CCCAGATCACGTTTCAGACC-3' (SEQ ID
N0:17);

HDJF - 5'-CGATGATGTGTGGGTTCTCC-3' (SEQ ID
N0:18);

HDJG - 5'-GGAGAACCCACACATCATCG-3' (SEQ ID
N0:19);

HDJH - 5'-CGTGTCTGAGAAGTCCAGCC-3' (SEQ ID
N0:20);

HDJI - 5'-GGCTGGACTTCTCAGACACG-3' (SEQ m N0:21);

HDJJ - 5'-ACAGCATCTTCTCCACGCAC-3' (SEQ ID N0:22);

HFMU - 5'-AGTCCTCTGGCTTTGCAGTG-3' (SEQ ID
N0:23);

HDKV - 5'-TGTGCGTGGAGAAGATGCTG-3' (SEQ ID
N0:24);

HDKW - 5'-GGCTGGAAAGGGAAGTCTAC-3' (SEQ ID
N0:25);

HDND - 5'-TGGTTCAGGTGCTCTTGGGG-3' (SEQ ID
N0:26);

HDNE - 5'-CGTGAAGCAGGAGTTGAGCC-3' (SEQ ID
N0:27);

HDIK 5'-ATCTTGCTCTGGGTCTTCCC-3' (SEQ ID N0:28);
-HDIL - 5'-CACTGCAAAGCCAGAGGACT-3' (SEQ ID N0:29);

HDIP - 5'-ATAAGCAAGACGACGACCTC-3' (SEQ ID N0:30);

HDLI - 5'-CTATTCTGTTGGGTGGGTTC-3' (SEQ ID N0:31);

HDMV - 5'-CGTGCCTCCTGTGCTTACCC-3' (SEQ ID
N0:32);

3o HDNG - 5'-CAGACCCCAAGGTAGCTCAG-3' (SEQ 1D
N0:33);

HDNH - 5'-GGAAGACCCAGAGCAAGATC-3' (SEQ ID N0:34).

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 Figure 2, SEQ m N0:2) reveal an approximately 26% sequence identity and 48% sequence similarity to the RAD3/ERCC2 gene family of DNA
helicases (see Figure 3). Review of this sequence data shows that two partial human cDNA clones (Acc. No. a1080127 and ab029011) are deposited. No. a1080127 covers 1o exon 25-35 while ab029011 covers exons 9-35. Ab029011 starts at amino acid 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.

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 ~,g of polyA+ RNA were run on each lane a denaturing 2o formaldehyde 1% agarose gel, and transferred to a charged-modified nylon membrane.
The probe was made using a 733 by fragment derived from 1174-1907 nt of the NHL
cDNA. This fragment was labeled via the 32P dCTP random priming method (Ambion). Hybridization was carned 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 Figure 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.

Chromosomal localization To map the position of M68/NHI.. 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 20q 13.3, 28cR
from D20S 173 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, NJ) was arrested in mitosis with colcemid (10 ~.g/ml). A human chromosome 20 a-satellite probe (Vysis, Downers Grove, IL) was directly labeled ~5 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 2o Human Chromosome 20 probe. Radiation hybrid chromosomal mapping reconfirms that it is linked to M68 locus,at 20q13.3.

SEQUENCE LISTING
<110> APPLICANT: Merck & Co., Inc.
<120> TITLE: DNA MOLECULES ENCODING
HUMAN NHL, A DNA

HELICASE

<130> DOCKET/FILE REFERENCE: 20585 PCT

<160> NUMBER OF SEQUENCES: 38 <170> SOFTWARE: FastSEQ for Windows 4.0 Version <210> SEQ ID N0:1 <211> LENGTH: 4946 <212> TYPE: DNA

<213> ORGANISM: Homo sapien <220> FEATURE:

<221> NAME/KEY: CDS

<222> LOCATION: (828)...(4487) <400> SEQ ID N0:1 agtcagccct gctgccagcc agtgccgggt gctggggactcagggaggcccgccgggacc60 actgcgggac agtgagccga gcagaagctg gaacgcaggagaggaaggagagggggcggt120 cagggctctc aggagccggg tcctgggcaa ggcgcagccgttttcaaattttcaggaaag180 cggtcggctc acactcgagc agtaaaaaga tgcctctggggaggaggcccgtgcagctct240 ccgggcaatg gtggtggctc ggcctagaga ggcggtagtggaacgcagaccctggtgggg300 gaatgacatc aagggaggag acgggcggga ccccagatttctgcctgtgggcgatggaag360 tgaggttcac tggccagcgg agccggacac agaacgcgcaaaacgccgtgtaggcctgga420 ggagccgaag agcaggcgga ccccctccgc gggggaacagtttccgccgggagcacaaag480 caacggaccg gaagtggggg gcggaagtgc agtgggctcagcgccgactgcgcgcctctg540 cccgcgaaaa ctctgagctg gctgacagct ggggacgggtggcggccctcgactggagtc600 ggttgagttc ctgagggacc ccggttctgg aaggttcgccgcggagacaagtgagcagtc660 tgtgccatag ggattctcga agagaacagc gttgtgtcccagtgcacatgctcgcatcgc720 ttaccaggag tgcccgagac cctaagatgt tcggagtggttttttcgcacagacccgaat780 agcctgcccc tcagccacgc tctgtgccct tctgagaacaggctgat ccc aag 836 atg Met Pro Lys ata gtc ctg aat ggt gtg acc gta gac ttc cag tac aaa 884 ttc cct ccc Ile Val Leu Asn Gly Val Thr Val Asp Phe Gln Tyr Lys Phe Pro Pro tgc caa cag gag tac atg acc aag gtc tgt ctg cag aag 932 ctg gaa cag Cys Gln Gln Glu Tyr Met Thr Lys Val Cys Leu Gln Lys Leu Glu Gln gtg aat ggc atc ctg gag agc cct acg ggg aag ctg tgc 980 ggt aca acg Val Asn Gly Ile Leu Glu Ser Pro Thr Gly Lys Leu Cys Gly Thr Thr ctg ctg tgc acc acg ctg gcc tgg cga ctc cga ggc atc 1028 gaa cac gac Leu Leu Cys Thr Thr Leu Ala Trp Arg Leu Arg Gly Ile Glu His Asp tct gcc cgc aag att gcc gag agg gcg gag ctt ccg gat 1076 caa gga ttc Ser Ala Arg Lys Ile Ala Glu Arg Ala Glu Leu Pro Asp Gln Gly Phe cgg gcc ttg tca tcc tgg ggc aac get get get get get gga gac ccc 1124 Arg Ala Leu Ser Ser Trp Gly Asn Ala Ala Ala Ala Ala Gly Asp Pro ata get tgc tac acg gac atc cca aag att att tac gcc tcc agg acc 1172 Ile Ala Cys Tyr Thr Asp Ile Pro Lys Ile Ile Tyr Ala Ser Arg Thr cac tcg caa ctc aca cag gtc atc aac gag ctt cgg aac acc tcc tac 1220 His Ser Gln Leu Thr Gln Val Ile Asn Glu Leu Arg Asn Thr Ser Tyr cgg cct aag gtg tgt gtg ctg ggc tcc cgg gag cag ctg tgc atc cat 1268 Arg Pro Lys Val Cys Val Leu Gly Ser Arg Glu Gln Leu Cys Ile His cct gag gtg aag aaa caa gag agt aac cat cta cag atc cac ttg tgc 1316 Pro Glu Val Lys Lys Gln Glu Ser Asn His Leu Gln Ile His Leu Cys cgt aag aag gtg gca agt cgc tcc tgt cat ttc tac aac aac gta gaa 1364 Arg Lys Lys Val Ala Ser Arg Ser Cys His Phe Tyr Asn Asn Val Glu gaa aaa agc ctg gag cag gag ctg gcc agc ccc atc ctg gac att gag 1412 Glu Lys Ser Leu Glu Gln Glu Leu Ala Ser Pro Ile Leu Asp Ile Glu gac ttg gtc aag agc gga agc aag cac agg gtg tgc cct tac tac ctg 1460 Asp Leu Val Lys Ser Gly Ser Lys His Arg Val Cys Pro Tyr Tyr Leu tcc cgg aac ctg aag cag caa gcc gac atc ata ttc atg ccg tac aat 1508 Ser Arg Asn Leu Lys Gln Gln Ala Asp Ile Ile Phe Met Pro Tyr Asn tac ttg ttg gat gcc aag agc cgc aga gca cac aac att gac ctg aag 1556 Tyr Leu Leu Asp Ala Lys Ser Arg Arg Ala His Asn Ile Asp Leu Lys ggg aca gtc gtg atc ttt gac gaa get cac aac gtg gag aag atg tgt 1604 Gly Thr Val Val Ile Phe Asp Glu Ala His Asn Val Glu Lys Met Cys gaa gaa tcg gca tcc ttt gac ctg act ccc cat gac ctg get tca gga 1652 Glu Glu Ser Ala Ser Phe Asp Leu Thr Pro His Asp Leu Ala Ser Gly ctg gac gtc ata gac cag gtg ctg gag gag cag acc aag gca gcg cag 1700 Leu Asp Val Ile Asp Gln Val Leu Glu Glu Gln Thr Lys Ala Ala Gln cag ggt gag ccc cac ccg gag ttc agc gcg gac tcc ccc agc cca ggg 1748 Gln Gly Glu Pro His Pro Glu Phe Ser Ala Asp Ser Pro Ser Pro Gly ctg aac atg gag ctg gaa gac att gca aag ctg aag atg atc ctg ctg 1796 Leu Asn Met Glu Leu Glu Asp Ile Ala Lys Leu Lys Met Ile Leu Leu cgc ctg gag ggg gcc atc gat get gtt gag ctg cct gga gac gac agc 1844 Arg Leu Glu Gly Ala Ile Asp Ala Val Glu Leu Pro Gly Asp Asp Ser ggt gtc acc aag cca ggg agc tac atc ttt gag ctg ttt get gaa gcc 1892 Gly Val Thr Lys Pro Gly Ser Tyr Ile Phe Glu Leu Phe Ala Glu Ala cag atc acg ttt cag acc aag ggc tgc atc ctg gac tcg ctg gac cag 1940 Gln Ile Thr Phe Gln Thr Lys Gly Cys Ile Leu Asp Ser Leu Asp Gln atc atc cag cac ctg gca gga cgt get gga gtg ttc acc aac acg gcc 1988 Ile Ile Gln His Leu Ala Gly Arg Ala Gly Val Phe Thr Asn Thr Ala gga ctg cag aag ctg gcg gac att atc cag att gtg ttc agt gtg gac 2036 Gly Leu Gln Lys Leu Ala Asp Ile Ile Gln Ile Val Phe Ser Val Asp ccc tcc gag ggc agc cct ggt tcc cca gca ggg ctg ggg gcc tta cag 2084 Pro Ser Glu Gly Ser Pro Gly Ser Pro Ala Gly Leu Gly Ala Leu Gln tcc tat aag gtg cac atc cat cct gat get ggt cac cgg agg acg get 2132 Ser Tyr Lys Val His Ile His Pro Asp Ala Gly His Arg Arg Thr Ala cag cgg tct gat gcc tgg agc acc act gca gcc aga aag cga ggg aag 2180 Gln Arg Ser Asp Ala Trp Ser Thr Thr Ala Ala Arg Lys Arg Gly Lys gtgctg agctactgg tgcttcagt cccggccac agcatgcac gagctg 2228 ValLeu SerTyrTrp CysPheSer ProGlyHis SerMetHis GluLeu gtccgc cagggcgtc cgctccctc atccttacc agcggcacg ctggcc 2276 ValArg GlnGlyVal ArgSerLeu IleLeuThr SerGlyThr LeuAla ccggtg tcctccttt getctggag atgcagatc cctttccca gtctgc 2324 ProVal SerSerPhe AlaLeuGlu MetGlnIle ProPhePro ValCys ctggag aacccacac atcatcgac aagcaccag atctgggtg ggggtc 2372 LeuGlu AsnProHis IleIleAsp LysHisGln IleTrpVal GlyVal gtc ccc aga ggc ccc gat gga gcc cag ttg agc tcc gcg ttt gac aga 2420 Val Pro Arg Gly Pro Asp Gly Ala Gln Leu Ser Ser Ala Phe Asp Arg cgg ttt tcc gag gag tgc tta tcc tcc ctg ggg aag get ctg ggc aac 2468 Arg Phe Ser Glu Glu Cys Leu Ser Ser Leu Gly Lys Ala Leu Gly Asn atc gcc cgc gtg gtg ccc tat ggg ctc ctg atc ttc ttc cct tcc tat 2516 Ile Ala Arg Val Val Pro Tyr Gly Leu Leu Ile Phe Phe Pro Ser Tyr cct gtc atg gag aag agc ctg gag ttc tgg cgg gcc cgc gac ttg gcc 2564 Pro Val Met Glu Lys Ser Leu Glu Phe Trp Arg Ala Arg Asp Leu Ala agg aag atg gag gcg ctg aag ccg ctg ttt gtg gag ccc agg agc aaa 2612 Arg Lys Met Glu Ala Leu Lys Pro Leu Phe Val Glu Pro Arg Ser Lys ggc agc ttc tcc gag acc atc agt get tac tat gca agg gtt gcc gcc 2660 Gly Ser Phe Ser Glu Thr Ile Ser Ala Tyr Tyr Ala Arg Val Ala Ala cct ggg tcc acc ggc gcc acc ttc ctg gcg gtc tgc cgg ggc aag gcc 2708 Pro Gly Ser Thr Gly Ala Thr Phe Leu Ala Val Cys Arg Gly Lys Ala agc gag ggg ctg gac ttc tca gac acg aat ggc cgt ggt gtg att gtc 2756 Ser Glu Gly Leu Asp Phe Ser Asp Thr Asn Gly Arg Gly Val Ile Val acg ggc ctc ccg tac ccc cca cgc atg gac ccc cgg gtt gtc ctc aag 2804 Thr Gly Leu Pro Tyr Pro Pro Arg Met Asp Pro Arg Val Val Leu Lys atg cag ttc ctg gat gag atg aag ggc cag ggt ggg get ggg ggc cag 2852 Met Gln Phe Leu Asp Glu Met Lys Gly Gln Gly Gly Ala Gly Gly Gln ttc ctc tct ggg cag gag tgg tac cgg cag cag gcg tcc agg get gtg 2900 Phe Leu Ser Gly Gln Glu Trp Tyr Arg Gln Gln Ala Ser Arg Ala Val aac cag gcc atc ggg cga gtg atc cgg cac cgc cag gac tac gga get 2948 Asn Gln Ala Ile Gly Arg Val Ile Arg His Arg Gln Asp Tyr Gly Ala gtc ttc ctc tgt gac cac agg ttc gcc ttt gcc gac gca aga gcc caa 2996 Val Phe Leu Cys Asp His Arg Phe Ala Phe Ala Asp Ala Arg Ala Gln ctg ccc tcc tgg gtg cgt ccc cac gtc agg gtg tat gac aac ttt ggc 3044 Leu Pro Ser Trp Val Arg Pro His Val Arg Val Tyr Asp Asn Phe Gly cat gtc atc cga gac gtg gcc cag ttc ttc cgt gtt gcc gag cga act 3092 His Val Ile Arg Asp Val Ala Gln Phe Phe Arg Val Ala Glu Arg Thr atg cca gcg ccg gcc ccc cgg get aca gca ccc agt gtg cgt gga gaa 3140 Met Pro Ala Pro Ala Pro Arg Ala Thr Ala Pro Ser Val Arg Gly Glu gat get gtc agc gag gcc aag tcg cct ggc ccc ttc ttc tcc acc agg 3188 Asp Ala Val Ser Glu Ala Lys Ser Pro Gly Pro Phe Phe Ser Thr Arg aaa get aag agt ctg gac ctg cat gtc ccc agc ctg aag cag agg tcc 3236 Lys Ala Lys Ser Leu Asp Leu His Val Pro Ser Leu Lys Gln Arg Ser tca ggg tca cca get gcc ggg gac ccc gag agt agc ctg tgt gtg gag 3284 Ser Gly Ser Pro Ala Ala Gly Asp Pro Glu Ser Ser Leu Cys Val Glu tat gag cag gag cca gtt cct gcc cgg cag agg ccc agg ggg ctg ctg 3332 Tyr Glu Gln Glu Pro Val Pro Ala Arg Gln Arg Pro Arg Gly Leu Leu gcc gcc ctg gag cac agc gaa cag cgg gcg ggg agc cct ggc gag gag 3380 Ala Ala Leu Glu His Ser Glu Gln Arg Ala Gly Ser Pro Gly Glu Glu cag gcc cac agc tgc tcc acc ctg tcc ctc ctg tct gag aag agg ccg 3428 Gln Ala His Ser Cys Ser Thr Leu Ser Leu Leu Ser Glu Lys Arg Pro gca gaa gaa ccg cga gga ggg agg aag aag atc cgg ctg gtc agc cac 3476 Ala Glu Glu Pro Arg Gly Gly Arg Lys Lys Ile Arg Leu Val Ser His ccg gag gag ccc gtg get ggt gca cag acg gac agg gcc aag ctc ttc 3524 Pro Glu Glu Pro Val Ala Gly Ala Gln Thr Asp Arg Ala Lys Leu Phe atg gtg gcc gtg aag cag gag ttg agc caa gcc aac ttt gcc acc ttc 3572 Met Val Ala Val Lys Gln Glu Leu Ser Gln Ala Asn Phe Ala Thr Phe acc cag gcc ctg cag gac tac aag ggt tcc gat gac ttc gcc gcc ctg 3620 Thr Gln Ala Leu Gln Asp Tyr Lys Gly Ser Asp Asp Phe Ala Ala Leu gcc gcc tgt ctc ggc ccc ctc ttt get gag gac ccc aag aag cac aac 3668 Ala Ala Cys Leu Gly Pro Leu Phe Ala Glu Asp Pro Lys Lys His Asn ctg ctc caa ggc ttc tac cag ttt gtg cgg ccc cac cat aag cag cag 3716 Leu Leu Gln Gly Phe Tyr Gln Phe Val Arg Pro His His Lys Gln Gln ttt gag gag gtc tgt atc cag ctg aca gga cga ggc tgt ggc tat cgg 3764 Phe Glu Glu Val Cys Ile Gln Leu Thr Gly Arg Gly Cys Gly Tyr Arg cct gag cac agc att ccc cga agg cag cgg gca cag ccg gtc ctg gac 3812 Pro Glu His Ser Ile Pro Arg Arg Gln Arg Ala Gln Pro Val Leu Asp ccc act gga aga acg gcg ccg gat ccc aag ctg acc gtg tcc acg get 3860 Pro Thr Gly Arg Thr Ala Pro Asp Pro Lys Leu Thr Val Ser Thr Ala gca gcc cag cag ctg gac ccc caa gag cac ctg aac cag ggc agg ccc 3908 Ala Ala Gln Gln Leu Asp Pro Gln Glu His Leu Asn Gln Gly Arg Pro cac ctg tcg ccc agg cca ccc cca aca gga gac cct ggc agc caa cca 3956 His Leu Ser Pro Arg Pro Pro Pro Thr Gly Asp Pro Gly Ser Gln Pro cag tgg ggg tct gga ,gtg ccc aga gca ggg aag cag ggc cag cac gcc 4004 Gln Trp Gly Ser Gly Val Pro Arg Ala Gly Lys Gln Gly Gln His Ala gtg agc gcc tac ctg get gat gcc cgc agg gcc ctg ggg tcc gcg ggc 4052 Val Ser Ala Tyr Leu Ala Asp Ala Arg Arg Ala Leu Gly Ser Ala Gly tgt agc caa ctc ttg gca gcg ctg aca gcc tat aag caa gac gac gac 4100 Cys Ser Gln Leu Leu Ala Ala Leu Thr Ala Tyr Lys Gln Asp Asp Asp ctcgac aaggtgctg getgtg ttggccgcc ctgaccactgca aagcca 4148 LeuAsp LysValLeu AlaVal LeuAlaAla LeuThrThrAla LysPro gaggac ttccccctg ctgcac aggttcagc atgtttgtgcgt ccacac 4196 GluAsp PheProLeu LeuHis ArgPheSer MetPheValArg ProHis cacaag cagcgcttc tcacag acgtgcaca gacctgaccggc cggccc~ 4244 HisLys GlnArgPhe SerGln ThrCysThr AspLeuThrGly ArgPro .

tacccg ggcatggag ccaccg ggaccccag gaggagaggctt gccgtg 4292 TyrPro GlyMetGlu ProPro GlyProGln GluGluArgLeu AlaVal cctcct gtgcttacc cacagg getccccaa ccaggcccctca cggtcc 4340 ProPro ValLeuThr HisArg AlaProGln ProGlyProSer ArgSer gag aag acc ggg aag acc cag agc aag atc tcg tcc ttc ctt aga cag 4388 Glu Lys Thr Gly Lys Thr Gln Ser Lys Ile Ser Ser Phe Leu Arg Gln agg cca gca ggg act gtg ggg gcg ggc ggt gag gat gca ggt ccc agc 4436 Arg Pro Ala Gly Thr Val Gly Ala Gly Gly Glu Asp Ala Gly Pro Ser cag tcc tca gga cct ccc cac ggg cct gca gca tct gag tgg ggc ctc 4484 Gln Ser Ser Gly Pro Pro His Gly Pro Ala Ala Ser Glu Trp Gly Leu tag gatgtgccca gcctgccaca ccgcctccag gaagcagagc gtcatgcagg 4537 tcttctggccagagccccagtgagtgcccacggaggcccccagcacacccaacgtggctt4597 gatcacctgcctgtccagctctggtgggccaagaacccacccaacagaataggccagccc4657 atgccagccggcttggcccgctgcaggcctcaggcaggcggggcccatggttggtccctg4717 cggtgggaccggatctgggcctgcctctgagaagccctgagctaccttggggtctggggt4777 gggtttctgggaaagtgcttccccagaacttccctggctcctggcctgtgagtggtgcca4837 caggggcaccccagctgagcccctcaccgggaaggaggagacccccgtgggcacgtgtcc4897 acttttaatcaggggacagggctctctaataaagctgctggcagtgccc 4946 <210> SEQ ID N0:2 <211> LENGTH: 1219 <212> TYPE: PRT
<213> ORGANISM: Homo sapien <400> SEQ ID N0:2 Met Pro Lys Ile Val Leu Asn Gly Val Thr Val Asp Phe Pro Phe Gln Pro Tyr Lys Cys Gln Gln Glu Tyr Met Thr Lys Val Leu Glu Cys Leu Gln Gln Lys Val Asn Gly Ile Leu Glu Ser Pro Thr Gly Thr Gly Lys Thr Leu Cys Leu Leu Cys Thr Thr Leu Ala Trp Arg Glu His Leu Arg Asp Gly Ile Ser Ala Arg Lys Ile Ala Glu Arg Ala Gln Gly Glu Leu Phe Pro Asp Arg Ala Leu Ser Ser Trp Gly Asn Ala Ala Ala Ala Ala Gly Asp Pro Ile Ala Cys Tyr Thr Asp Ile Pro Lys Ile Ile Tyr Ala Ser Arg Thr His Ser Gln Leu Thr Gln Val Ile Asn Glu Leu Arg Asn Thr Ser Tyr Arg Pro Lys Val Cys Val Leu Gly Ser Arg Glu Gln Leu Cys Ile His Pro Glu Val Lys Lys Gln Glu Ser Asn His Leu Gln Ile His Leu Cys Arg Lys Lys Val Ala Ser Arg Ser Cys His Phe Tyr Asn Asn Val Glu Glu Lys Ser Leu Glu Gln Glu Leu Ala Ser Pro Ile Leu Asp Ile Glu Asp Leu Val Lys Ser Gly Ser Lys His Arg Val Cys Pro Tyr Tyr Leu Ser Arg Asn Leu Lys Gln Gln Ala Asp Ile Ile Phe Met Pro Tyr Asn Tyr Leu Leu Asp Ala Lys Ser Arg Arg Ala His Asn Ile Asp Leu Lys Gly Thr Val Val Ile Phe Asp Glu Ala His Asn Val Glu Lys Met Cys Glu Glu Ser Ala Ser Phe Asp Leu Thr Pro His Asp Leu Ala Ser Gly Leu Asp Val Ile Asp Gln Val Leu Glu Glu Gln Thr Lys Ala Ala Gln Gln Gly Glu Pro His Pro Glu Phe Ser Ala Asp Ser Pro Ser Pro Gly Leu Asn Met Glu Leu Glu Asp Ile Ala Lys Leu Lys Met Ile Leu Leu Arg Leu Glu Gly Ala Ile Asp Ala Val Glu Leu Pro Gly Asp Asp Ser Gly Val Thr Lys Pro Gly Ser Tyr Ile Phe Glu Leu Phe Ala Glu Ala Gln Ile Thr Phe Gln Thr Lys Gly Cys Ile Leu Asp Ser Leu Asp Gln Ile Ile Gln His Leu Ala Gly Arg Ala Gly Val Phe Thr Asn Thr Ala Gly Leu Gln Lys Leu Ala Asp Ile Ile Gln Ile Val Phe Ser Val Asp Pro Ser Glu Gly Ser Pro Gly Ser Pro Ala Gly Leu Gly Ala Leu Gln Ser Tyr Lys Val His Ile His Pro Asp Ala Gly His Arg Arg Thr Ala Gln Arg Ser Asp Ala Trp Ser Thr Thr Ala Ala Arg Lys Arg Gly Lys Val Leu Ser Tyr Trp Cys Phe Ser Pro Gly His Ser Met His Glu Leu Val Arg Gln Gly Val Arg Ser Leu Ile Leu Thr Ser Gly Thr Leu Ala Pro Val Ser Ser Phe Ala Leu Glu Met Gln Ile Pro Phe Pro Val Cys Leu Glu Asn Pro His Ile Ile Asp Lys His Gln Ile Trp Val Gly Val Val Pro Arg Gly Pro Asp Gly Ala Gln Leu Ser Ser Ala Phe Asp Arg Arg Phe Ser Glu Glu Cys Leu Ser Ser Leu Gly Lys Ala Leu Gly Asn Ile Ala Arg Val Val Pro Tyr Gly Leu Leu Ile Phe Phe Pro Ser Tyr Pro Val Met Glu Lys Ser Leu Glu Phe Trp Arg Ala Arg Asp Leu Ala Arg Lys Met Glu Ala Leu Lys Pro Leu Phe Val Glu Pro Arg Ser Lys Gly Ser Phe Ser Glu Thr Ile Ser Ala Tyr Tyr Ala Arg Val Ala Ala Pro Gly Ser Thr Gly Ala Thr Phe Leu Ala Val Cys Arg Gly Lys Ala Ser Glu Gly Leu Asp Phe Ser Asp Thr Asn Gly Arg Gly Val Ile Val Thr Gly Leu Pro Tyr Pro Pro Arg Met Asp Pro Arg Val Val Leu Lys Met Gln Phe Leu Asp Glu Met Lys Gly Gln Gly Gly Ala Gly Gly Gln Phe Leu Ser Gly Gln Glu Trp Tyr Arg Gln Gln Ala Ser Arg Ala Val Asn Gln Ala Ile Gly Arg Val Ile Arg His Arg Gln Asp Tyr Gly Ala Val Phe Leu Cys Asp His Arg Phe Ala Phe Ala Asp Ala Arg Ala Gln Leu Pro Ser Trp Val Arg Pro His Val Arg Val Tyr Asp Asn Phe Gly His Val Ile Arg Asp Val Ala Gln Phe Phe Arg Val Ala Glu Arg Thr Met Pro Ala Pro Ala Pro Arg Ala Thr Ala Pro Ser Val Arg Gly Glu Asp Ala Val Ser Glu Ala Lys Ser Pro Gly Pro Phe Phe Ser Thr Arg Lys Ala Lys Ser Leu Asp Leu His Val Pro Ser Leu Lys Gln Arg Ser Ser Gly Ser Pro Ala Ala Gly Asp Pro Glu Ser Ser Leu Cys Val Glu Tyr Glu Gln Glu Pro Val Pro Ala Arg Gln Arg Pro Arg Gly Leu Leu Ala Ala Leu Glu His Ser Glu Gln Arg Ala Gly Ser Pro Gly Glu Glu Gln Ala His Ser Cys Ser Thr Leu Ser Leu Leu Ser Glu Lys Arg Pro Ala Glu Glu Pro Arg Gly Gly Arg Lys Lys Ile Arg Leu Val Ser His Pro Glu Glu Pro Val Ala Gly Ala Gln Thr Asp Arg Ala Lys Leu Phe Met Val Ala Val Lys Gln Glu Leu Ser Gln Ala Asn Phe Ala Thr Phe Thr Gln Ala Leu Gln Asp Tyr Lys Gly Ser Asp Asp Phe Ala Ala Leu Ala Ala Cys Leu Gly Pro Leu Phe Ala Glu Asp Pro Lys Lys His Asn Leu Leu Gln Gly Phe Tyr Gln Phe Val Arg Pro His His Lys Gln Gln Phe Glu Glu Val Cys Ile Gln Leu Thr Gly Arg Gly Cys Gly Tyr Arg Pro Glu His Ser Ile Pro Arg Arg Gln Arg Ala Gln Pro Val Leu Asp Pro Thr Gly Arg Thr Ala Pro Asp Pro Lys Leu Thr Val Ser Thr Ala Ala Ala Gln Gln Leu Asp Pro Gln Glu His Leu Asn Gln Gly Arg Pro His Leu Ser Pro Arg Pro Pro Pro Thr Gly Asp Pro Gly Ser Gln Pro Gln Trp Gly Ser Gly Val Pro Arg Ala Gly Lys Gln Gly Gln His Ala Val Ser Ala Tyr Leu Ala Asp Ala Arg Arg Ala Leu Gly Ser Ala Gly Cys Ser Gln Leu Leu Ala Ala Leu Thr Ala Tyr Lys Gln Asp Asp Asp Leu Asp Lys Val Leu Ala Val Leu Ala Ala Leu Thr Thr Ala Lys Pro Glu Asp Phe Pro Leu Leu His Arg Phe Ser Met Phe Val Arg Pro His His Lys Gln Arg Phe Ser Gln Thr Cys Thr Asp Leu Thr Gly Arg Pro Tyr Pro Gly Met Glu Pro Pro Gly Pro Gln Glu Glu Arg Leu Ala Val Pro Pro Val Leu Thr His Arg Ala Pro Gln Pro Gly Pro Ser Arg Ser Glu Lys Thr Gly Lys Thr Gln Ser Lys Ile Ser Ser Phe Leu Arg Gln Arg Pro Ala Gly Thr Val Gly Ala Gly Gly Glu Asp Ala Gly Pro Ser Gln Ser Ser Gly Pro Pro His Gly Pro Ala Ala Ser Glu Trp Gly Leu <210> SEQ ID N0:3 <211> LENGTH: 114793 <212> TYPE: DNA
<213> ORGANISM: Homo sapien <400> SEQ ID N0:3 tgaagagctttgaccaagaggctgtgacgaggccctacgaggactctggctctcctcctg 60 ctaagcacacccaggcaggtgtcctggcagatgaggaccacatgcagagcctcggccagc 120 ccaccaatgcccggatatgcaagtgagcccagcctggaccccccggcgaggcccagcagc 180 accagcccaggcccgaaaaccttaagaaatgaccagtgtctgctgctttaagccaccaag 240 ctctgcggtggtttgttaggctgcaagcatggctaattcagaaactgccagaaacaagca 300 ctgctgtccccagcctgggacacacagcaccgcctctgcgtggggagagggcacaggcta 360 agggcacaaatgccatcccagacccggctcttgtgtgtggaaggggccactgtgccatga 420 ggcagaggaaaccttggcaggaccttatgccacagcaatttaaaagagaagaaacaggct 480 gggcgtggtggctcatgcctataatcccagcactttgggaggccaaggtggtggatcact 540 tgaggtcaggagttcaagaccagcctggccaatatggtgaaaccctgtctctacgaaaaa 600 tacaaaatttaggcaggcgtggtggcgggtgcctgtaatccctgctattcaggaggctga 660 ggcaagagatttacttgaacccaggaggtggaggctgctgcagtgagctgagatcatgcc 720 actgcactccagcctgtgtgacggagtgagacttggtctcaaaaaaaaaaaaggaaacac 780 atctgactagtgtgatctcgcaaggaacattccagacacagtggagctagaaggttcttc 840 tccaaacaaggaatccccaggggatcaaattgttttgcatcggccagacatggtggctca 900 agcctgtaaccccagtgcttcgggaggctgaggtgggaggactgcttgagtccaggagtt 960 caagactagcttgggcaacacagtgagagcccattagccaggcgtggtggcacatgcctg 1020 cagtcccagcactgtactaaaaatctacacggggccgggcatggtggcacatgcctgtag 1080 agtcccagctactcaggaggctgaggcaggacgattccttgaacccaggaggtcacggct 1140 gccatgagccgtgactgtgccactgcactccagtctgtgcaacagaacgagactctgttt 1200 cgaaaaacaaaaaatcatttcatgtctccagtttctccactggcaaaagactctgtcaag 1260 gtaaaaaatggttctgacccacagaaatctaagaaaggaaaaaatataaaaaatagaaaa 1320 tttaaaaaagagatggtctcagaataaagaccaacctgggctatggttgtcactcttccc 1380 tcacaccttagaaagctttctggccgcatctggccaaagggccaccctgccccatcttgg 1440 atcagtgaggtgccttcgaacaagccacctgccctggagcccgtcctgtcttgtctgcca 1500 ccgcacgctcagtaggggaggggaagtcgctaggttttagttcaccagtctctggatcaa 1560 gacgtgccataaccaagaagccccagccacacccagacccgatgtggccacaaggggtga 1620 gctgggaaggcccaggaaaaggcgggaggcggacgaatggaaatgtcattctgtggccac 1680 agaaatgatctcaacgttttgtaacttcctaccaagaggcagtcttagctctgcccttga 1740 accagcacttggtgatgtcgcttgcgtcaatcaaggcaacagaagtgagcaggaggccca 1800 ctttcctctgcaactgtgggcttacggggcaaagaagtccaggcctccaggtggaggatc 1860 acagaccgggcaaagcagaggagagccacccagccgagcctacctgtgcctcagactgcc 1920 tccctccagagacccctgtggccaaggccacccagaccagcaggtccttgccaagctgtc 1980 agctgacgacaggggttggtgaggccggcccagaccagcagaaccacgaaccaaccaaca 2040 gaattaaaaataataacaactatgtcttgtcttaagccactaagttttggatggtttctt 2100 tctttctttttctttttttttttcggagacgcagtctcactctgttgcccaggctggagt 2160 gcagtggcgcaatcttggctcactgcaagctctgccccccggattcacgccattcccctg 2220 cctcagcctcctgagtaactgggactacaggtgcctgccattgggtgttttcttaaacag 2280 caaaagaaaactgacacaatcataaacagagcaagcaagagaacttggcaattatttcct 2340 ctctacttctcactgttcttcaaagagttaactcaagcataagatgtgagcaaattcttt 2400 taacatcctagaaaaaaagctcctactcagtgttcataaagcaaagctaacctacaggag 2460 ccaccttccacagtgaccacaggaaaccaagacagcaagtgggacaccagcctccagggc 2520 actgcgccagccgtgcgcctgtgtctgccactgccctggtccgtcactgccaccagccgg 2580 caagacacccacagaggagagctctaagccacaactgtgtacgaagacaactgtgcagga 2640 ttttattactacaacatttttgttttcttttttttttttttttgagactgagtctcgctc 2700 tgtcacccaggctggagtgcagtggcacaatctcggctcactgtaacctccatctccctg 2760 gttcaagcaattctcctgctgcagcctcccaactggattacaggcgcccgccaccacgcc 2820 tggctaatttttgtacttttagtagagatggggtttcaccatgttggccagactggtctc 2880 aaattcctgacaagtgatccacccaccctggcctcccaaagtgctgggattacaggtgtg 2940 agccactgcgcctggcccatttttgtttatcaataaaaatgtacttaatgttgaactctc 3000 cacatttcaaatgggtaactccagtgtccttgatgctcctgcgacatgttcgtgagactt 3060 ctcttgggtgtgagagtctagcatgtgggtggtctggacaggagggggagggaagagtgc 3120 agagccgggcagggtaaagagaccccctaggatgtgaaggccgccctgcatttgtcagac 3180 tgggcaacacccactccatcagatggaccctggtatgggcggcaagccacctaggtgccg 3240 aggcaagagaccgagggcacgagctgttccggtgtaataaaatgcataaaataagaatag 3300 ttatactagatatagatcataaatatgattatatatgaatatcattcatcattagtttgt 3360 agcaattactctttattccaatattataataatccttgcctaagcataacctaggaaaaa 3420 ctaggaaatcataacctaggaaaaactaggccatacagagataggagctgaggggacata 3480 gtgagaactgaccagaagacaagagtgcgagccttctgttatgcctggacagggccacca 3540 gagggctccttggtctagcggtaacgccagcatctgggaagacgcccgttgccaagtgga 3600 ccgtggtctagcggtagcctcagtgtcaaggaaaaacacccgctacttagcaaaccagga 3660 aagagagtctccctttccccgggggagtttagagaagactCtactcctccacctcttgcg 3720 gagggcctgacatcagtcaggcccgcccgcagttatccggaggcctaaccgtctccctgt 3780 gatgctgtgcttcagtggtcacgctcctagtccgccttcatgttccatcctgtgcacctg 3840 gctctgccttctagatagcagcagcaaattagtgaaagtactgaaagtctctgataagca 3900 gaaataatggcgtaagcggtctctctctctctctcctctctctctgcctcagctgccagg 3960 aagggaagggccccctggccagtgggcacgtgacccacatgaccttacctatcactggac 4020 atggttcacactccttaccctgccgctttgtcttgtatccaataaatagcgcaacctggc 4080 attcggggccgctaccagtctccgcgtcttggtggtagtggtcccccaggcccagctgtc 4140 tttttcttttatctttgtcttgtgtctttatttctacactctctcatctccgcatacgag 4200 gagaaaacccaccaaccctgtggggctggtccctacaccctggctttgtagactggagcc 4260 taggcacgactcagctgctgtagtgaattgcgatcctccaaacccagcaaggcacctgca 4320 ggacatctggcccagtctcctcgttgagccagttcacgaaaaagagacttttctgagtga 4380 catgctaatgggcaatatgaggactaaatgggatggtctccaacttggacaaaccaacag 4440 taaaagccactttgcggggaaagaaacttttccttttttcttttttttgagacaggatct 4500 caccctgtcacccaggctgcagtgcagtggcatgaccttggctcactgcagcctcaacct 4560 ctctcaggctcaagcaatcctcccgcctcaacctcccatgcagctgggaccataggtgca 4620 tgccaccacacccaaataatttttatattttttgtagagacgaggtttcactatgttgct 4680 cgggctggtctcaactcctgggctcaagcaaccctcccacctcagcctcccaaagtgctc 4740 agattacaggcaggagccaccaggcctggccaacataggaagaaatttaaatttgaattg 4800 aatattagaagagatgaaaattcatcaacatggaaagacaaagatcattaactaaagcca 4860 aaccagaatggaagctgtgtgtacagtggggtctcatgctgggaacgcgaggggcacgtg 4920 cagggctccacggtgtggcgacgccccatgctccctttgtgggggttcatccagcggaac 4980 atgaggacctggggtgcttttcaacatgtacgtgagtttaataataaaaaggtttaagga 5040 aagaaaaattcatatgtttctatataaacagaacatctggaaagatctattctaaggtgt 5100 tgacagtaggaatctctaggtagtagtaatatggcctttttgaatttttgcttatcagta 5160 ttttctaattttctttttctttctaaataattctagctatgaaataattttctaccatat 5220 atattttgtaataaaaatggttatatttaattttttaaaggctgtacaaacttcctgata 5280 aaatggcaaattagacacacacatgtgggccgggtacagtggctcgcgcctgtaattcca 5340 gcactttgggaggctgaggcaggcagatcacctaaggtcaggagtttgagaccagcctgg 5400 ccaacatggtgaaaccccgtctctactaaatatacaaaaatgagctggatgtggtggcac 5460 acacctatagtgccagctacttgggaagctgaggcaggaaaattgcttcaacccgggagg 5520 cagaggttgtagtgagccgagatcatgccactgcactccagcctaggcaacaagagcgag 5580 actccaactcaaaaaaaaataaaaataacacacacgtgaataggctcctcatggaagtca 5640 tcacaacaatgcagagggaagagcttccaaagtgtaaacccagaagcgaggagcaggagg 5700 gtgcgcgcagacgcagagagcagcaaggtgcagactgagaggcggaggctggccgtgggg 5760 agatgactgatgctcagtttataccccaaatccgtaaatctagaggcctggcacatcaac 5820 tacctctgccagcaggaatgagggaaaggagggcaaccaaaagatgtcccaccctcaccc 5880 atccagctacctgccatcctcagccccactggcagaagaccctgagaggtggaggcaggc 5940 ccctgcctacaggaccctgagagctaggggaaggcgttatcctgaactgtgtcccccgta 6000 aaattcatatgttgaaggcctcatccccagtgtgactgtatttaaagatggggtcttcag 6060 gagataatttaaatgaggtcatataagttggccctcatccagtaagactttgaccttctg 6120 gtggtttttttttttttggagactgggtctcactctatcactcaggttggagtacagtgg 6180 cacgatcacggctcactgctgtctccaactcctgggctcaggtgatcctcctgcttcagc 6240 ctcctgagtagctgggactacaggtgcttaccaccgcacccagctggtggtgcattgtgt 6300 tttttgtagagatggggttttgccatgtcgcccaggctggtcctgaactgggctcaagtg 6360 atctgtctccctcggcctcctgcagtgctggaattacaggtatgagccaccgcgcctggc 6420 cgaccgtgaccttctaagaagtgaaagagaaagatctttctctctccctccctctccatc 6480 atgaggacacagcaagaagtcggccatctgcaaggtagaaagcgagtcctcccaacagct 6540 gaacctggcagaccctgatcttggacttcagccttcagagctgtaagaaaataactctct 6600 gctgttcaggccacgcggtctacggcagcccgagcagactaagacacacgccatctgggg 6660 agtcagaccagatcaggaagaaaggcctagagctcaggatactgaaggtcccaacccggt 6720 gctggaccagaccaccccggcagccgcggccacggagtcacggctcgggtgaggtgacct 6780 ggacaccatcccggcagccgcggccacggagtcacggctcgggtgaggtgacctggacac 6840 catcccggcagccgcggccacggtgtcacggctcggatgagatgactcggacaccacccc 6900 ggcagccgcggccacggtgtcagggctcaggtgaggagagttggatatgggactgggcct 6960 accccgaggctgcttccacccagacgcctgggtgggtgacacgaaagctgggctcagttg 7020 ggatcagagcagcctctccccaggtcagaaatgaccctgggctcctcacagtagccctag 7080 ggcaccatgagaaagctacgtggacttctctgaccaagggtcactgctgccacactactc 7140 attgcaggccatgtcagggctcagctgaggagacgtggacaccaccccagcagccgcggc 7200 cacggcgtcccaagggagggacttgggcactgcctctctgggcaagagtggggaggtgtg 7260 gggtgggagatgtctggaaacatcatggacacatgccgggaaaacacggaagctgtgcac 7320 caaggtgctgacaaaggaaaaaggagaatggaggtgtgaacatccagctagcaggtccca 7380 ctcagaaactcctgcatttccagacatggccaccagctctgtggatgagacaggggagga 7440 cagggtacctcacaccaggaacccacacaggtccatgtcttgctctgtgatcacacaaca 7500 gcctccaccaccctgacatgcaggagggaggtcaaagcctcgggtccaacaacaggctcc 7560 acagcaagggaagaaaggcaggaaggaactcagggccaggtcctcccaggcagcagctgc 7620 ctgcacgctgtccaccaagggaggtctgacctacaccgcacaggggttggcagtctagag 7680 tcgtcctctgtcaaacggtgagaaagtcaaaagctcatgctcagtgatatgctaggtcag 7740 catgaagatgccacacatgagacacagcaaggatgagaccaacgggaagactgccccaga 7800 ccagagccccagagccctctggggaggaagaataaggatggcagcctgggactgcccggg 7860 gctgactctgcctttatttcaccccagcagaggcaggagtgacaccggctcacagcagga 7920 gcagctctgccacctcctagcagttccacctacgggcagcaaaacaaagctggcagtttg 7980 ggcaaatgttagcgtttttgccaactaacatttgaatcggacatctggtacagagatgag 8040 gaagaaaacactcacagtttcatgaagactgtcaagaaaatcactgactcttcacttcat 8100 ttatgaaaggccagctctctgacatccctaccactccctctcacatgagaaatcacggcc8160 tttcaggacgtggagccacgtggccatgcaggtacgggaggcctccccgcagctgcagct8220 gggtcttctggtccccgtgccatttctgcttttcttcgctctctacttacacacacattt8280 gagtccagtctcagaagaactggaactagaaaaatcctgacacttgtcccttactacgtt8340 aatgccagctgtgccaaggacagcccaacccaagcccccatcagccccaatggcaccgag8400 gcccgagcttacccgtgaggggccaagttggtcgtcaccaacacggtcttcaccccctcc8460 acaccactgccgtccactgcagtgtccggagttgtcacaaccaccacctcctccatgtgc8520 acactcacgtcgggagtcgccatggctcagcggaaggggacgcccaggccagcagcgtca8580 gtcctccagggtcccaagtcctggaggaagcaaggcagggcacagggatggagtcatctc8640 cacatccacacaacatagcactcacaaaggcatctctaatcagctccaaagacccaccct8700 tgagtcccagactgctacctcctgacaaaaacgagcggcaacagaagggctactccaggc8760 tctggttccgagggcggtgtaagcgcactccacccgtttttcccactggataagccgaaa8820 cccttgggtagaaagcacagagccactccctccacgtggggctcagagcaggaggacagg8880 aggggcctggaattccaagcaacttccctggacgcaggctcccggcttgccagttcttcc8940 gtctctcctggcctgaactcaaagccagccccaatccctgaactgagtttcaggtgcaga9000 aagcactccaagaagtcctcgctggtctgtggaacgggaagggaaacccattcaagacag9060 aaagagaggagggaaacgccctgggtttttttgggtttttgggttttttttgagacggag9120 tctcgctctgtcgcccaggctggaatgcagtggcacgacctcggctcactgcaagctcca9180 cctcctgggttcaagtgattctcctgcctcagcctctccaattgctgggattacaggttt9240 caccatgttgcccaggctggtctcaaactcctgacctcaggtgatccactcacctcggcc9300 tcccaaagtgctgggattgcaggtgtgaggcaccatgcctggcctgccccgggtttaaaa9360 attattattattttgtctttcctggctttgccttcagcaagtccaacccctgctaaaacc9420 cggtgataatggctgtcctggcccaaaaagcttggagacaggggaatcttcctcctgact9480 aaaggaatggtggcccaagagtgtgggggctccctgttgccctctcactctccatcccct9540 acctagcacagggaacacaaaagcccctggtttccagccagagggcaacgagcctggagt9600 cagagtgtgggggaggcgacaagaggagaggggagaagagaggatggcacacagctgtgt9660 gtgagcgcctgggtcgtcccaagacagtctctacgtggtcctgaccctaaagggcaaagg9720 gaagaaaactgacctacaggataggccactgcccaggtctcagatgggccccagtggcgc9780 atatgggacagatccacagtgcactggaaagtctctaaaataaactggcctaagaacaca9840 gacacaggaacggggtgcaaaatttgcagcctgaacctaaccaggtcgatttcttgctat9900 gaaaaaaaaaagtctacattctctgtgaaacttaaaacaagacctagagtccatagcaca9960 gtagtcaaagcatccagaacacgatcaaacttcctggcaaagggtagtctggttgattct10020 caaaggaacaaatacacaagagaagctggctcttgaacgcagaatccagagactttcagg10080 tgctatcggaccagctccaagaggaaagcaaacattgtcaaccaagtggaaagaaaatct10140 tggtatagaaacaggagttataaccaaacagaaatgtgaaaattaaaaacgacaaccaaa10200 agaaaatacacaaagctgggatagtctcagctactcggaaggcggggctggaggatcgtt10260 tgagcctaggagattgaggctgcaatgagctgtgatcacaccaccgcactccagtctggg10320 caacagagtgagaactctctcaaaaaacgaaaaagaaagaaagtagaacagaagtgacca10380 ggggctgggggagggagtacagggagttgttctttaatgagtacagaatttctgtttggg10440 atgatgaaaagctctggaaatggacggcggtgatggctgcacaatcactgtggctgttct10500 gaatggtgctgaaccacacatttaaaaacagttaaaatgggctgggcgtggtggctcacg10560 cctgtaatcccagcactttgggaggcggatcgcctgaggtcaggagttcgagaccatcct10620 ggccaacacagtgaaatcctgtcttgactaaaaatactaaaaattagccaggcatggtgg10680 caggcacctgtagtcccagctacttgggaggctggggcaggagacctgcttgaacccagg10740 aggcagaggttgcagtgagccgagatcgtgccactgcactccagcctgggcaacaagagc10800 gaaactccatctcaaaaaaaaaaaaaaaaaaaaaaaaaaaaagtttaaaatggttaaatt10860 ttatgttatgtatattttaccgtaataaaaacactgtaatgctactataatagaatgact10920 cattaggattagatatagactagaaagtacagaatataaaaactttttaaacaaagaaaa10980 attttcatggccaggcatggtgtcacacctgtaatcccaggactttgggaggccaaggca11040 agaggaatgcttgagctcaggggtttgagaccagcctgggcaacacagcaacaccccatc11100 tctgctaaataaataataaaaaatagccaggcatggtggtgtgcacgcctgtagttgcag11160 ctactctggaggctgaggcaggaggatcacttaagcccaggaggtcaaggctgcagtgag11220 ccatggttgtgccactgcgctccagcctgggcaacagatcaagaccttgtcacaaaaaaa11280 agaaagaaagaaaagaaaaaagaaagaaaataaaatcttccagaacttttaaaatcatca11340 ttgttaatataaaaataacatcacctgcccctaggactgtaacaaacaagtgtgtctaag11400 gacaggagtgggtccaccccaacctggcacgcagtggtcccctgcggagagtctggccct11460 gcactcactaagaggaggcactcatagcccagccaggcctctgcaattatgccttcaatg11520 ccagaactaactcacccaaactgaacaatcgatcacaaaatgtgccttcaggtctcaagg11580 ttcttgctaaatcttactcaaccgacattttccagcatgggaacatttttctgaatgtct11640 tagggagaggaagtccgcaagagaacaaaaggtcctcaggccaccctagcttcttttcct11700 ccattccacaggctgtcttttgtctgggtatgcactggaccagggggctctacttcttcc11760 tacctgggcatgggtctccacacaactccaaggtaaagggccacaggcaagataaagggg11820 agaaaagaaagctacgatttcctgggccaccaatcgcaaatggcagccagtctctgaagt11880 aacccttgaccagagatccaaggaaccaagaaatgtaggtgatctgaacagaggggatgg11940 tggttaaacaccatgaaggaaagacccattctcaaagaaaaggaagcaaaaagaaaccgt12000 ggggagctgggtaccacccgcagcaaagaccccgcacgcgttactgacgccagcctggcc12060 tgggagagcagtgagtgtggcggacggtgagtggcggggagggctgtggtaggtttaggg12120 taagaaggggcagcgcccagagcccagagaacaccagtgagggctccacaggaacactac12180 tcaaagtattcacggaacacatctaaacacaagcactaaggactaagtgcgagggacaag12240 aaaatattccccgtttcctgtttcaggagggtatcgaaaatgagtgatggaaggaaaatg12300 tattgtttaaatgaggaaaaaaaatttttacaaattaagaacatcctggaacatgatgag12360 ccgtttactgtcactcaatttaaatggtggccatctaggacagagcgcctaaggggaaag12420 ggggctcacaggtgaacccctccagctgctggtgggcaatttcccattagggcatcaggg12480 tctctgaagactgtcttcagatgctttttagccaggaaagttacaatgatgaattcgttt12540 acactggcggaattacttcgtatttctcaaatataatgttttcactagcataactttgtt12600 gttgtagacttaggcttcaaaataaagaactttaaacaaacatgaataaaaagccacttt12660 aggccgggcgcggtggctcacacttgtaatcccagcactttgggaggccgcggcgggtgg12720 atcataaggtcagaagttcaaagaccagcctgatcaatacggtgaaaccccgtctctact12780 aaaaatacaaaaattagccgggcgcggtggcaggtgcctgtaatctcagctacttgggag12840 gctgaggcaggagaatcgcttgaacctgggcagcagaggttgcagtgagccaagatcatg12900 ccactgcactcaagcctgggtgacagagtgagactctctcttaaaaaaaaaaagccactt12960 taaaattttactcaggccaggtgtggtggctcacgcccataatcctagcactttgggagg13020 ccgaggcgagcagatcacctgaggtcaggagttagaccagcctggccaacatggtaaaac13080 cttgtctctactgaaaacacaaaaattagctgggcgtggtggtgtgcccatgtaatccca13140 gctactcaggaggctgaagtgagagaactgcttgaacccgggaggcagaggctgcagtgt13200 gccaagactgcaccactacacttcagcctgggcgacagagcaagaccctgtctcagaaaa13260 aaaaaaaattcaaaaatttggccaggcgtggtggctcacgcctgtaatcccatcactttg13320 gaaggccgaggcgggtggatcacctgaggtcaggaattcaagaccagcctggccaccatg13380 atgaaaccctgtctctactaaaaatacaaaaaaaaaaaaacaaattggccgggcatggtg13440 gcgggtgcctgtaatcccacctacttgggaggctgaggcaggagaatctctcgaactccg13500 gaggcagaggttgcagcgagccaagattgtgccactgcactccagcctagacaacagagc13560 gagactctgtctcaaaaaaaaaaaaattaaaattaaaaaataaaaatttcatttaaaata13620 ctactgatctcccgtgctgacttctcggggtttaactctcactgaggagacgctgctttc13680 ataagggtaagctcagcaggggcaactaaagtcatttaagcagagagctgcaaagaggca13740 acagcctcactgcaggcaggggtcctcgtcacagcttcagggctttgcagaggattacgc13800 aatgtacacgcacaaaactgaattccagcctctccattggcaactgcatacatacatata13860 ttctttttttgagacggagtctcgctctgtagcccaggttggactgcagtggcccgatct13920 cggctcaatgcaagctctgcctcccgggttcaagcgattctcttgcctcagcctcctgag13980 tagctgggattacaggcgcccaccaccacgcccggctaatttttgtatttttagtagaga14040 cggggtttcaccatgttggccaggacagtctcgatctcctgacctcgtgatccgcccgcc14100 tctgcctcccaaagtgctgggattacaggcgtgagccactgagcctggcctccaatggca14160 actatattaaaggttcaaagcaatatgcacaaaagttacctcacagaaaatagtgcaagt14220 ccttgatacaatgctctttagacacagaagaagcactatagaatagagcacctcgcccta14280 ttgccttcccaagggcgagcaccccctcctctctccacagctccttctttgtttttttga14340 gatggagtctcgctctgtcacccaggctggagtgcaatggcaaaatcttggctcactgca14400 acctccgcctcccgggttgaagtgattctcctgcctcagcctcccgagtagctgggacta14460 caggcacccaacacgcctagctaatttttgcatttttggtagagacggggtttcatcatg14520 ttggccaggctggtctcgaactcctgacctccagtgatcctcccaccttgacctcccata14580 gtgctgggattataggtgtgagccactacacctggcctctccacagccccttctgtgttg14640 aagccaagacccacccagctttgatcccaaggcttgggttccccactagtgtgaagtgag14700 tttccaaattattaggtaaatcagatatgagaaaatattttattttactttttttttttt14760 gagacgcaatcttgctccgtcacccaggctggagtgcaatggcaccatctccactcactg14820 caacctctgccttctgggttcaagcaattctcctgcctcagcctcccaactagctgggat14880 tacaagtgcacaccaccacgcccggctaacttttgtatttttagtagagacagggtttca14940 ccgtgttagccaggctgctctcaaactcctgacctcatgatccgcccacgtcgggctccc15000 aaagtggtgggattacaggtgtgagccatcacacctggcccaagaaaatatttttaaact15060 agtattcttgaccggcacggtcaacactgatgtaattgaaactgttgtatttgaagtgtt15120 agcaaagaaagagaattctggttcaacagaaaagtcagtcacgacttttcagtcacgcat15180 gaattacacagtaaccaaatagataacatgccatgactgacgacgggcccacaacaaatc15240 agctccgaccaacagggtccacaccaccatgggtctacacagatccaggtcccgcctgtg15300 agcctacagtgacgcgggcccctgtggggtggtccctgcaggtcaggtccctgagagtgg15360 gtcccagtggggtgatccctgcgggtcgcgtccctgcgagttgggtgcctgccgggtggc15420 ccctgcgggtcgggtgcctgcggggtggtccctatgggtcgcgtccctgcgggtcgggtg15480 cctgcggggtggcccctgggaatcgcgtccctgcgggtcgggtgcctgcggggtggcccc15540 tggggatcgcgtccctgcgggtcgggtgcctgcggggtggcccctggggatcgcgtccct15600 gcgggtcgggtgcctgcggggtggtccttgtgggtcgcgtccctgtggggtggtccctgt15660 gggtcgcgtccctgtggggtggcccctgcgggtcgcgtggtggcccctgcgggtcgggtg15720 cctgcggggtggtccctgtgggtcgcgtccctgcgggtcgggtgcctgcggggtggtccc15780 tgcgggtcgcacccctgcggcgtggtccccccgggatgggtccaccgaggaggccgctgg15840 aggccgagcccgcgcccgcccgcggcgccaagatggaggcaggaagcgccgccgcccgcg15900 cccgccaccgcccgcgccgcccgcctgacgccgccgttgcgcctgacgccgccgcccgcg15960 cggccgcccctcccccggccctcccctccccccgccgtaacgtcctgacgctccgcaggg16020 acccctgactggacggcggcgcgtgagcggagcgagaggcctcgccgcgggggggccgcg16080 ggctcgccggcgccgcttacctggggccgcgccgggcctgcttaggcacccggcgggggc16140 ggcggcgtcgggagctgcggcggcggcgggcggcggcggcggccgcgggcttcgctcctt16200 gttggggattcggcggcggcggcggcgcgggcgcgcgcttcctagtgacgcaggcggcgg16260 ggccgcgcacgcacggggctgggagggccggacacttatttggcgctcgcggaggaggaa16320 ggcggggccgtgaaataaggcccgacgggccccggggcgcgtgcgcggaccgacactgtc16380 agctcctaacgccgcaggttcctcctggtccccgaggcccccggtcgggcgttgcctgcc16440 ccgcgcgggcggccgggccgagggacgatggtcagtggacggacggcgccagggagcagt16500 gcccacgcgcggcagggcggtaccttcaggcctccaggtacgggcgctcctcgcccggac16560 gctgctgtgtgtgaatgggcgcgaggggactcccctgcggggcggacgcctgaacacgag16620 gctgtggaggaggacgctgtagggtgcgcggactcacgcggaacatgccagaggctcagc16680 cagccacggcgctcccagcgtggagggcgaggggcatccgggagcggccgggagggctcg16740 gtcacccctcaagctgtcaccccagtcccacaaccagcaccccgatcctatcgcagtccc16800 acagccgacaccccgatcccacccctgcccaacagccggcacccaccccaatcccatagc16860 taacaccccggtcccaccgctgtcccacggccggcaccccgatcccaccccagtcccgca16920 gctggcaccccgatcccaccccagcccaacagctggcacccaccccgatcccaccgctgt16980 cccacagccggcaccccgatcccaccccagtcccgcagccggcaccccgatcccacagcc17040 ggcactcaccccgatcgcatagcatagctgataccccgatcccaccccagtcccatagcc17100 agcaccccgatcccaccccagtcccatagccagcacctcgatcccatagatgacaccccg17160 atcacgccccagtcctatagcccgcaccccgatcccacccgagtcccgcagccggcaccc17220 catcccacccatgtcccacagtcggcaccccgatcccactcggatccggcagccagcttg17280 gatcctgtggccctcctccagcccccagggctcatttatatgttttattggcagaggctg17340 gggctggctctgttggcctctgtgctgggtttcttcctctgcaccgcaggactggctctc17400 ctgacctctccaggtgtcatcgaacacccttgtgcttgctgtcacccgctgcctgtctgc17460 aggatcccggattccgtatcaggggaccgaaattagtcggaaaataggaagcaggtgctc17520 gcttggatggaaccctgaccctgtgctcacacttgtaggaggagggctctgcaggccgcc17580 tcccggaacgggaggttcccaagccactgcacttcggaggggctgtaattagagttgcac17640 attcattcagttcccagtaaagtagaacgtgctccagccagtgaggaaaaggtgttttta17700 aaaattagattggccgagtgcggtggctcatgccttttacctcaacactttgggagacaa17760 aggtgggaggatcacctgtggccaggagttcaagaccagcctgggcaacagagcctgtct17820 ctggggaagaataaaaaaaaaaattgagcctttgtcagtgctactattttattatctggt17880 aaatatgagagggttcacgcggtctatgtgtgtcatttatctgagtttgcctatcgtcac17940 gttttggaaataaatgtcaataaagtcgaagaggagtgctgaggggggcctggggatggg18000 agggtggctacatcatgcctgtgtgttgcgcaagcccaccgaggtcggcctggggtgagc18060 cctggggcctgttctgcctccttcactctggggctccaagagacaaactgggcaacaaga18120 gagaaactccatctaaaaaaaaagaaaaatcacctccaagataacttagctttcttctgc18180 tggcataacaaattatctcaaacttagtcgcttaaaaatgcaaatttaggctgagtgcgg18240 aggctcacgcccataatcctagcactttgggaggccaaggcaggattgcttgaggccagg18300 agttcgagaccaacatggccagaactgtctctttttaaaaaatgcaaatgtgtccggcac18360 ggtggctcacgcctataatcccagcactttgtgaggccaaggcgggcagatcacgaggtc18420 aggagatagagaccatcctggctaacactgtgaaaccccctctctactaaaaatacaaaa18480 aattagcctggcgtggtggcaggcgcctgtagtcccagctactcgggaggctgaggcagg18540 agaatggcgtgaacccaggaagcggagcttgcagtgagccgagatggcgccactgcactc18600 cagcctaggcaacagagcaagactccgtctcaaaaaataaataaataaaactgcaaatgt18660 attctctaactgttctgtaggtcggaagtccagcccagcctcactccgccaaaatcaggg18720 tgtctgcagggccgattgcttttggagctccaggggagaagctgttctggcctttccagt18780 ttctggaagcacttgagccccttgtctcgtggcctatcccacacctgaaagccagccaaa18840 gccagttgagtcctcaccctgttggccccgacactgatctcctgcctccctcatctgctg18900 tcaaggccccttgtgatgacatggggccaccagctggcccagggcacctcctgtcagagt18960 ccgccgaccagtgaccttcattccatctgtcgctgtaattcccctttgcttggaaccaac19020 gttcacagatcccaggggttaggatgtgaatatcttgggcagggctgtgggggggctatt19080 cttccttctaaaatatttatcatttttgttttggggatttttttggtttggttttttttg19140 agacagagtctcgctctgtcgcccaggttggagtgcaatggtgcaatctcagctcactgc19200 aacctctgcctccgggcagacgtgagccactgcaccaggcctgtttttgtttttgtttgt19260 tttgttttgtttttgagatggagtctcggccgggcgcggtggctcacgcctgtaatccca19320 gcactttgggaggccgaggcgggcggatcacgaggtcaggagatcgagaccatcctggct19380 aacacggtgaaaccccgtctctactaaaaatacaaaaaattagccgggcgtggtagcggg19440 cgcctgtagtcccagctactcgggaggctgaggcaggagaatggcgtgaacccgggaggc19500 ggagcttgcagtgagccgagatcgcgccactgcactccagcctgggcgacagagcgagac19560 tccgtctcaaaaaaaaaaaaaaaaaaaaaaaaaaaaagagatggagtctcactttgtcac19620 ccaggctggagtgtagtggcgggattataggtacgcgccatcatgcccagttactttttg19680 tatttttagtagagacagggttttaccatgttggtcagactggtctcaaactcctgatct19740 caggtaatccacccgcctcagcctcccaaagtgctgggattacagacgtgagccaccgtg19800 tctggccatatttattaactacaaagggaaagatgataatttttttttttgagatggagt19860 ctcactctgtcacccaggctggagtacaatagcgtgatcttggctcactgaaacctctgc19920 ctcccaggttcaagcgattctcctgcctcagcctcccaactagctgggattacaggcgca19980 cgctaccaagcccagctaatttttgtatttttagtagaaacggagtttcaccatgttggt20040 gaggctggtctcgaactcctgaccttgtgatctgcccacctcggcctcccaaagtgctgg20100 gattataggcatgagccactgcaaccggctgaaagatggtaattttaaagtagagaaact20160 gggttggctgggcatggtggcttatgcctgtaagctcagcactttggaagtccaaggcaa20220 gaggatcgcttgagtccaggagtttgagaccagcctggacaatatagcaagaccccatct20280 ccgcaaaagctaaaaagttagccaggtgtggcggcacatgcctgtagtcccagctactca20340 ggaggctgacgtgggaggatcacttgagaccaggaggtcaaggctgaagtgagctgttat20400 tgtgccactgcactcagcctgggcaacagagcgagagtctgtctccaaaggtaaaaaaag20460 gtccaggcacagtggctcacacctgtaatctcagcactttgggaggccgaggcgggcaga20520 ttcgttgaggtcaggagttcaaaacgagcctggctaaatggtgaaaccccgtctctacta20580 aaaatacaaaaaaattagccaggcatggtgacgggcgcctgtaatctcagctacttggga20640 gactgaggcaggagaatcatgtaaacccaggaggctgaggttgcagcgagccaagatcat20700 gccactgcacttcagcctgggcgacagagcaagactgtctcaaaacaaaacaaaagaatc20760 ttgagtcctgagttcctctaagggaaattccaggcacctcgccacccttgacaggcaaag20820 gaacaatctgatgaggaagaagatagaaacagcttaaacaatagtctcccggccgggggc20880 agtggctcacgcctgtaatctgagcactttgggaggccgaggcgggtggatcacaaggtc20940 aagagatcaagaccatcctggctaacatggtgaaaccccgtctctactaaaaatacaaaa21000 aattagccgggcgtggtggtgggtgcctgtagtcccagctactcgggaggctgaggcagg21060 agaatggcgtgaacccaggaggcggagctttcagtgagctgagatcgcgcctctgcactc21120 cagcctgggcgacagagcctcgagactccatctcaaaaaaaaaaaaaaattagctgggtg21180 tggtggctcacacctgtaatcccagctacgtggcaggctgaggcaggagaatcgcttgaa21240 cctgggaggcggaggttgtagggagctgagatcgcaccactgcactccagcctgggcaac21300 agagcgagactctgtctcaaaaaaaaaaaaaaaaaacaaaaaaacaatagtctcccaagt21360 aagtcagagtcacaaggtgttttgattccctgtggaaactaaaatataacagcttaacat21420 atgttcttgagttatttttcagaaacttggacatccaccaggtggaaaatgctgagctag21480 gaacagtggctataatttcagccttttgagaggccaaggtggaaggatcacttgaggcca21540 ggagttagagaccagcctggccaacatggtgaaaccccgtctctagtaaaaatacaaata21600 ttagctgggcatggtggtgcaacctgaaatcccagctacttgggagacctagctgggagg21660 atcgcttgaacctggtaggaggagtttgcagtgagctgaaattgtgccactgcactctag21720 cctgggcaacagagtgagactctgtctcaaaaaataaataaataaaaagagaaaaaagtg21780 ttgcctgcaggccgggcacagtggctcacgcctgtaatcccaacactttgggaggccgag21840 atgggcagatcacctgaggtcaggagtgcaagaacagcctggccaacatggtgaaacccc21900 atctctactaaaaatacaaaagttagctgggtgtgtacatgtagtctcagctacttggga21960 agctgaggcaggagaatctcttcaaccggggaggtggaggttgcgatgagctgagatcac22020 gccaccacactccatccagcctgggtgacagagtgagactccatctcaaagcaaaaaaag22080 aaacataggtgggacccttggtgtgtccttagggcatgatggttgaggtatactgctggt22140 cctgtcatgtaaaagaaaacgagccgactctgtgtctactggagaaagcactgcatatat22200 cagccacagtcaatacctcgcttctgcagggacggtggctgccagagtgggaggctttgg22260 tagcacccatgtcgtggaatcacaatgttgtcgatagctctggggtcttgtacaaaatgc22320 cagatcctcccatttggtttccttatgggaaggatcgcagtactataatacatgggcttg22380 tgcaagggatcattatacccttttctctttttttgcttttctttgagacagagtttcact22440 ctcgtcacccaggctggagtgcaatggcgcgatcttggctcactgcaacctccacctcct22500 gggttcaagtgattttcctggctcagccttctgagtagctgggattacacatgcccgcca22560 ccaggcctgacttatttttgtatttttagtagagacagggtttcaccaagttggtcaggc22620 tggtcttgaactcctgacctcaggtgatccacccacctcggcctcccaaagtgttgggat22680 ttcaggcataagccaccaggcccagcctttctttctttttaaaattaatctttgtttaaa22740 aatactctcattttttatttaattgtagcactcctagatcccgaaagcagatacactctt22800 gttatgggtctgattcttttcattgcttcacgccttagaggatattgtccaatactggat22860 aaaagtttactcaggtctacttccactttaacggggatggctgaatatctcttccacttg22920 gctgtttgtttataatgaactgacaaacatacaaattttcttgagttctgtgagacattc22980 tagtaaatcatctaacctgaagagcaggttgtgagaacccctgatttagaaagcccagtg23040 gtcataaatataagtggctctggactggctcccggggtctgaagtgtgggcagtcggtta23100 ggattgagcccttgtaatttgtaggatctgacacacactccaggaaggcagtgtcagaat23160 ttacctgtattatattggacacccagttagcgtttggagaattggttgctggtatagaaa23220 aataccaaatattttatgtcaggggagtgaaagaaaaaacaaaaacccggccgggcgcgg23280 tggctcacgcctgtcatcccagcactttgggaggccgagacgggcggatcacgaggtcag23340 gagatcgagaccatcctggctaacacggtgaaaccccatctctactaaaaatacaaaaat23400 tagccgggcgtggtggcgcgcgcctgtagtcccagctactcgggaggctgaggcaggaga23460 atggcgtgaacccgggaggcggagcttgcagtgagcccagatcgcgccaccgcactccag23520 cctgggcgacagagcgagactccgtctcaaaaaaaaaaaacaaaaaaaaaaaacaaaaaa23580 aaaaaacccatacactttaaggaaagcaactgacagcatttgttaccagtgataaaattt23640 gagctttgaagtaagaataacaattttgccattgtgcccgggccaagaaaaaaaaaagaa23700 ttttgccattgtgaaaggcttcccagtactttctgatgagcttgacggtgatattaacaa23760 ataactttttttttttttttttgagatggggtcttgctctgtcacccaggctggagtgca23820 gtggttcaatctcagctcactgcaacctccgcctcccaggttcaagcgattctcctgcct23880 caacgtcccaagtcgctggactacaggtgtgcgccaccacgtccagataatttttgtatt23940 tttagtagagatggggtttcaccatgttgcccagactggtctcaaactcgtgacctcagg24000 cgacccgcccacctcggcctcccaaaggtgggaggccttgctgggattagaggtatgagc24060 cgctgcacctggcctcttgtccttgtgttttgcagtgatgcaatgaccatgtcttacatt24120 tgcaaccagaaaaaaaggttagtgtaacaatgtttatcctgtttttcccagagtagacat24180 tatgaagattaaaaaaatttgaaagtgttttgaatataataaactatgctatacacacaa24240 cattttggtgactagaaatacaagtttattgtttgttgtttgttgagacagggccctgct24300 ctgtctcccaggctgggtggcacaatcatggctcactacagtcttgaactcctgggctta24360 agcgatcctcccacctcagcctccagagtagctgggactgcaaacgagcaccaccacgcc24420 tggctaatatttgtattttttgtagagatggggtttcaccatgttgcccagactggtctc24480 aaactcctgggctcaagcaatgctcctgcctcggcctcccaaagtgctgggatcacaagt24540 atgagccactgcacccggctgagtttctgttgttttaagccgcttcatttgtggtacttc24600 ttacagcagtcccaggaaactgagcaactgcagaacatcaaaattgtttttcttcagcaa24660 aaggagaagcacttgtggttggcaccagcttttcctgtgctcacttctgcatggccgcac24720 ctttgcccgacacgagtgcacagcaggctgtgggggagcaactggttgagtcaggcctcc24780 acttgtgccgtatccccacctgctttgctggacacccctgtttggggggcacccactgct24840 gccccagacaccaagcaagcaccagctgtgtccaaaacttacagtcactgtcttggcccg24900 ttttgtgctgctgtaacagaatgccacagactgggtaatttaatacagaacagaaattta24960 tttcctcaaagttttggaggctgggaagtccaagagcaaggggccatcaggtcagggcct25020 ggtctctgcttccacgatggcaccttgaccaccgtgtcctcacgtggtcagagagagccc25080 actcccaggagcccttttaatagagcagaacactgctgcgctgcggttaagtttccaaca25140 cgtgaacttcggaggtgacacattcagatcatagcagtcactctaggcagagtgtctgat25200 gtggttttaaaatacgttcacagactggccgggcactgtagctcacgtctgtaatcccaa25260 cagtttgggaggccaaggtgggtggatcacctgaggtcaggagttcaagaccagcctcac25320 caacatggtgaaaccccatctctactaaaaatacaaaattagccaggtggtgcatgcctg25380 taatcccagctactcgggaggccgaggctggagaatcgcttgaatccaggaggtggaggt25440 tacagtgagtcgagatcatgccattgcactccagcctgggcaacaagagcgaaactctgt25500 ctcaaaaaataaaataaaataaaatacattcacaaggccgggcactgtggctcacgcctg25560 taatcccagctacttgggagactgaggcaggagaatcgcttataacctgggaggtggagg25620 ttgcagtgagctgagatcacaccgctacactctagcttgggcaacaagagtgaaactccg25680 tctcaaaaaagtaaaataaggccctgcaggcatggtggcccacacctgtaatcccagcac25740 tttaggaggccaaggcggtcggatcacgaggtcaggagttcgagaccagcctggccaaca25800 tgatgaaaccccgtctctactagcctagccaacatggggaaaccctgtctctactaaaaa25860 tacaaaaattagccgggcatggtggtgcgtgcctgtaatcccagctactcaggaggctga25920 ggcaggagaatcgcttgaacccaggaagcagagggtgcagtgagccaagattgcgccgct25980 gctctctagcctgggcgacagagcgagactccatctctaaataaataaataaaataagaa26040 aataaaatatgttcacaaatcctttgacattcctcacctcaaaagctggaacccaactcc26100 ctcctaagcatgagtcttctcagtgactcacttctaacagcagaacttacatggttcccc26160 acacccagaggacattgggttcctcccaatatccccccacccagcgacccccacccaggt26220 cgctggctttgggtcccccagagccatgtttcaaggacactcaggcagcccctggatgtc26280 catgtggtaaggaatgaaggcctcctgcctgcagcctcgggagggagcattctcagaaga26340 ggatgccccacctcctgcccagccttcagatggccaggacctcgtccaacgtcctgactg26400 caacatcatgagagactccgagccagaaacccccaggttttgtactcctgacttatggga26460 actgacagataatgttcgttgttaattaaggggtgacttgtcacacacaataggtcacta26520 aacagctctgtctggcctcccaggaggagcctgcctttccttttcttcatgggaaaagtg26580 cgatcagtttgtgaaggaatgtccgcccccacttgatgccagaggctccacatggtgact26640 gtcataaactccatctgccctcagtgccttgccagcacccggcctgcgatcagcttggtc26700 ttgcgggaggccaaggcccacgtgtgtttgtgtgtggtgtctgtgtctgcgtgcccatgc26760 atgcccagggtacagggatgccatatacaaattctttcaatgttgtatgtggcatgtgtg26820 tgtctgtatgcccaggatacagggatgctatatacaaactctgttttttcgttttttttt26880 ttttgagacagagtcttgctgtttcgcccaggccggactgcagtggcgctatctcggctc26940 actgcaagctccacctcccgggttcacgccatcctcctgcctcagcctcctgagtagctg27000 gaactacaggcgcccgccaccacacccggctaattttttgtatttttagtagagacgggg27060 tttcaccatgttagccaggatggtcttgatctcctgacctcgtgatccacccgcctcagc27120 ctcccaaagtgctgggattacaggcatgagccaccacgcctggcctacaaactctttctt27180 ttttttttttttttttttgagatggagtctcactgtcttccaggctggagtgcagtgatg27240 cgatctcagctcactgcaagctccacctcccgggttcatgccattctcctgcctcagcct27300 cccaagtagctgggactacaggcacacaccaccacgcccagctaattttttgtgttttta27360 gcagagatggggtttcaccatgttagccaggatggtctcgatctcctgacctcgtgatcc27420 gcccgcctcggcctcccaaagtgctgggattacaggcgtgagccactgcgcccagcctgc27480 aaactctttcaatgtctttcttttctctctcctgccatcttctcccttgcagatttcttt27540 tgtctctacgtcttccccagctgagtccgaggtcctgacttgcccacgctccctggactg27600 gaggagaggtgatagcaagagctccttcaagcccaggaatgccaccagggctgccccggg27660 agaggaggaagctgggtctctcggggttgtggggaccagacacccttctaagacatggac27720 tcagcacagaaagtctagacatccactacaaacacatctccctcctaacagggggcccct27780 gggcaccccaagtggctgtttggtgggacaggcatgtccatcagtcagaatatctttatt27840 ttttattttttattttttatttttgagagagtttcactggagtgcaatggcacgatctca27900 gctccctacaacctccgcctcccaggttcaagcgattctcctgcctcagcctgccacgta27960 gctgggattacaggtgtgagccaccacacccagctaattttttttttttttttttgagat28020 ggagtctcgaggctctgtcgcccaggctggagtgcagaggcgcgatctcagctcactgaa28080 agctccgcctcctgggttcacgccattctcctgcctcagcctcccgagtagctgggatta28140 caggcatgagccaccgcgcccggccaattttgtatttttagtagagacagggtttcacca28200 tgttggtcaggctggtcttgaactcctgacctcaggtgatccacctccctcggcctccca28260 aagtgctgggattacaggcctgagccaccacgcccagcccagaatgtcttcttacttttt28320 attactctgtcccccatcctgggtccagacctgtgaccgtgaacaaccggctgcccaggg28380 gtgaatggggtgagtggggtgagtccacagaacagtggggtgcagccccaggggtctcgt28440 agcacctgcccccaggtcaggaagtcccacagcctagaggctccagcctcagatgcatac28500 atatgtaggccctgccctttcctcctgagcggcgggccacagagtcctgaacaacaggaa28560 gcccctgaggagggctccgccctgagggagggcaggggagcccccgccagccccacccac28620 agcagcgggccctgccaccccccaccctgacacctcaccccttggattccagagaggaaa28680 gtgggcttgtgtgtagtttacatgctcatatcttaaaatcaccgttgtcaatagaacaat28740 tcataataatgatgataaaataagatttataaccagcttcagtctggagatacacacaga28800 gcagatcttcactcccagacagggagcccgcagctgcccccgaccccacaggtgcaggac28860 acacacagacagttcaaccatgtcttaaacacacaggtgtttatttaattgttcatttga28920 ttgaatttttaagttcactttactacgtggatgagatgggtgcatattacagtaggcttt28980 cgctatgagcgctgccaccatgaggaatatcccagccctcagttctgcttccctttctga29040 gtcccacaaaagccagatgtggacagccttgggttcccatcccagctggctgctccttct29100 ggggctgtcttggtggggagagggagatggggcagtgggtccctgctgacccctgagccc29160 tgcaggggtcaggatcctcccgtggtccctgggtgtggctctggaagacactggcagtgc29220 ccggccaaggcctcccgcaggatggaagttgagggccctggctctgggtcctaagagaac29280 tcagccgcccccttcacactttacagcaaggggccaggcagcagctttgggatggggctt29340 ccgtggagaagtgggggatgctgcagtggtacaaagacagcctcccccaccgccatcctc29400 cagctgaccgtcctccaaggccagcactgggcgtccaagggaaagaaggaactcagccca29460 gagggtgtgggcaggagaggcctggagtcaggcctccacccacagccccctctgggtgcc29520 aagtgggaagggtgttggggctggcttgggaaccttacccgctgcccttccaacacctgg29580 atctgtgggcagcggtcccacaaaatcccccttggggctccctgaggaggacttgtggct29640 gccgcttccaccagggcagagggcacaggaggggccagcactccaaagggctctagggtg29700 ggtctttcaaggacatctgcaaagccctggtggggaggggcctgggccagaggctctttg29760 gaactcttgcacttctgagtgggggactgtccatgctgcccacaacctctagaccatgca29820 gcctgctcatgggtccctggcagagaatgcccactccccagcagactcagggcaggcccc29880 caactgcaggcttccaggaaggcccagggtgtccacctcacgccaggtggtctcagagga29940 cccctgtgcaaccacattaaggaaagctgcagcccccacccacccgcctgccagttcaac30000 aagcaccggctgcacacgcaggctcccaggcaccatcacccccctcccccgtcgcccctc30060 cctcacggggagccccttccccctggaaagacagcaggtactgtagcctcgcctgctggc30120 caggggcgccggctcagaggacctgccctgacctgcacgtgctgaccagacagcccagcg30180 taaggacccgcgatcccacgccaccgccctgggtttaccacggtcaccaccacctctctc30240 acagggcccccgggggacccagccgcgcccggcctggtgtctgcaccgagggaccgcgtc30300 tcacgcccggcggctcctgcaggggaagccgtggtcagcgactcaccacgaggacagggc30360 agggcggctgagtgcggaagagaagcatgaagctgggggcgggggtgggggaggaggaac30420 aaaagttgcatctagacagaggtgaacgaaacaaaaccaaaacccgaacgtgttccgtcg30480 caggatgggcgccgcccgtcccgggcccttagcccgacatctcttctcgctgctccttgt30540 tcctgcgcacctcggccgcgtgcagctcctgcaggacagggggcgggagggcctgagggc30600 gggggtggcttggggcgactccgggaacccccaggcgcgcaggccgtggcgccctggcac30660 ccgcccggcctcatccgggctggccttcggcaggaccctgactgagttgagggggcggga30720 gcaccggggaggcgcagagcaaggccagggaccaaggacgggtttcctgggagctggctg30780 ggccccgcttctagctcgtaccggagccgagcttccttcagggcactttcaatataatga30840 atttagccatctattactgcggctagttactgtcccgccaggaccagactctggacctgc30900 ctcgtgcgctgctggggacgcccagtaaacacgggaggagcccccgacccccaccccagc30960 tcagcgcctcggagtccccggccccgctctgcgcccctccgagctccgccctagccccgc31020 ccccgcccagtgccccgccccctgcctgctgctagccctgcccccgccccggcccctgcc31080 cgctccgagctccgccctggccccgccccggcccctgcccgctccgagctccgccctggc31140 cccgccccccgcccagtgccccgccccctgcctgctgctagccctgcccccgccccggcc31200 cctgcccgctccgagctccgccccggccccgccccggcccctgcccgctccgagctccgc31260 cctggccccgcccccgcccagtgccccgccccctgactgctgctagccctgcccccgccc31320 cggcccctgcccgctccgagctccgccccggccccgcccc,ggcccctgcccgctccgagc31380 tccgccccggccccgccccggcccctgcccgctccgagcttcgccccggccccgccccgg31440 cccctgcccgctccgagctccgccccggccccgcccccgcaccttctcgcgcagccgctc31500 gcgcagtgcggccaggtgtgcctcgcggatctccttgctgagctccatcttgtagttgag31560 cttctcctccgcctggcggctgaagttgttattctcctccagcgccttgtgcagcacctc31620 gcgctcgtgctcgcgccgctccgccagctgcttcagcacctgcgcctcctgcgtctgtgc31680 ggggccggcgggcgcgcgtgagcggcaaccccgggccctgcccggccggactcctccctg31740 ctctccgcctcccgcccagcgcccgctcgcctcacctggcgcctccacctgcccaggcct31800 cggtgggcgccgggacccccgggcgctgccctgggaaccctcgcctgccatccggcctgt31860 ggtcggggcagggccagggggtcgcgatccgccgcccccgcccccgtccctgcctcgcgc31920 gcgggtcccgcggtcctggctgcgcccagggcccccgccataccctgccgccactgcaca31980 ccctgccctgcgcgtctgcccctccaaggaccagcagcaagaaaccctaaacttgtgggc32040 ggtctctgagctttgtctcttcctcggacatccgcccactgagcagagtagctgcttgtt32100 acacaccgggttcccagctcccaattaggtgcccaggagcggagggtccccagggatgct32160 gggggaggggccggctggtgacccctgggaggagagcggggcagcaggacccgcacccac32220 atgccagtccctactagtcagccctgtgaaccctggtctctggcctcaccgggaagggaa32280 cggagccgcttcccctgcccaatgcgttggcctccagggtggcacccccaaaaggacatt32340 tttatctctgtttcagtctcagaggggctggtgggaggggaggctgcagggaggggacct32400 ggagcccacacccacctctcccagggcccctccgccctccagcaagcctcagggtcttca32460 cacatgaggcccttcctccagcttccctgtctgggagagggatgccccacccgacgtccc32520 cagggcccatctggggaccaccccctagcatcctgctggccctgacaagggtgcctccca32580 ccctcaccagaggctcctgctccttccaggtggccgcctcggaacccttcctcctctcca32640 tccctttctttttttgttcttgtttgttttttgaaatggagtctcaccct_gtcgcccggg32700 ctgaggagtgcagtggcgcagtctcggctcactgcatcctccacttcttgggttcaagca32760 attcccctgcctcagactccctagtaggtgggattacaggtgtgcaccaccacacctggc32820 taattttgtatttttagtacagatggggtttcaccatgttggccaggctgatcttgaact32880 tccaacctcaagtgatctgcctgcctcagcttcccaaagttctgggattacaggcgtgag32940 ccaccacacccggcctctccccatcccattcttatctctcagaaagaggcccagggagcc33000 acagcccctcctgctccaggccaaggcactgaccaagcctgtccgggagcaccctgcttc33060 ttgcaggccctgtccccgtgggccgcctccgttgaaactcctggggggtgggggatggag33120 gactccttgccttcctccgctcctcggctgcctccagccgcttttgcagctcctccaggg33180 aggtgtccttcttcttgggtggggaggagagcatagggctctctggggacaggtcagaag33240 gggacttgaggatgacctcgaagctctggcctgaggcccgcttgtccagctgcttcacct33300 ccatgtctgcagggcaagaccagagtagagcttcagaggcccggccagggcatggcgtgg33360 gctgagcgggatgctcccagcacacatccaaccccagggctgggcgagagggggtggctg33420 ctcccgcaggaatcccaggcttcagcccccaggatgggccccttccccctagaacctccc33480 tctccagaggcagccaggacgggagttcagagagactgccggaggccgggggaaaaggtg33540 aggtgggcaggcaccgcagggaagggcaggcggcagccaggcactcacccccgtactggt33600 agacggtattggggtgcggctgtgtgtagaagcaggagcagatgagcgacagcaccgaca33660 gctccttcatcttctccttgtaggctgtgggcacaaggctgggctgagcaagcaccactg33720 gggcctgcccacctgggcccccgttttccc.tccccatggctgcctctatcatgtctctgt33780 gagacacggagctgcccagcacgctctcttgtgtgtctccacaccgccggCCCCttCgtC33840 tctccagctctctcgcttccagacgtcggcactgtctccgtggtgtgtcccctgccttct33900 gtctctctcgccctctgcctctccccgcttttcctctctctcggcattaatgtctgtctc33960 atcttccacactgacttgtttctccatccttctcctgcctgctgtggtctgaatgtttcc34020 attacccaaaactcatgtgttgaaatcgtaaccccaaggtgccggtgtgcggaggtgagg34080 cattcggagggaattaggccatgaggatagagccctcctaagtggccccagagtggggct34140 tcagagaactccctcaccttccatcatgtgaggacacagccagaagacgccacccgtcta34200 tgtaccaggaggcgagacctctccaggcaccgactctgccggcaccttgatcctggactt34260 tctggcctccagagcgatgggaaataagttcctgtcgtctataaaccactcagtctcagg34320 tacctgcccagactgacaaagtggctacccctgcctgtctgggtctctgtttaccttctg34380 tgtgtctgactctgtcactgtcattgtatctttctgtgtctctgggggtagcccctgact34440 ctgtctttctccctgagtgcatctttctgtgattccttgtcactgtgtgtctttctgact34500 cttacctccctctgtcccgctacttctctctcccctcctcctccttcccactcctcgcca34560 gctcaagcaggcaagatttactcatgacgggaccagcacagatgcaaaccctctgtgggc34620 aggactttcttgggctgtaaacctggatgaagccctcagaccctcctttttccttcccaa34680 tgattgtgtggtcaccttgagatgaaaccaggccctctccaggcacatgctctctgtcta34740 tctagggctgggcttgggccactgatgccaccaaggagcaagggagggaagctgtccgtt34800 cagcaccacagccagccctcttgcccattcaggtcaatcaagtgcccaccagccagtgtc34860 cctgctgcccaacccaaaccagaagcaagccgggctcctgtggccctgtgccctgtcagg34920 ggaagaggaaggcgcctgctgtcacagtgaaaataatttagctcttttggtctattcagg34980 gcgaacctcattcctaagcagacacgctggcccggtttctcactagtgctcgataatcct35040 tttggctgggtgcagtggctcatttaactgtaatcccagcactttgggaggccaaggcag35100 gtggaacacctgaggtcaggagtttgagaccagcctgaccaacatggtgaaacccgatct35160 ctactaaaaatataaaaattagccaggcgtggtggcaggcacctgtaatcctagctactt35220 gggaggctgaggcaggagaatcgcttgaacctgggaggcggaggttgcagtgagccgagg35280 tcgcgccatcgcactccagcctgggtgacagtgtgagactccgtctcaaaacagaaagaa35340 aaagagagagaggaagaaaggaaggagggagggagggaggaaaagaagaaaggaaaggaa35400 aggaagacagacaaggcagaagtaatcaagcctttcatggtgagctgggtcttctggtga35460 cagtgcagagaatggtctgtcctgacttaaatttcctggtgacctacacttttctggaca35520 gagcagcacagagcccaagagggtgtaaggaggagcagaaaggaatcccagggtgggcag35580 gcccgtgcgagagcctttgggggaaggaatgagactttgagccgggaagcgaggcaaagc35640 tacctgtcttggtcattgtcttcagggagggagatggagggggaccaggtgggggagcct35700 cacaggggactttggtctgacttgtcaagttttctttttttctttttgagatggagtctt35760 gcactgttgcccaggctgcagtgcagtggtgcgatctcggctcaccgcaagctccgcctc35820 ctgggttcacaccattctcctgcctcagcctcccgagtagctgggaccacaggcaccgcc35880 accacacccagctaattttttgtatttttagtagagacggggtttcactatattagccag35940 gatagtctcgatctcctgacctcgtgatccgcccgcctcgacctcccaaagtgctgggat36000 tacaggtgtgagccactgtgcctggcctactttattttttagaaacaggactgtgctctg36060 ttgcccatgctggagtgtagggtgcagctgtgcggttcactgcagccttgaacttctggg36120 cttgacggatcctgccatcttagcagctgggactacaggtgcatgccagcacaccagttt36180 tctttttttttttatctctgctcactgcaattccgcctcctgggttctagcgattctcct36240 gcctcagcctcccaagtagcagggattacacgcacatgccaccacacccggctaattttt36300 gtatttttagtagagacagggtttcactatgttggtcaggctggtcttgagccaccgcgc36360 ccgcccggcctacacaccagcttaaaaaaaagaaaaaaatagctgggcgtggtggctcat36420 gcctgtaatcccagcactttgggaggctgaggcaggcagatcacctgaggtcaggagttc36480 aagaccaacctggccaacatggcgaaaccctgtctctactacaaatataaaaatcagcca36540 ggcgtggtggcgggctcctctaattccagctacttgggaggctgaggcaggagaatcact36600 tgaacccgggaggtggaggttgaagtgagccaagatcgagctactgcactccagcctggg36660 agcaagactcccgtctcaaaaaaaaaaaaaaaatttgtagtggtatggaggccgggcatg36720 gtggctcacgcctgtaatcccagaactttgaggggccaaggcgggcagatcatgaggtca36780 ggagttcgagaccagcctgaccaacatgatgaaaccctgtctctactaaaaataacaaaa36840 attagccaggcatggtggcgggcacgtgtagtcccagctactcgggagactgagacggga36900 gaatcgcttgaacccaggaggcagaggttgcagtgagctgagatcacgccactgcactcc36960 agcctgggtgacagagtgagactctgtctcaaaaacaaacacaaacaaacatatatatat37020 atacatgtatatatataatatatatatacgtatatatacacgtgtatatatataatatat37080 atacgtatatatacacgtgtatatataatatatatacgtatatatgtatatattaatata37140 tatacgtatatatacacgtgtatatattaatatatatacgtatatatacacgtgtgtata37200 tattaatatatatacgtatatatgtgtgtgtgtgtatatatatatgtatatatatatata37260 tatatacatatatatatacagagagagagagagtagtgataggtcttgctgtcttgtcca37320 ggctgatcttgaactcccggcctcaagagaccctcccacctcagcctcccaaagcactag37380 gattataggtgtaagccacagtacctagcctattaaaaattaatgttaaacaagaggatg37440 tgatgagggagttagagggtgtgccagccatgtgttccacagcagcaggtcaggagacat37500 tggggacatttagaggagctgaagaggtggccaaccctgtgctcaggaggacgggggagg37560 gagagagcaagagggagtttgggctggggcagaacgtacctgggtcctgagaggataaga37620 aggtagggacttggcccctccaggcctgactctgccagcaaccagctccctatcagcaga37680 ctccaggcccctacccttcagctcatccttccttatcacacatccaaaactctgaatgtg37740 gccgggcgcagtggctcacgcctgtaatcccagaactttgggaggctgaggcaggaggat37800 cgcttgagaacaagagtttgagaccagcctaggcaacatggtgaaaccccatctctacta37860 aaaatataaaaattagctgggtgtggtggcacatgcctgttgccccagctactcaggagg37920 ctgaggcaggagaatcacttgagcctggaaggcggaagttgtagtgagcagagattgtgc37980 cactgcgttccagcctgggcaacacagcgagactctgtctcaaaaaacaaaaactggaat38040 gtgtttaccataaaggccagaaaatgtgattaacagctgctcaaagcccctgtctgccct38100 aagcctgaaattttcaccgaaaaaaagatctgtaggctcatacagaggaaggacaaacac38160 cagggaggctctcttccagtttgcttcacctcagcaagcagacggctggcagcaatttgg38220 gggcaggtgtgagcacctgcatcatcaggaaagaaggggcacggtggggacgcaggtcag38280 acctctcacaggtcttggctctgcccaggagacacgtgtccaactgagaggtgaggaact38340 gggttctgcagctgcagacacaggtgcggctcagcatctgatggccacggagaccccctg38400 gcttggcttctcccagctggtggcccatgaggagcttctatcccaagagactgtccctca38460 aggagcaagtgggaccaggtacccacaggacggagcctgggagtgaggcctgccctgtgg38520 tctggctacagggaggaagggcagattggagggggcaggacagcaggtcaggaattggcc38580 aactctggagagagcaagcaaggggaagtctgcgcacagggcagggctggtcaggggcga38640 ggcagggcattggaccagtattttcagagctggtgaggcttaaagagcatgtctactgcc38700 tcttattacagagagaggatgccgaggcccagacccatccaggccacctctccacagaca38760 cagctggtgccagggaagcccctcccagagcctcaaggcattgctccctctctctctctc38820 tttttgtttttttggagacggagtctcactctgtctcccaggctggagtgcagtggtaca38880 atctcggctcacggcaagctccgcctcccggattcacgccattctcctgcctcagcctcc38940 cgaatagctgggactacaggcgcccgccaccacgcccagctaattttttgtatttttagt39000 agagacggggtttcactgtgttagccaggatggtctcgatctcctgaccttgtgatccgc39060 ccgtctcagcctcccaaagtgctgggattacaggtgtgagccaccgcgcctggacttttt39120 tttttttttaagacggggtctcactctgtcacccaggctggagtgcagtggcgcgatgtc39180 ggctcactgcaacctctgcctccccagttcaagtgattctcctgcctcagcctcccaagt39240 agctagaattacaggcacatgccaccatgcccagctaattttctgtatttttagtagaga39300 tgaggtttcaccatgttggccaggctggtcttgaactcctgacctccggtgatctgccca39360 cctcagcctcccaaagtgctgggatgacaggcgtgagcccccgcgcctggccccccgcag39420 tgctgggattacaggcgtgagcccccgcgcccggcccctccctctctttgactcccttct39480 ttctcaccgccccctccccaccatccttccccttcactgacttcagggagttaaaaacaa39540 ttctcgcagtgagctgggcttgttttgtctccctgcttctctttgtactaaacattagat39600 accgaggaaatgcggattggcctttggatgattcatgagcaggagtcagaaaaaggcacc39660 aggttggcctcaagcagcagggtatagtagtgcccgctcccagggtcacacctcacgccc39720 acccctcccgccgtccaggtggatggtgcccactcccagggtcacacctcacgcccaccc39780 ctcccgccgtccaggtggatggtgcccactcccagggtcacacctcacgcccacccctcc39840 cgtcgcccaggtggatggtgcccactcccagggtcacacctcacgcccgcccctcccacc39900 cacccgggtggatggtgcccgctcccagggtcacacctgacgcccacccgggtggatggt39960 gcccgctcccagggtcacacctcacgcccacccctcccgcccgcccgggtggatggtgcc40020 cgctcccagggtcacacctcacgcccacccctcccgccgtccaggtggatggtgcccact40080 cccagggtcacacctcacgcccacccctcccgccgcccaggtggatggtgcccactccca40140 gggtcacacctcacacccacccctcccgcccacccgggtggatgcccttatcagctctcc40200 ttctccttctctttcgtcttcttcgtcttcctcctcttctttcttctttttttttttttt40260 tagaaagagtttctactcttgctgcccaggctggagtgcaatggcacaatctcagctcac40320 tgcaacctccctctccccgggtcaagcaattatcctgcctcagtctcccagattgctggg40380 atcacaggagtgtgtcaccacacctggctaattttgtacttttagcagagaggggggatt40440 tcaccatgttggccaggctagtctcgaactcttgacctcagtttatccaccggcctcagc40500 ctctcaaagtgctgggattacaggcatgagccaccctatctgcctcacttctacagagga40560 ggaatgaaggctcagagagggcaagcattccacccagcatcacacagagtgccgggtgag40620 agcccagtcatgagcctgggcctgactgcaggctcctgttgggagctcgcggaggtgggg40680 gatctgtccagaactgagaggccaggggaccacagtggcctctgacccctggagggccct40740 ggaggctgctgccggctccccccgggggcagatggaggtcactgtcacccaggctgcttc40800 tcatggtgccaggagcacagcatggcaggagccaccagccgatttgcctttccctgggca40860 ggaaactcagaaatgtggctaccacagtcaggctgcttgacgtgcggtgagcactcatct40920 cttagcaggcaagcggccaagcacctttcctgaaatattgaggcctcagaacaagcccca40980 ggagaggtgccagcaccgtcatctctacccagataaggagacccaggtcctgagaggtta41040 ggcagctcggacaacaccacacagctggaggaggtcagactctgggttgcagaaggagaa41100 tgtgagcagaggccacaaaagagcgaggagccagtgcccagatgccgagatgccctcgcc41160 ctcccagctcagccccaggaaccgagcccatggggagggaccgtcagggaaaggctgtca41220 ggaagggcaggaggcggccctggagaggacggcgctgccctcaggggcaggaggggagtc41280 ccctccgctgagagcccccccacccccagtatccccgggggtgtccaggaggaggcggag41340 ggaggaagcgcagatggacaggactcccagatagggtggggaggtgtggccggtgacaca41400 cacggtcccctcctggcaggtgctgaagtcacctggagcctccaagcccgtggggcctga41460 ggggcggggtcaggtcgggcacgcgtgggtgggcggagttctgcgccccgggccaaggcg41520 cccgagttgaaccagtcagctcgggagagggaccgcggcgacctgtcccgggggcgtaag41580 aaaaggtgggagggagtgcggctcgtgaacgggggcggcgatgggaaggaggtgcggccc41640 ttcgtcctgtcctcccaaacgtcgagtgaaaaacgaagcgggttctgcggcctcgcggcg41700 gagcagagcgtttcgggaagggcgggcccagcgtcctcgcgcccgaggtcgcccggcagc41760 tcccctgcgtccagaatccgccccccgcccgggcctgcgcccgcccctccgcctgagctc41820 cgcgcgggacgggccgggaggccggggtgggcgctaccttcgaaggcggtgggtccgccc41880 cgcgggaggtggaggggcgggaggggcggagccctctggtctccggagggtttggggatc41940 gcagtcgcccctCCCCCatCCagaCCCCgCggcgcaaagggcagtggcttttctggccag42000 agcaggtggcgcgggcgtcgcaaagggtggtccccgaggccgcagcggtgtggggggagg42060 gcgcggtccccctcactccgggctccgccgtgtctggcccgcccccctccttcagcgccc42120 cctccagcccctgtgctgcactggcgcggggagcgccgggttcccggctggggctttggc42180 agagggtcccaccctctccccgcctccccacgaaggctctggcggacccagatctcgggt42240 cgccggacgccccagggaccccgcccgcacatcgcgagcgcgcccacccggtcgcgagcc42300 cacgcccgggtctgggagccaccctgcggcagtcgcgccctgcgtggcacgctgctcccc42360 caggggcgaggcgcccccgcccgacgtcccggtcccgagcgctccccggcgcggcgcctc42420 gcagcccagcgccccaccagccccgccggcgccgcagaccccagcctcgggcgggtcggg42480 cccaggcttgcaacgcgcagggtaggagaagggaaattggcgtccgctgccggccgctgc42540 cccaggcgaggccagacgaggcctctgctcagatcccgccgccccacaaagcccgtggcc42600 ccggagcctaccggaaatggtgctggccatggtgctggcggcggttgggcctgcggaggc42660 tggagaggcgcaagtggcggccggagctgcagacggctggtgctgcagtgccggggaggg42720 gaggggagaggagtggagggagcgagggcgggcgggaggcgggcgcggcgggagagagag42780 agggagggagacagagggagagagagagagggttgggggaaggagcggggggaggaggga42840 gggagggttgggggaaggagagagagagagagagagactgcgggggcgggggaaggaggg42900 agggaggaagggagggaggaagagagagaggagcaagcgcctggctgcggaaggggccgc42960 ggctctcagggggagagggcggaggaggggggctacccgaactgcaacaagaCCCCCCaC43020 cctccaaccgctcacagcgggacagctgcttctccaacttggctttgtgaggcctgagag43080 tggggtgggggtggagatgagcccccattccccagggcaggcggggcaggggcaatgccg43140 gaggagcaggtcccacccatggggtggggccgcagagctcttcgccgccaaggccgctgt43200 aggctgggctggcgccaacagggtccaggtctgtgcctgccatcggagaggatgccacag43260 ccacaggggtgggcgctggcctggaggcctccaaggggcatctcctgtgagcccagggga43320 tgggcaggatctgagcggagaagagtgaaagtggaggagtgaggccagaacaaaggcttt43380 gccgtgaaagaggtggtttcccgcctgggctcagaccttcactcactgtgtggcccaggc43440 caagggcaagcgtctgacctcgctgggcctttgtttctcaggggtaagatgaaacaatga43500 tgcccccagacgatggagaggaggggtgccagggttgtgcgcacttagtgagtggggggc43560 aacctatcctgcctccccctctcctcataactcccaaagggaaagcctggtaggcaaacg43620 gagcgtctttgccattgcagggatgaagccaccgaggcagggagaaaagtgctttgccct43680 acaagcaactaagtcatagggccaggagcaaaaccctgaaaacctcaggagacttgcaga43740 gccatgaggctggctcagcaacacaaaagccaggggcaagcctcagctctagcagtgcgg43800 tgggagcacccaaggccagtcacatcctagggtggcctggagagtcctgacccctgacgt43860 gcaagccggcatcatccccgggactgtgagtctggtgggggtgatgcccaggaatgtgac43920 attgtgtggcccagaggtacccttaagactggaggatcaccaggcgggccctgacctcat43980 cacaggagccctttaaaagcagtttcctttgcctggttgaagaaatcggagggatcaaac44040 caaagaaggttttctgttgttgagatgagggggccacgtggcaaggatctgagaactgct44100 cccagccaacagccagcaagacaacaagaccttaactgcaaggaagtgagttctgccaac44160 aagaagagaatgggcttggaggcaggtttgaccccagggcctccacacaagaactgagcc44220 caactgcccacttggtttcagccttgggttactaagaattaggaggtaatgaatgagagt44280 tgttttaagctgttggttttgtggtgatttgctatgaagccatatcaaactaatatacac44340 acagaggtgttggcccctgggccattcctaggaagccagctctgcgaaggaggaagaagg44400 gcagagaggcacacagagctgcccaccacagcagctgtgtcctccctgttggccaccaca44460 gtagcagttggggatggtcagcatccttcaggcagactccagccccgggtgctggagctc44520 aggtgctagggatcaagagaagtagccctctctgggacctccagagtcttctcatgtggg44580 tggggtaggacccacccagtcaggctcagagcaccgcaatgcctcacactcattgtgact44640 ctggccaggccctctctgagcctctgtgtcctcatctggagcacagggaccaggtgtgtg44700 gaagcccgtggcatagtgccaggaacacagtagatgtgcacagtgtgcac.tagcaggaac44760 acacaacaggggtactgactgtcagcacctaggcaggcacacgcaatggggtactgactg44820 tcagccatactgactgtcagcgtgctagcaggcatacacaacagctgtactgacagcaca44880 ctagcaggcacatgccataggtgtactgactctcagtgcactggcaggcacacgcaatag44940 gagtaatgacagcatgctggcaggcacacaatagctgtactgactgtttgccccaatata45000 gtgccaggtcttggagcagattttgacttctcaccaagatcaaatgcagaaagtgcacga45060 gcatttcaaagatgtttttcacatgcacattagtgctagttaaaaaaatgttttgactgg45120 gtgcagtggctcacaactgtaatcccaacactttggggggccgaggtgggcagatcacct45180 gaggtcaggagtttgagaccagcctggccaacatggtgaaaccccatctaccctaaaaat45240 acaaaaattagccaggtgtggtggcaggtgcctgtaatctcagctactttggaggctgaa45300 gcaggagaatcacttgaatccaggaggcagaggttgcagtgagccgagatcccaccactg45360 cactccagcctgggcaacaatatcaagactccacctcaaaaaaaaaaatgtttttcataa45420 agtgtgacttttatcagacctctgcattcttgaaattaactctggcttggctgggcgtgg45480 tggcccacacctgtaatcttaacactttgggaggctgaggtgggcagatcacgaggtcag45540 gagttcaagaccagcctgaccaacatgatgaaaccccatctctactaaaaatacaaaaat45600 tagccgggcgtggtggcatgcacctgtaatcccagctactcaggaggctgaggcaggaga45660 atcgcttgaacccaggaggtggaggttgcagggagccgagatcgcaccactctattccag45720 cctgggcgacagagcaagactctgtctcaaaaaaaaaaaagaaagaaagaaattaactct45780 ggctcctagaaggagccctatatctcagcaggacactcagtcattcaacagacatctgtc45840 aagcacctgctgtatgctggagctgtgggtacgtcagcaattagaggaagagggcagggg45900 tacaggagttcctgaccaccccaggccagcacgctcctatagcagctggcaaggagcaga45960 tgactcagacttcagctcagtccacaggacagccttttctggccactgctctcaggagat46020 gagatgtgtggctgcaaaaggtaaactcctggctcctgagcaggctctgggcaatctgct46080 caacgctctgtgcctcactttctcacccagaaagtgtggacaatgagaggacttatctgg46140 ctgggcgcggtggctcacgcctgtaatcccagcactttgggaggccgaggcgggtggatc46200 acctgaggtcaggagttcaagacctgcctggccaacacggtcaaactccatctctactaa46260 aaatataaaaaattagccgggcttagtggtgcacacctgtaatcccagctacttgagagg46320 ctgaggcaggagaatcacttgaacccaggaggtggaggttgcagtgagccaagattgtgc46380 cactgcactccagcctgggcaaaaagccaaaactctgtctcaaagaaaaaagaatcatgg46440 cagaaggtgaagtctatgttagtcccagttcccaggtcgtacatggcggcaggagaaaga46500 gagagagaaggggaaactgccacttttaaaccatcgggtctcctgagcactcactgtcag46560 aacagcctggaggaaactgaccgcatgatccaaccacctccctccaggtccctccctcca46620 cacgtggggattacaattcgaggtgagacttgggtggagacacagagccgaaccatatca46680 gcatgtatggggggcactgaaacttgtgcttggtgcccattcattcaacgagtgtgtgtg46740 gctggtctcctcatcttcaactccctgccgagtctcagataggcagcctgcagttccttc46800 accacaacaggcacatggggctgggtgccagtgagtgctggggcttctccgagcactatc46860 tcacacccaggagcgtgggcacgcatggcattcgcatgtgccgtcagtggacattaaaca46920 cagccatgaagaagccacgaagaagtgctgcctgccggccgtgcgcggtcacgcagcgcc46980 aactccctcctggggccttctggggccttctggggcatgggagctggggccgcctgagac47040 aaacatccgtgacgctgggctgaccccacagaacggtgcgggcctcgctcttggagtcag47100 ccctgctgccagccagtgccgggtgctggggactcagggaggcccgccgggaccactgcg47160 ggacagtgagccgagcagaagctggaacgcaggagaggaaggagagggggcggtcagggc47220 tctcaggagccgggtcctgggcaaggcgcagccgttttcaaattttcaggaaagcggtcg47280 gctcacactcgagcagtaaaaagatgcctctggggaggaggcccgtgcagctctccgggc47340 aatggtggtggctcggcctagagaggcggtagtggaacgcagaccctggtgggggaatga47400 catcaagggaggagacgggcgggaccccagatttctgcctgtgggcgatggaagtgaggt47460 tcactggccagcggagccggacacagaacgcgcaaaacgccgtgtaggcctggaggagcc47520 gaagagcaggcggaccccctccgcgggggaacagtttccgccgggagcacaaagcaacgg47580 accggaagtggggggcggaagtgcagtgggctcagcgccgactgcgcgcctctgcccgcg47640 aaaactctgagctggctgacagctggggacgggtggcggccctcgactggagtcggttga47700 gttcctgagggaccccggttctggaaggttcgccgcggagacaagtgagcagtgagtcgc47760 agtgaccctacaagtggttcttttacccgagcggctcgtaggcgcgttgcggtttttcga47820 aactacagctcccggcaggccccaagccgccctcggggccgcgggtcggcggattggccg47880 cgctgcattttgggacctgtagtttcctgcgctcgtggcgctggcgccgcggcgttggct47940 gagcccttgaccggggctggagggaagggccgacattcagtgtgtccgcgtctgttctgt48000 tagtcccagttcccgggcgggattgaggcttagagaagttgagtgatttgctgagggctg48060 cacgggttggcatcccggcatgctctttcgctactttggctgcatctggttgcccacccg48120 ggcggatggggaatggactccagccagccaggagggcagagggctggagaggcagggccg48180 gaggttcagaccctccgctctgacgttgcgcctggtgaggccgggaggggtgccgcttgc48240 ctcttcagccctcacgctcttgtggaagtcgcggaattactgcaggcggaacttgcagca48300 ctgtgggcgtcttttccagagaaggacggagttgtggggcgggaggataaggcaaggccc48360 agccacttcgcatcttcgccccgccagctcctcgagatgggatataccagggttgctctc48420 caaccctctccgcaggagggactgatggaaacgcctgggaaagtagcccggtacccacaa48480 aggctgtctacaaacagagtcttactgtctttcccaggtctgtgccatagggattctcga48540 agagaacagcgttgtgtcccagtgcacatgctcgcatcgcttaccaggagtgcccgagac48600 cctaagatgttcggagtggttttttcgcacagacccgaatagcctgcccctcagccacgc48660 tctgtgcccttctgagaacaggctgatatgcccaagatagtcctgaatggtgtgaccgta48720 gacttccctttccagccctacaaatgccaacaggagtacatgaccaaggtcctggaatgt48780 ctgcagcaggtagagcacaggccccgaggaaaggactgcgggtgggtggagcttcagcca48840 ggacggggtgtgcttccctctcccggcccattccagccaggcccctccgggccagaggca48900 gcgtctgtcataaaaagggctggtgttccaggtggggtcagagagaggattgacaagtaa48960 aaacgatcgtcctttgaagggggccggcccctccacacctgtgggtatttctcatcaggc49020 gggacgagagactgagaaaatgaataagacacagagacaaagtatagagagaaaagtggg49080 cccaggggaccggcgctcagcatacagaggacctgcaccggcaccagtctctgagtttcc49140 tcagtattcattaattactattttcactatctcagcaagaggaatgcggcaggacagcaa49200 ggtgatagtggggagaaggtcagcaagaaaacgtgagcaaaggaatctgggtcacaaata49260 agttcaagggaaggtactatgcctggatgtgcacgtaggctagttttatgcttttctcca49320 cccaaacatctcggtggagtaaagagtaacagagcagcattgctgccaatatgtctcgcc49380 tcctgccacagggcggcttttctcctatctcagaattgaacaaatgtacaatcgggtttt49440 ataccgaaacattcagttcccaggggcaggcaggagacagtggccttcctctatctcgac49500 tgcaagaggctttcctcttttactaatcctcagcacagacccttcacgggtgttgggctg49560 ggggactgtcaggtctttcccatcccacgaggccatatttcagactatcacatggagaga49620 aaccttgggcaatacccggctttccagggcagaggtccctgcggctttccgcagtgcatc49680 gtgcccctggtttatcgagactggagaatggcgatgacttttaccaagcatactgcctgt49740 aaacatattgttaacaaggcatgttctgcacagctctagatcccttaaaccttgattcca49800 tacaacacatgtttctgtgagctcaaggctggggcaaagttacagattaacagcatctta49860 gggcaaagcaattgttcagggtacaggtcaaaatggagtgtgttatgtcttccctttcta49920 catagacacagtaacagtctgatctctcttttccctacagtccttgagggtgacagactt49980 aggagtgccttgggggcctctctgaggagcagctgatattcacgggtcaggaggaagcat50040 ttccattagaggggcagccggtggccagcctcacttggaaggtctttgaacctcgggggt50100 gcagggaggtggcagtggtgcaggttgccttctcctgggttccttgaggtgccctcttgt50160 acccggctcacacccttcccctccccgagtttcctgctcaggttcccgtctgagagcttg50220 tatgtaggacgtcagataggacagcataaatgtttggatccagaaacgcagaacagtttc50280 ctattttgagacttgacacctaattagtcatcttactatttaagctgaaaaatagtgtcg50340 tgttttgggtaacgttctgcaaatcgtttgctaatggcggctgagttgcttcacgccctt50400 tagggcaagagtgggacttgcctgtggacttctccgcggtcccacagggctctcgccacc50460 tggcagtggcctctgcatctgcaaagagctgcccgctggctgccgaagcttgtctcaggg50520 cagcttgtgtggcctcgcctcttcctggcttccccgtaacccttgctccgaactccgttc50580 agaaggtgaatggcatcctggagagccctacgggtacagggaagacgctgtgcctgctgt50640 gcaccacgctggcctggcgagaacacctccgagacggcatctctgcccgcaagattgccg50700 agagggcgcaaggagagcttttcccggatcgggccttgtcatcctggggcaacgctgctg50760 ctgctgctggagaccccataggtgaccctagttcccaggcctctcctggcctcctgtggg50820 gatggttggcaagggatggcgctgagggtggggtgggcccatggggactcctgccgtctc50880 tcaagcagaactcaaggagaattttttagctgctgtataatttctcgccatcgtgggtgt50940 aaacctagggttgggcttttttgctgaattagggcacggcagatgcccacttcacccatt51000 tttgataaaccagtatctggggtgtcagattcttggctgtctgcagggccgagttagccg51060 aatgccacctgcctttgatacgtgagaacgttgtctgagaaccgtgacttctgtgcttgc51120 ttgtgtctggtcagcttgctacacggacatcccaaagattatttacgcctccaggaccca51180 ctcgcaactcacacaggtcatcaacgagcttcggaacacctcctaccggtgggtcagacg51240 agtttacacctgtctcggggtcctcaagagaaccagcttggcatggtgctgagtccacag51300 ccccatgctgtgctgtggtggagggtggtggtctttctagacgctcccccgaagtgtgca51360 gagcgctggtgcccaggggtggggtgcggcctgggctgcctccaatgcccattacttgtg51420 aggaagcagctttgcatctgtgtgctgaccttgggcgggcgtcctgagctcctcgcaggt51480 gctgttgtagcagctgtgcagtaggtcagggctggcccccagtgcagctttgcacatgaa51540 gtaggaggaggccctgctgcttgtcagagcccagcagagtcttggtgttctgtcgggttc51600 ctgtggccggaccagtggcagggtgctgtggaagctgtcgaatctcctccctctgtccag51660 tacccccgctcgtcttctagctccctcctacgcccgggccacgtttcagttatgctcact51720 tcctctgaccgccgaggctcctgcgtgtctccatacagctcacgctgcagggccacgctg51780 tgggtgttggagacagctcctcctcgacccacggtgctctctcccaccaggcctaaggtg51840 tgtgtgctgggctcccgggagcagctgtgcatccatcctgaggtgaagaaacaagagagt51900 aaccatctacaggtaggctcctgggctcccgctccggctcagtgtccgacaggcgagtgc51960 tgctgggtgtccagagccccaggctgcgctcccgctgggctagggtttgaagttcactgg52020 gggactgcaggggaggacctggtgggggtggggactggcttcggtcctttcttggccgtg52080 cttcagctgcgcactctgcccttcctcccacagatccacttgtgccgtaagaaggtggca52140 agtcgctcctgtcatttctacaacaacgtagaaggtacaagcagctgggtgggaccaggg52200 tcgggttggagtgtgtgcagcctctcagggtggagctcagtggtgtcacagcctggttgt52260 gcttgcccggtggggcggccagtgcggccatgtacctgggccctgtcttctgactcgggg52320 ccacccatgttagacttctgtgtggaagagctcacacagtggtctgagacagccagccgg52380 caagactgcctctggctggtgcctggggccttggattttgggaaggctccctccatttcc52440 tgatgagagggtctccctgcacctaacctgctggtgcaaacagtaggggttttgctgaac52500 accggctttctcttcggggactttgttgcttgcccagcagcaggtgctccagtgaccggc52560 cctcataccatcttgggagggtgtcctggaagccgtgtctggcctcccgcgaccctgccc52620 cgtgtgtctttttcctgtgctgaccttgctgcggaaaattatggccctgagtgtgactcc52680 aggctgagtcctgtgggtccaacacgggatgccttggggcctcttctggagacgggatgt52740 gagtgacaggagccggccggggcagcttgccctgtgactgcacgtggccacagcctgtga52800 gggccgggggtgcttctccacccacgtggctgcccctcgggtatgtcaagggcttctggg52860 gctcatcacggggtcctagagacagtggcagggtgcacccccgttggctgcccttacagt52920 ttctgtgacctgagggtggcatctgtgcagtcggcgcggtctgtgcttctgtgggatcag52980 ggttccctctgtttcctgcctcagttggggctcaagcctcaggtgaggtggccccggagc53040 actcagaaggcatcggcggtcctgtgggctgctttctgcactcacgtttgctgagtgctc53100 agtgtgccaggactgaggaccctgaagctgctcttgtatttagggcggcgctcccctggc53160 agagactgagccaggtggtcccgcatgacccactaccaggcgtttctgggccctggccct53220 tggagggacagggtgggcggaacatgggcctgcagggaggctcccgcttactggaggcat53280 gtgctgtgttgctggagacatcctctgtgttgcttcttgttcgctgtggtttttggtctg53340 gtggcaccaaggaccctcagtcatcttgatgtgtggttgtccaggcctttttgttggtcc53400 taagaaggggctctgcctttgtgcccccaggttccctgacaggagctgccggctcgtccc53460 ggtgatgcctgcaggacgtgactctgggacggggggttgggcagatgtgctgatggaaat53520 tctcaagcaggcgtcatttccgaggtcctcacctggatttccaggacaggagtgcctgct53580 gggtgtccccagtcccatgcagcgggggtccttgggatagcatggaacgctgagcatggg53640 cctggccggccgtggtcctggacaagggcagtgccccggtggctgctgggcctgggacct53700 ggtggggacgctgggcctggtacctggtggggatgctgggcctgggacctggtggggagg53760 cctctgactgcctcctggtgctgcttccgtctgtgttaggcctctgggtattggggcccc53820 catctgtctcctcctccaggcctgtggactcagaccaggaagacacaggccagcccctgc53880 ctgtcccccttggcttgggctctcactgcccgacctggcgggaggttgcctagccgtgaa53940 ccttcgcaccctgtctgccaccggacaggctgtgagggggtgtctgcagcacctgcaccg54000 gcctgagcatcttcagagtgggctgcagctcctggaggggtctgagaggaagggaggcag54060 gtattttgggcgaatgaggagacagctggagagctggcacccttcctggcctgcgtcctg54120 tgaggactctggttggggacagcaagcttggggtcagcctggggcagagcctctgggacg54180 gccccgcccctcgtgccccttcccctcgcagctcctgtcctcgccccgccctcagctctc54240 cgccaggcaaggtttggcaagtgccgctgtgcggcagtgcctgctgattggctggtctgt54300 tgctatggtgctgcccaggggtgtgcttttcctcccctgccttccctgctatccctggga54360 gtatctggggttgggtcatcgctggtgtgtgtgagtgtgtgtgtgtgtgtatgtgcacgt54420 gtgcatatgtgtgcgcttctggcctctgcagctgagtcctggccctcggggggcctggca54480 cctcctggggacaggcacaaagcagccatgatggagtcgggagctgggggaggccccatt54540 gccccacgtggctgccctgtgactctggggtgcttgttagaagaggtatctggttctgtc54600 tgtgtttaagcaactccctaaggaattcttgtggttccagtttggggggcctgtactgta54660 gaggcaagggaggggcaggacatcccccagactctgacttctgaagccttttctgcccgg54720 ggcctctccgccagtacaggcagtgtcctttgccagggctgccatgctgcagaggggagt54780 gggccactgtttagcccaggaaaacctggctctcccttagctggaagttctgggcctgtt54840 gtggttggcagggaagctgagtgacggtgctaatcacaggggcacctgcaggggtttgtg54900 ggagatgcctctgtgggttggggcgataggctgaggggctgttcttccctgccctgagga54960 gggctgagtgtagccgccactcctgtcctgtcttgggctgtctcggagaggatgcgtaga55020 accctcgggatcctgctggcctccgtctggtccaccctgaacctcaggccttctgggggc55080 agaggaggattccctcaggatcactcgggtgggggcctctcttgggcacctgagaccctc55140 agtgggtgctttgtggcgcgttcacggttggtgggggacgcccagccctgcccgccgtgt55200 aggagccgttctgtcctgggcatccccctgtggtctgggacttagtggaccctgagggtg55260 tgtgtttacccctgcctcacacctgcagaaaaaagcctggagcaggagctggccagcccc55320 atcctggacattgaggacttggtcaagagcggaagcaagcacaggtgagacccctcagtg55380 aggccacgaccactgtccttccatggcccagctctcctgtgacctgtggaggcccggata55440 tatttcttcacttttctttgttcctttttaaattatgaaactaaccaccattcagtacga55500 aaaagtttaagcagctctgaggaagatagagtaaaaaattgtctccctcttccctggccc55560 tcagccatccccggtggccaccgtggagtgtggacggagccctgcaggcctgtgtctgtg55620 cggaagcacgcgcagttttgtctgcacagactgtcctgcagttggctgttttcactcagc55680 gttgtgggtatagcttcccatgctggtgctggcagctcggccttgttcttttgaggacag55740 cagatgtctcctatgtctacctcttacagcttcagagattcaagttataataaagctctt55800 cttatattgagggggaaacctccctcccccttttttttgaaacagggtctcgctctgcta55860 cccaggctgcagtgcagtgtcacagtcttggctcactgcagcctcagcctcccaggctca55920 agcgattttcccacctcagcctcccaagtagccgggactgcaggcacgcaccaccatgcc55980 tggttaatttttgtattttttgtacagacagggtctcactctgttgctcaggccagtctc56040 ctgagctcgagagttccacctgccttggcctcccaaagtgctgggattacaggcgtgaga56100 ccccatgcctggccagctctttttttttttttttttttttttgagacggagtctcgctct56160 gtcgcccaggctggagtgcagtggtgcgatctcggctcactgcaagctccgcctcccgag56220 ttcacgccattctcctgcctcagcctcccgagtagctgggactacaggtgcccgccacca56280 cgtctggctaattttctgtatttttagtagagacggggtttcaccgtgttagccaggatg56340 gtctcgatcttctgaccttgtgatccgcccacctcggcctcccaaagtgctgggattaca56400 ggagtgagccaccgcgcccggcccagctctgctttttcttagtggttctgcgttgtgttt56460 gtttctatccaggaatagggttggttttacttttccatcgagtttttaaagagacgacga56520 tttacatggtcggaaactcacgaggactccccatcccttggtcggaaactcacatggact56580 ccccatcccttggtcagaaactcacgtggactcccatccatcccaggcagcagcttccca56640 cctgggccctacgtgcaggatgagggctccttccgggtcagaagacatggcggcctcggg56700 gcaccgtcccctgcatggggtgctcacaggatcttctcctctctccttcccagggtgtgc56760 ccttactacctgtcccggaacctgaagcagcaagccgacatcatattcatgccgtacaat56820 tacttgttggatgccaaggtgggggctcagtcctgtagctgacgactcctgatgtccagg56880 ggtgtccctgggcttgggaacagctgtccgagcctttgctgcttcagggccttagatcag56940 caggcctgggtgggaggactcacctctgtcactgggcaggggctcaacctggccagacac57000 acttgtgagcagccccaggccacaggtcagttttctgagcagtctgggagcgggcaggct57060 ggtgggagtgaggagagacctccaggctgtggtccataggccagtgcccgctcttgatcc57120 tgacagctcaggttctctccttcacgtcaggccatgggaggcaccgagaacacaggaagc57180 ccactgactcccctcttcccagcgcgtgcccggccccacactcactccccctcccagcat57240 gtgcccggcttcacactcactcccctcttcccagtgcatgcccggccccacactcactcc57300 ccccacagcatgtgcccggcctgacactcactcccctcctcccagtgtgtgcccagcccc57360 actcccttccgccccgtgtgcccagccccacgctcactccccccgccagcatgtgcccgg57420 ccccacactcaactcccctcctcccagtgtgtgcccggccctgctgccctcctccccatg57480 tgccctgcttttgtgccccacactttttacttagtgcaggtgggatcacacgccacgggt57540 caatggtttgtgtgttcacgtgacgatggcgtggtgacgtttccagatcccgtcgttggt57600 tcgctcattctcggggtgtatatttattgagagctcatcatgctgggtgctattccaggc57660 atagcaagactggcttcactcacatggagctttgattctagtggtggggacaggtggaca57720 gcaaaagagtaagcacgtgagctgacgatactgaagggaaatagagcagagggaggaggc57780 ggagaccgagccaagcgggcccaagtgcgatgtcggcgggaggtggggaatgctggtggg57840 tctgaggggagcctcagcaggtgcagcagagcaagggaagaggtgagtgggggcggctgg57900 ggggccgactcctgggaagctgtagcagaaccccacagagagctggtgaggtttgccgtg57960 gttgtgggtgactcggtgctttgagccctggctgcccctgggaaccatctggagagcttc58020 taacccaaccaggcccctccctgggacagttatatcacagctggtaagccgagtctaaca58080 ctttcacggaaacgcagaagatctaaaacagcaagatgaccgtgaagaagaacagagctg58140 gaggactcacctcgctggtttcaagactcctctaaagctgcaggagtggaggtggagatg58200 gcccagctcaggcacaggcctgcaggccatggagaaggcagcaagctcaagctgacccac58260 acgcatgtggtcattgttttttttttcagttggaatctcactctgtcacccaggttggag58320 tgcagtggcaccatctcggctcactgcagcccccgcccctaggttctagcgattctccca58380 catcagcctcccgagtagctgggattacaggcgtgcgccaccatgcctggcccttggtga58440 ttgttttttgacaaacatgccaatttaattgagagaggaaatgaaggttgatttctggtt58500 ttctgaaaaaatggtgctaagaacagctggatatctgttcggaaaacagtgaatcttaac58560 tcttgttttaccctgtataaacctaaatgtaaaagctaaactaaaagttatagaaaggaa58620 catgggggaggtctttgcaactttggggtaggcagagatttcttagtatggatacacaag58680 gcactagccatgaagaaaaacattaaaatttagacttcaccaaaatttaaagcttcaact58740 ctgtggaagagttgagaaaatgaaaaagcagttaaagaaagggagaaaatacttctttca58800 aaggacttaaaaaattttttcagccctcctctgatttgaaaggacctttgaccagagtat58860 gtaaaattctcccataactaagcaaacaacccacttaaccactgggaagggatctggaca58920 gacgtttcaccaagatgggtggaatggccagttaaccactgggagagcatccggacagac58980 gtttcgccaagatgggtggaatggccagttaaccactgggagagcatccggacagacgtt59040 tcgccaagatgggtggaatggccagttaaccactgggagagcatccggacagacgtttcg59100 ccaagatgggtggaatggccagttaaccactgggagagcatccggacagacgtttcgcca59160 agatgggtggaatggccagttaaccactgggagagcatccggacagacgtttcgccaaga59220 tgggtggaatggccagttaaccactgggagagcatccggacagacgtttcgccaagatgg59280 gtggaatggccagttaaccactgggagagcatccggacagacgtttcgccaagatgggtg59340 gaatggccagttaaccactgggagagcatccggacagacgtttcgccaagatgggtggaa59400 tggccagttaaccactgggagagcatccggacagacgtttcgccaagatgggtggaatgg59460 ccagttaaccactgggagagcatccggacagacgtttcgccaagatgggtggaatggcca59520 gttaaccactgggagagcatccggacagacgtttcaccaaggtggatggaatgaccagtt59580 gagcacatggaaagtcgcccagcatctccagtcataggagaaggcagattaaagccacgg59640 ggagccgacactgtggtcccactggcatggctgaaattcagaagccctgagtgtggcatg59700 aggatgtggaacagctggatctcatccatcgctgtgaagttgtgtagccactccacaaac59760 gtgtggcaaacagccgagccgggagaagggaagacgtgttcaaagattcatatgtggcca59820 ggctcagtggctcacgcctgtaatcccagaactttaggggccaaggctgggggatcgctt59880 aagcccaggagtttgagaccagcctaggcaacatagggagaccccatctcaaaaaaaaaa59940 aaaaagaaaaaagaaaagacttcagtgtgcaggtttaccagagttttgtttgcagttgcc60000 aaaactgggaagcagcccgcgtgagcccatccacaggtgaatggacagaccgtggtaccc60060 gaacactaacagcagccacgggcgtggactgtggtcacacagcagcagggagccgatgag60120 tctcggacatgctaacccagagaggcccattgaggaggacctactgttttttgtgttttt60180 gttttttgttttgaaatggagtctcgctctgtggtgcaggctggagtgcagtggtgtggt60240 cttggctcactgcagcttccgcctcttgggttcaaacagttctcctgcctcagccttccg60300 agtagctgggactacaggcacccgccaccacacccggctaatttttgtattttcagtaga60360 gacggcagttcgccatgttggccaggctggtcccaaactcctgaccttgtcatccactca60420 ctttggcctcccaaagtgctgaggttgcaggcatgaaccaccgcacccggctggacctac60480 tgttttattccatttatgtgacactctattaatagaaaaggcaggggtggggctggtggt60540 tatatggtgcacataactgccagaactcagtacacttaaaatgaacatcttaatgtgtga60600 aatttttttttttgagacggggtcttgctctgtcacccaggctagagtgcagtggtgcga60660 tctccactcactgcaagctctgcctcctgggttcacgccattctcctgcctcagcctccc60720 gagtagctgggactacaggcgcccgccaccacgcctggctaattttttttttttttttgt60780 atttttagtagagacggggtttcacagtgttcgccaggctggtctcgatctcctgacctc60840 gtgatccgcctgcctcggcctccgaaagtgctgggcttgcaggcgtgagccaccatgccc60900 ggccaatgtgtgaaaatttaaaagtaccaaagctggaccccaccccagattgctcccatg60960 acactctgtgggtgggacctgggagttgggttttgttttgttttgttttgtttttgagat61020 gaagtctcactctgtcgcctaggctggagtgcagtgacacaatctcggctcacattaacc61080 tctgcctcccagatgaaagcgattctcctgcctcagccttctgagtagctgggattacag61140 gcacacaccaccaccccctgctaatttttgtatttttagtagagacggggttttaccatg61200 ttggccaggctggtcttgaactcctgacctcgtgatccgcccgcctcggcctcccaaagt61260 gctgggattacaggcgtgagccaccgcgcctggctgggagttgggtttgtaaatctccct61320 gagtggggctggggcagggaactgctgggtctgggtcttcctggctcctctggtctgtgg61380 cttcctgactgcggtggccgggggctcccagggcatcgtggccgtctgtcttgctgagcg61440 tggcacgtgcctttccatgctgtggaggagcgtctcccggtatggcgaactgctggttag61500 ggtggggcggtgttgccaggtcatccaggtctggcctctgctctcgacatcgccggcgct61560 gttgctcatctgcgcttgtgatgttcgatgcctgctgcacatgtcttggcttccctcttt61620 cccggcctctgtgagctccagcgctgcgtcccttctcttcctcctgtagagccgcagagc61680 acacaacattgacctgaaggggacagtcgtgatctttgacgaagctcacaacgtggtgag61740 tctccgctggcctcctaaacacctcctattgcttctggcctttttgtcaagagccacgca61800 aacctttctggaggggctctggccaaactcctgaagccctaggtgcccaggactggggac61860 tgagcacaccaggagcttctgccaccccctcccgccctgatccgatgcctctgctggggc61920 tggagactggccagctgggccagggacctgcccgtcaggcgcagggcccccacaggccgc61980 tcaccagaccctttccctccagccagctcggggtcagcctgggccagggctgtctcctct62040 gccctcggcagcagcaggcttgtggtcttgcctgcagtgtctctgcccttccggccacat62100 ggcttgagactgaggcaggagaatcgcttgaaccttggaggcagaggctgcagtgagcca62160 ggatcacaccactgcattccagcctgggtgacaaagcgggattctgtgtcaaaaaaaaaa62220 atgttgactgggcgcgctagctcatgcctataatcccagcactttgggaggctgaggtgg62280 gcggatcacgaggtcaagagatcaagaccatcctggccaacatagtgaaacaccgtctct62340 actaaaaatacaaaaaaattagctgggcgtggtggcgtgtgcctatagtcccagctactc62400 aggaggctgaggcaggagaatcactcgaacccaggaggtagaggttgcaatgagccaaga62460 tcacaccactgtactccagcctggtgacagagcaagactccgtctcaaaaaaaataaaat62520 caaaaagaataattggcaattccagtgaaataattgtttgtttgtttgttgagacagggt62580 ctccttctgtcgtccaggctggagttcagtggtatgatcttggcccactgcaacctccac62640 ctcctgggctcaagccatcctcccacctcagcctcccgagtagccgggactacaggtgca62700 caccaccacgcccggctaatttttgtattttttgtagaggcggggtttcccagcgttgcc62760 caggctggtcttgaacccctgagctcaagtgatctgcccaccttggcctcccaaagtgct62820 gggattacaggtgtgagccaccgcgcccggcctgaaacaatcgtttctaaatattggtgt62880 gggccacacagtcatgtttggacctacttgtggccttttacagaccccaggccaaggctt62940 tgggaacttggctgtcagcctcctgtgccttctgcacccccaccccatttctgctttctg63000 gaacccccgatcctgtcctgttctgtggtgattcgggtgtgcttgggctctaggagaaga63060 tgtgtgaagaatcggcatcctttgacctgactccccatgacctggcttcaggactggacg63120 tcatagaccaggtgctggaggagcagaccaaggcagcgcagcagggtgagccccacccgg63180 agttcagcgcggactcccccagcccaggtgcgttcatagccagactgcttggtcctgagg63240 cctgcgctgctgcagggtgagccccacccggagttcagcacggactcccccagcccaggt63300 gcgttcatagccaggctgcttggtcctgaggcccgtgctactgcagtgggcagcctgccc63360 tgtggctgtgtgtggtcggcctgggcaccatctattcaggctggcactgcagggcatccg63420 cttctctcagaggcttcttgggtgtgaattcttcagggtcctgtagcctgtggaagggct63480 ggtattgttcagtagttctggtattttccaaagacctatgtcttctcccagccagtatca63540 acttggcctctactgtgtaaaactggaaaactctactttgtgaagctgagttgggagcat63600 cgcttgaggccaggagtttgagaccagcctgggcaacatggcggaacctcgcccctgcca63660 aaaaattagccaggtgtggtggtgtgctcctgtggtccaagcttttctggaggccgaagt63720 gggaggcgtgcttgagcctgggaggcagagcttccggtgccccagatgactccactgcac63780 tccagcctgggcggcagagtgaggccatctcaaaaaaaaaaaaaaggaaaactaaatata63840 ttcactgtaagggcattttgcatctttaaatgacccacaaatctggcatgcatcagctgc63900 tctgcctgtaggttccttcccagtgtttgtccagaggtgtatttccacacagcgctagtc63960 acggcatatgtggaaaacgtggaaacccttcatggatgttgtcagttggtctatattttc64020 tttcttttttttttttttgagatggagtttcacttttgttgcccaggctggagtgcaatg64080 gcgcgatcttggctcactgcaacctccgcctcctgggttcaagcaattctcctgcctcag64140 cctcccaagtagctgggatcacaggcgtgcaccaccacgcccagctaattttgtattttt64200 agtagagatggtttctccgtgttggccaggctggtctcgaactcctgacctcacgtgatc64260 cacccgcttcggcctcccaaagtgctgggattacaggcgtgagccgccacgcccggcctt64320 tgtccatattttctacatggcttctgtaaacagctgactaggagtctgtgtgaatatctt64380 cataggttctgctgtgacactacttgctcgtgagcatctccaggtgtaaacagcatcagc64440 ttcccccattttcctttaaaatcgcacatgtggacggacaccacggggaccctggaccct64500 ggggagccccgtcctcacccttctcaccaggatggctgcttggtagagagtgagtttgca64560 aagttggcatttgtttagtacagaagttatcaggtgttctggctttagaatccctttata64620 tatatatatatatacatatatttaagtgacagggtctcactctgttgcccaggctggaat64680 gtggtggtacaatcaaagttccctgtagcctcggcctcctgggctcatgggatcttcccg64740 tctcagcgtcttaaagcgccgggaccacaggtgtgcaccactgccaccggctctcaagat64800 tgccacgcagggagttgcagtgggggaaggggttcctgggactttgaacgctccacctcc64860 ctcctctccacagtcccccaaccccacctctctaacggggtggacggccgcctctttcca64920 tccttcgcttggcgcagggtggggagagtgacaggtctccttccctcatctcggcagctg64980 ccatttcatcgcttacataacgtgggagaaacatccacccacccccaggcctgtgtgaac65040 atcaccacggggccttctccactcttcagttttgttagttacttgatgtgcagggctttt65100 tgttgtaactagtgggggacgtgtggtggggtgggcttctgccatctcattcaggaccag65160 aacttcagttttcatccctatctgttcccccacccctttggagatggggtctcactctgt65220 cacccaggctggagagcggtggtgccatcacggctcactgcagcctccacctcctgcagc65280 ctccacctcttgggctcaagtgatcctcctgcctcggcctcccaagctcctgggactaca65340 ggcgtgtgccactgtgcttggcagggtccattcttttcctcacactttatttattgaaga65400 gcccaggccgtttaccctgcagagtcggaatctgtacaggaggggcagccacacgagttc65460 cccggtttactctgaacttaggtggcttgagggccccagttagactgcggccaccgtttg65520 ccgggctccagatgggacgtcctttctatcagaaggctcaCagtatctcctttcccgttt65580 cttcccatgtgaacattgttgctgctgaacacctgaatatgttaatcactgggggcttgc65640 aagatggcagtgtgctaattccatcatctagtcagttagcaggaataacttaggaccacg65700 ccctgcaccatatcagctatgtggtgatcccattcacacaggaaaggtgggacaaatgct65760 gggggtgggccgggtgtgctgtctcacacctgtcatcccagcactttgggaggcccaggc65820 aggcggatcacgaggtcagagattgagaccatcctggccaacacggtgaaaccccgtctc65880 tactaaaaatacaaaaaaattagccaggtgtggtggtgcatgcttgtaatcccagctact65940 tgggaggctgaggcaggagaatcacttgaacccaggaggcggaggttgcagtgagccgag66000 atcgcaccattgcactccagcctggcaacagagcgagactccgtctcaaaaatcaatcag66060 tcaatcaagtgtcatcactgaatgtttgtgtgtgaacgtggggattggtcctgccccatg66120 ctccctcctgaatctcactcctgacctcagttgctgcaccttgaggtgttttctgtgggc66180 tcttgtgtcctgaccccggcggttgtggcctctgctgtctgggagtcaggatttttcaca66240 ctcatgtcctgctccagacctggaatcagccaagtctccaagaagccctgctttcttttc66300 ctgcaagacggtatttcaagacccgccgtgcggcagcgggttggtcatggttactgggtt66360 ggtcgttgtgactgggtgttttcgtggagatacagccatacgcacaggtgtgttcacaaa66420 tgttaattctaaaggtcaaacacccggccaggcataagggctcagcggtaatcccagcac66480 tttgggagaccaagactggtggatcacctgaggtcaggagtttaagaccagcctgagcaa66540 cagggtgaaaccccatctctactaaaaatgcgaaaattagccgggcatggtggcgcacac66600 ctatagtcccagctagtcgggagacagacacgagaattgcttgaacctgggacatggagg66660 ttgcagtgagcagagatggcgctgctgcacccctgcctgggtgacagagtgacaccctgt66720 ctcaaaaatgaatagataaataaagataaaacacctgctcctcttggtgtctccagtttg66780 gatttggcctgtgtagcctcttccttcgcctgttggtggatttggcctgcacggattctg66840 tgtggcctcttccttcccctgttggtggatttggcctgcacggattctgtgtggcctctt66900 ccttcccctgttggtggatttggcctgcacggattctgtgtggcctcttccttcccctgt66960 tggtggatttggcctgcacggattctgtgtggcctcttccttcccctgttggtggatttg67020 gcctgcacggattctgtgtggcctcttccttcccctgttggtggatttggcctgcacgga67080 ttctgtgtggcctcttccttcccatgttggtggatttggcctgcatggattctgtgtggc67140 ctcttcctttccatgttggtgtccttttttccatgccaggaatcctggttctcaagggcg67200 gggttgttggcacgagcgtgatgcagactgcctttgctgcctttctcttgcccagggctg67260 aacatggagctggaagacattgcaaagctgaagagtaagtgttgccctccccgcctcctt67320 gcagctgggtggggcctcctccttgcgaggaggtgggtgacacctcctcgacccacagtg67380 atcctgctgcgcctggagggggccatcgatgctgttgagctgcctggagacgacagcggt67440 gtcaccaagccagggaggtgagaggcggggagccagccccttcactgcaggcccagccta67500 gagctagaaacgggccatggtgcagtcctgggctgtcacatcacgagtgaggcctgtttt67560 caggcctgttttccctttttgagacctgggaggagcacctgctttgcatgatctggttgc67620 tgagatgttgagaggagcagcacacactcccacgggacagcacacagccccccacggaac67680 ggcacacacacccatggaacagcacacacactcccacgaacagcacacacactcccacga67740 acagcacacacactcccacggaacagcacacacacccacggaacggcacacacacccacg67800 gaacagcacacacactcccacggaacagcacacacacccacggaacggcacacactccca67860 cggaacagcacactctcccacggaacagcacactctcccacggaacagcacacacactcc67920 cacggaacagcacacacacccacggaacggcacacactcccacggaacagcagactctcc67980 cacggaacagcacacacactcccacagacagcacacacacacccacggaacagcacactc68040 tcccacgcggggccgctgggtttcctgcagtttctcctcctccaggcctttccctggacc68100 ctggtccagtccgtcatttgagcacaggtgcctgttagaacgagaccttcttgttaggac68160 gatgagtgtcccagccaccacctcttttggactccgggaggcctggaacgttctgaacgc68220 tccgtggggctccagtcttctccgcagccagggcagcagggtttgctgtctgtcctgcag68280 gcagatgaggagtcagggctggggcctgtgtgggggctctcctgagcgcgcagccgccga68340 ggtggagcgtgttctgcctgagcgccgacctggtcgggggaatcccagttgcttccaggt68400 ggagccactgtcctcagcgtaatgctcaaggctctggcctggctcctcggccaccctgca68460 ccctcagggtcccctcctgtagcttctgctgccccatcactgtcactctccaaagctttg68520 gggactctgcccagagccaccgcctcccagaagcccctgacaacctcttgacgaccccct68580 agtgaccccatccctcccctctgacggcggcccctgctctgaggcggcttcttttcctcg68640 gtgctgttctcgtgctggccaggcctcctctccccacctggaggctcctgagggcggagg68700 cctctcacctccaatgctggcgtcccctggagggctgaatttgtttccgagggaaggaaa68760 cttccacagttgttgccttcagttccaaagctgcagcctgatttccccctccaggctcga68820 gcctgttttcttctcggcagctacatctttgaccagtgtcgtcccccctcaggcccgagc68880 ctgccttcttctcctcagttcccaaagctgcagtctggtccccccgccaggctcgagcct68940 gccttcttctcctcggcagctacatctttgagctgtttgctgaagcccagatcacgtttc69000 agaccaagggctgcatcctggactcgctggaccagatcatccagcacctggcaggacgtg69060 agtgctggcacggggtctttggtgcgggcaaatgtggcgtagggggtgcagcaggcctcc69120 atcttggcagtcagggctcccctggccgtcacctggccgtcagcaggaacaggcccacag69180 aacctcatcttctgatcggggcgtggaggcgttagtgccacttgccagctgccgtagagc69240 ctgtcccagttctgcagctggcggcttcgtcctacagcctcatcccattattctgctttt69300 gagaaagagcagcccaaggccctagctggcttgtggggcctctggcttctccacaccacc69360 ccgagttctgcttctcagagttgtggggtccagaggctttgcccagaggcggtgtcccca69420 tgggctgctctggtttgagacgccgggcccagcggggtctctcctctgctgcgctcccgg69480 gtgctggggagggtggcttttgctgcttcaacccttaggcgaccatagagcctcttttca69540 agtcccactgacccccttggagactctgtccctgcctggcttctctcctggctgctggga69600 agagcaggcgaactgcccgccctgaatggatgctgcgctccaccctgggccccccattgg69660 gcaggagatggagcttggcagtcgggctgagcgggctcatgctggaagggccggggctgg69720 ggtcggggcctcccctgcctgcagtgtgggtgtcagcgccctgctgccctccaggtgctg69780 gagtgttcaccaacacggccggactgcagaagctggcggacattatccaggtggggcctg69840 ctcctctgtggcatctccttccctgatggaagccgggcgggtgccttctcctgctgtatt69900 agttaactgattctagacttggggatgggagaaaggcccctacaccacctgtttctgatt69960 ggcaaactctcggctcctttccagtgccctaaacccacactgggcctcctgcagggatgg70020 gggaggacgaggtctggtggcacatgcccagggtgatgctggtgagggaggacgcaaagg70080 acagtgggggccggggagccgctcctgccctgtccgggccctcaggccaggggggaccca70140 ctgctggcagccccagcagccccagctgcacgcagatgaagagctctggacacacgcggc70200 ttcctgaacagcttctccagggacagacaaatggggaccctgcaggttcccggcaggggt70260 gtccctgggagcccatgattgggggtgcgaccctggcccccttctcattggccccgtcct70320 gtcctgcaatgcccgtcccatgtgaggtctgcttctggctccatgcctatggcagcacct70380 gctttccctggcgtagaggtgcttgtccggtttgtggagggcacgccccattttgggtgc70440 tctgggcacgttgcctctccggggcctcggtggcttttttagaagcagactcagaagtcc70500 ctgactggggaagccaaggcacaggtggctgtgtggagccctgtgaggcctcctctgtgc70560 tgcccacgctgtacctgctggccacacgagatcatggcagggttaggcagggctgcccag70620 cgctatgacagcttcatgagtgtccatctggcctgtggggtgcttgagctgggggaggcc70680 gcagaagaaccctgggatgcatggctggcctgtgcatgctgctgggcatggagctgcaga70740 tcccggaacaagcaggcactgccttctccttcacagacgcagctctgagcgggggcgaga70800 cctgggcagggaccaggtggggtgggcacagggtggtggggcccaggctcagccctccct70860 ccactgtggccgtctctgtggccagtgacgccacagcctgtgtcttctctgtgcggtagc70920 tggggctggaaggacagcactgccttgtcctcccaactcctccccaaaggcacggtgggc70980 atcccaggcccagacccctctgtctgtggctcctgcctgccaagggctgctgtgctgtcc71040 cgcatggagtgtggttggctcttcaagcaggaggccgtgcacctatcaggcggacctgct71100 tccatgtccctgatgggtcactgcaaagcacctccagcacatggccaggcgaggtagccc71160 tgcagcccagggcctggagggcaggtgtgagctggcccgggcctgtccctccctggaata71220 cagcttcccaggctcccacttatggagaagtctcctccacactatggaactgaatcctag71280 aatgtggcttctgaggttcctacactcgaactgaatcctggaatgcggcttccaaggctt71340 ccagctatggagaagactccacactctggaaccgaatcctggaacgcggcctcccaggcc71400 cccagctatggagaagactccacactctggaaccgaatcctggaacgcggcctcccaggc71460 ccccagctatggagaagactccacactctggaaccggatcctggaacgcggcctcccagc71520 ctcccacttaaggagaagtctccacactctggaaccggatcctggaacgtggcctcccag71580 gcccccacttaaggagaagactccacactctggaaccgaatcctgcacactccatcggtt71640 tggaatttcctttggctgctgctctaagtagccgctggtggatgactcagcttctgccag71700 ccctcgggtgcctggaggatgagggactgcacacagtgctcacccgcgttggctcctgag71760 cccctgcaggtgtgggcggtgcccatagggctggtgctgggttgggcctgcagccctgag71820 tcacaggtgaccctgggggcagagtggggccagtggccccaggaagaggatgtgggatgc71880 acagctcagctggaggcgaactccaggcagggtcaggccgtgtgctcggaagtcagggct71940 tagctggaggcaaactctgggcagtgctggcccgtgttggggaaccagttgcccctgggc72000 ccccgtgagactgctgggtcctcatccctctctgcctgaggccggagctgccctgggctg72060 aggcacagggggatttgtggtggtgtttttttgagaaagggtctcgctttgtcaccccgg72120 Ctggagtgcaggggcttgatcacagctcactgcagcctcaacctcctgggcccaagtgat72180 cctcttgcctcagccacccgaggagctgtgaacacaggtgtgcaccaccgcactcagcta72240 atttttaaaatttttttgtagagatgaggtcttgccatgtttcccaggctggtctcaaac72300 tcctgggctcaggcagtctgcccgccttggcctcccaaagtgctgggattacaggcaaga72360 gcttccatgcctgcccagcagaaggcttttcgaaggaagctgtttcctgaggcagactca72420 gccctgctcatggcagccaccagcgtgggggtgaacttgttctgttacttccatccccgt72480 gggccaaatgctttggtaaaacacaaggccctgtgtttagctgtcttgacagtgaaaatg72540 gctgggaaggaaggaaggaacggaaggaaatttctctctccttctgtgcgtacccaggca72600 cgtgcacatgcatgcagagtacgcacacacgcacgcacgcctgcacaaatccacgcatgt72660 tgccaagtctctgtgttccagccgtggtgtctgccccccggtgttctctagttcggcttc72720 tccgcatttctgtgaatgattccggcttcttggtgttcccagcagaactccctcaagtct72780 gcggcggggctctgacggcggtggcttggctgacatggccacattgctgagcctgttggg72840 ggctttgcgttcctgttctggccgtttttggctcgttttccaggaacggtcgtcacgcgc72900 tcctctcctagtgcaggcatcattcctttcccattgatttgcagggttctctgtaagttc72960 tgaggatcccatatacatatactctctgtaagttctgaggatcccatatacatattctct73020 ctctaagttctgaggatcccatatacatattctctctctaagttctgaggatcccatgcc73080 gacatacatattctttccttgtctcatgctggtcattttttccattttcatgacaggttt73140 ggtgaacacatgtttccttgtcagatttttgttctgagcttgtgcctcccgaccaagatg73200 ctaaaccgggtcttgtgtattctccaaactgcactgtagagtgacggagctttgtgtctg73260 ggcctccatgccttctgacgtcacctgtgggggtgtgaaaggcagactctaccttgattt73320 ttcccagcacgccacaccggtggttctgtgcgctgaccgagcggctcggcttcccccaac73380 tccactgggcacctgccacacttttcctcatgtttttgttcactgtggttttgtcgtaag73440 tcctggtgttggcctgaaccaatttctttttgtttgtttttgagacagagttttgctctt73500 gttgcccaggctggagtgcagtggcgcgatctcggctcactgcaagctccgcctcccggg73560 ttcacgccattctcctgcctcagcctcccaaatacctgggattataggcacctgccacca73620 cgcctggctaattttttgtatttttagtagagacgaggtttcaccgtgttagccaggatg73680 gtctcgatctcctgacctcgtgatccgcctcccaaagtgctgggattacaggcatgagcc73740 accgtgcccagcctgatatttttagtagaaatggggttttgccatgttggccaggctggt73800 ctcgaactcctgacctcaggtgatcctctcaccttggcctcccagagtgctgggattacg73860 ggtgtgagccaccacgcccggcctcttgttcttttgaaacctgccctgacgttttttcca73920 tagtgcatcttggagtcagcgtgtctacttcctgtaaaaatcttactgtgattttgacta73980 gaatgtgttgaattcctgttttttttttgagtcagggtctctctgttgcccaggctggag74040 tgcagtgggaccatcacagctcactgcagcctcaacctcctgggctcaggggatcctctc74100 agctcaacctcccaagtagctgggaccacaggcacatgccaccatgcccggctaggtttt74160 tttttttttttttttggtgaacaccctggggttgcaccatgttgcccaggctggtctcga74220 actcctgggttcgggcagtttgctcctctcagcctcccggagtgctgggattacaggcct74280 gagccactgcactaggccatgttgaatttctagattaatttggggccctcaggggcacag74340 agaggagggctgggccagttggcgggaggagaggcccctcgggctgccgcattttcagtg74400 catggagatggcctatgttgggggaacacagagctcaccgggggtccctgcagggaggag74460 aaagggtcaggcaggtgccagctcctgtccattggcctggggctgcatgatggcaggggc74520 cggtgaaccgatgacccctgggtgtcctgtgaccttctgtgtatgcggctgatgctgcag74580 aaagtcgggtggcctcaggctcctgacggggctgcacttcctctgcctttcagattgtgt74640 tcagtgtggacccctccgagggcagccctggttccccagcagggctgggggccttacagt74700 cctataaggtaggggccacctccaggaggcaggtggagggcagcccttgttccccggcag74760 ggctgggggccttacagtcctataaggtgggggccacctccaggaggcaggtggggctgg74820 gggtcttctggtcctaaaaggtaaggggctgcccccaggacatgggcggggcctccacac74880 tcctggtcctgtcccctccaggtgcacatccatcctgatgctggtcaccggaggacggct74940 cagcggtctgatgcctggagcaccactgcagccagaaagcgaggtacagacctgggccca75000 cacgctccccgcccgcccgggtgcagtgcccggcaccaccatgccacaggctaggcacat75060 gcccagccgtggatctcctgcccccatgggcctggccaccttctccatatccaggccaat75120 ccagagcattctcctcactgtccctctgaagattggagttactgagagacgtaggagatg75180 gcctgatggcaccgtgacctgcccagagtcacctggttggtggtggcagagccacagccc75240 agccaggcctccctgctgggacacgctcgtttatgccgaggccgtcagcacagagcctcc75300 acagtgaggcacggctctgcctgctgcctccacgcagcgcctggccgggccaagcctcag75360 ggtcacatctgaagggggcccggctggccctgttgtccgaagcccctggtgcgctcagcc75420 ccgaggccccacgtgccttcttggcttcctgtgctccgtggcgtcttcgagtcggtgctg75480 ccggggacgctgtgtggatggggtctgtgagtgtgccctcggctccgtgtccggagccct75540 gtggttcttggggtgtatctggccccacccccactgcgtggtgtccagggtggggcttca75600 cggctgcagctgcgggagctgctgcccctgccttgtgctccagtggggccttgcctctgg75660 gcttggttcgtccctctctggaacattctttctcagctgctgtccgacccatggtggcat75720 gacgtggccctggctgaagcagcccttgtgcggttgctgtggttgggtctgcctggccga75780 gccggaagggaagggctgggagggcgtcagggtggcgtggcttgacccccgctcggtgat75840 ggtcctgcagcaaggcctctcccagcaggaagcgtccatcccggggggaggccggcgccc75900 ctcacgcagttggggttgcgggaggcagtgcgtgcctgaggcagccggtgcacagattcc75960 aagggcctggaatctgtttgttccattgacctctgatgtcacttgacttctcagaagcag76020 ccactccctgcactgggcgtttgtaggaaatgagctcctggaggagggggtggggaagtt76080 cccccattgcagggcacactcagccccaggaaggaaacgtgcctcgtccctgctgactcc76140 gaatcgcagtcagagtcgttctgcttgtgccgtgttgaattcccggcatccggcatccag76200 actcagcctcctccccaggccacggccgccgtggccagtcggtcaagcccttctaggaac76260 ttcctttgagctggcgcccttgttcactgctgacgccactcagaggcttgtgcacgtgtc76320 ctgcttccaggcagagctgggaactcgcaccccgtcttctgcacgcggccgtggaatgtc76380 gggatgccggcgcttccttcccgtgtgctcttggcggggtgggcttcttgccctgagccg76440 catgtcacagtttctgcagaagtttagggttggagtgggctgacctctctgcaggtgtcc76500 ccagcctctgcctggggtctgcctcctactcccaggaccccctgtcccccagaggggccc76560 caagctggcaggctcacactcagggcagcctcctttgttctgacttctgcacagtgggcc76620 tgggtggctgcccgcggctcgcttgcttgatgccagtgggtggagagggtgatgggcaga76680 gaggcaggtggtcaggcccccagtcccgtcctcacactctgtgccctctgccgccccccg76740 ccccacagggaaggtgctgagctactggtgcttcagtcccggccacagcatgcacgagct76800 ggtccgccagggcgtccgctccctcatccttaccagcggcacgctggccccggtgtcctc76860 ctttgctctggagatgcagatgtacgggccacccctgccagggcctgagcaccggtgaca76920 cctctgacatcagcggggtggaagtggtgggggtccccatgagccgggtgctgggggtct76980 cgggcctcgagggctaaaggggtgctggtgcacttccccactgtctgctccctctggcca77040 cgctcagccctttcccagtctgcctggagaacccacacatcatcgacaagcaccagatct77100 gggtgggggtcgtccccagaggccccgatggagcccagttgagctccgcgtttgacagac77160 ggtgagggcctgtccctgggccctgctggggtgggaggtgggggagcactgaggcctgag77220 gccctgagcagtggcctctccggctctaggttttccgaggagtgcttatcctccctgggg77280 aaggctctgggtgagtgccctgaatgccccagctgtgcgcatcctggatcctggacccct77340 gctcccaagagctggtagggacccctgcagacatcctgcccctgccttgaccccggcccc77400 tgcacttccaggcaacatcgcccgcgtggtgccctatgggctcctgatcttcttcccttc77460 ctatcctgtcatggagaagagcctggagttctggcgggtgcgtctcccctgtgttctggg77520 cggggtgggtgagggcagggctggagcatgaagcaggcagtggtcacagctcctgcttgc77580 cctcatcggatcggcggcgtgaccagggctgccgtgtccctgcctcttcctcccacaggc77640 ccgcgacttggccaggaagatggaggcgctgaagccgctgtttgtggagcccaggagcaa77700 aggcagcttctccgaggtcggcacttggccggggctctgggcctgctgccccctcgtgcc77760 tcccctgcctctcacagcttccccaaggctgaccactggccctgaccatgggctccggcg77820 gctcccgctgcctcttcagggctcctgcgtttccttcctggccctgagtgttgcctctta77880 tcttacaaagcccccagcaccgggtgggtgtggtaacagtggccctcctgtctgagtagc77940 cctagtcggccaccctggccctggggttccccgtgttttctgggaagcactgagcaggcg78000 tggggtcagcctgggatccgtgccaggaagaagcttccagaacccgattggccttcctgg78060 ctaggacgatccttcatcttggagcatgagacctgggtctccctcatgggggaggaaggg78120 gctgggggggggctccaggctcagcctcaccaactttccttccagaccatcagtgcttac78180 tatgcaagggttgccgcccctgggtccaccggcgccaccttcctggcggtctgccggggc78240 aaggtgagctctccagggccctctgccctgacctggttgcctgttccctggtgggtgctt78300 atggctccccagcagactctgggccctgggggctgcccggtcccctccttgggtcccacg78360 agagcgactgctggccctgctgggagcgtgtcctgctctgggcctgggcaggcaggatgg78420 gagtttcctggccacaagagttggaggtggcgtctgggagctgtggaccccaagtggggt78480 cctgacccacagatggagcttcctcccacccctggttggggacggagcctcggggaaggt78540 ggctgggctgggtgtgggcaccagggagaggagcccccacggccccaggcagctccctgg78600 tgtgtcccctaggccagcgaggggctggacttctcagacacgaatggccgtggtgtgatt78660 gtcacgggcctcccgtaccccccacgcatggacccccgggttgtcctcaagatgcagttc78720 ctggatgagatgaagggccagggtggggctgggggccaggtgagttacagcagggtgggg78780 ctggggtaaggcggtctggtgactgagcccccgccccgtggccaagggagcccccgtgac78840 cgagccgcctcgccccacagttcctctctgggcaggagtggtaccggcagcaggcgtcca78900 gggctgtgaaccaggccatcgggcgagtgatccggcaccgccaggactacggagctgtct78960 tcctctgtgaccacaggtgcgtgcagtccggtggcaggcgcggcgccaggggacacgccc79020 acaccccactgggcccctggactctccttccccacatgaggccccgtctcctccagagcc79080 tctccggctactcggggtcagcgtggggcccctgcagcagatgagggtcttcacttcggt79140 gaactgaacccttgaagcggctgtgggcagggcagcagggctatggccaccccccaggtt79200 cgcctttgccgacgcaagagcccaactgccctcctgggtgcgtccccacgtcagggtgta79260 tgacaactttggccatgtcatccgagacgtggcccagttcttccgtgttgccgagcgaac79320 tgtgagttcctgcccagggaggggatgagggtgttgtccccagaggagccagaaatgggt79380 ccacccacccccatggttctgcagatgccagcgccggccccccgggctacagcacccagt79440 gtgcgtggagaagatgctgtcagcgaggccaagtcgcctggccccttcttctccaccagg79500 aaagctaagagtctggacctgcatgtccccagcctgaagcagaggtcctcaggtgcggac79560 gggcagcgctgggtgggcggtgtgggggtggcggagcgggcggcgtggggcgggcagcac79620 caggcgcccagggcggaggcgactcacctggctttgtgcgcttcccctcccacctccaaa79680 ggctgcctctccctcctagggcagggcccccacgggctgcaaccctcccctacaggcaga79740 gaacgccccaggcaaggatgccccccgaggctgagactccccccaatagcagggaggaca79800 cccacaggcaggaccccaagtgctgggactctcccccaagaggggctttgccacaggcag79860 ggaccccagctggggccccccgtgggcttcactgcgcactcgggtgcccctgcagggtca79920 ccagctgccggggaccccgagagtagcctgtgtgtggagtatgagcaggagccagttcct79980 gcccggcagaggcccagggggctgctggccgccctggagcacagcgaacagcgggcgggg80040 agccctggcgaggagcaggtacagttccagggccttgggatggacacagaccctctgtct80100 cctgaggccaacccgaccccgcccatctggcctcaggcacctccccacacacccctgtaa80160 atcccctgcctggcaggcaggcgggcaagcgggcgggggatcccagctgcCtggctgtct80220 gtgggtcctccaccccacctcacccacaggctgctggctcccaggtggtgcatgccctgg80280 ccctccgcgggtgccccccacatcactttggttctctggcgggtcagcttggctcagtgc80340 actcaaggtcgggtgcccctgccactggctgcgcttgaggctggcctttctccaggaatg80400 tgctgcgggtggaacccaggttccttcttccttggggccttttgccccagaagcccataa80460 ttcctcaggccaacccgaaattttctccctgcttcctgctgggagccattcccctcttcc80520 tgcccatccctgcccttcaggcccctggagtgagctccaggtgcaggcaccaggcacctg80580 tgtccccttcctgccagcccctcgctgtggtcggactgtcttccctggacctgctcttac80640 aagtcaccacctgcgagcctcatgagccgctggtgtgacttggacaggaccaagttgtgg80700 cactgtcaccggggtgtgctgtgcccccctcccccgacctccatcttggctcagggctcc80760 ttgggaccatcttccctgtgcgtccaggtgctttgggaccccagagtgtgtggttggggt80820 ctgtgtgtggttgtgagctgtgtcctcctcaggcccacagctgctccaccctgtccctcc80880 tgtctgagaagaggccggcagaagaaccgcgaggagggaggaagaagatccggctggtca80940 gccacccggtgcgtgagctgtccctgcacctgtgccgaccaccatagacacgcatgggaa81000 cgcagccgtgggtgcccccagccacggctggtcccgatgggaccagggaatccaccccca81060 ggagctgatgtccagggcagctgtgatgctgacggccaggggctcaagtgtgtggtttct81120 tctgcagggggctcatgagtcccagctggaatcaggccccacccttgggcaggtttggca81180 tggggcctgcagcactgggcttggccctggcatttccctcaagtgtggatgcacacctgc81240 ctcatgtgagggacacagcccattcctagccttggatcaaagaacggagttatagccgga81300 gccaggaagccccctgcctgctggaaaaccccaagtgtggcggcctttgtccatgtccct81360 tggcttctgggaagaactgggtggtgcccaggcagggctggtgccatcaggaagtgggtg81420 gctgctgaggggcctgggctggcgagggcctgggtggggagtgcctgggccgcccctgcc81480 ttggtttccacgtttccgtgttggtctggggtgtgtagagagatgggcactgctcatccg81540 gaagcccctccttgtgcgctgccatcctgggagcctcagccgcatccgctgtggggcagg81600 gggcttgagggaggaggagagagacgggccatgcaggacccctggcttgaggcagagcca81660 atctaccctttgcccattcactgctctcagttccctgccagcctctcactgtgtgacctc81720 agacgggcccagccccacagctttcttcccgcagcccctccctatgtccatccagccagc81780 cagtttctcaggcagcagccccacctcggcagtcactgtcccagggaacgctcaatgttc81840 caaggaaggctctgcagccccagggaccagatgatgaggctggccctgatggagcctcgg81900 gcctgtgtcctgcaggaggagcccgtggctggtgcacagacggacagggccaagctcttc81960 atggtggccgtgaagcaggagttgagccaagccaactttgccaccttcacccaggccctg82020 caggactacaagggttccgatgacttcgccgccctggccgcctgtctcggccccctcttt82080 gctgaggaccccaagaagcacaacctgctccaaggtgccctggcttgcagaggccaccca82140 ccctgagggcagtgctgccgccgcgtgtggggtgggggccatctgggtccaaggtggtct82200 ctgttctctagagaaaaaggggcagatggggacagacgccccttcctctacaggcttcta82260 ccagtttgtgcggccccaccataagcagcagtttgaggaggtctgtatccagctgacagg82320 acgaggctgtggctatcggcctgagcacagcattccccgaaggcagcgggcacagccggt82380 cctggaccccactggtaaatggggccccaggtgggaccctcagactcctgcgtggaaggc82440 agtgtgggccagagtcctgggctgcttggggtgggcatcctcgggccctgcttggccccg82500 cctctctgttcccctatgggagtgatgggggcctccacctccaccaccagcaccagcagc82560 accacctccaccttcaccaccaccacctccaccaccaccacctccaccacctccacctcc82620 accacctccaccacctccaccacctccaccaccaccaccacctccaccaccaccaccacc82680 accacctccaccaccaccaccaccaccaccacctccacctccaccacctccaccaccacc82740 tccacctccaccaccaccaccacctccacctccaccacctccacctccacctccaccacc82800 accacctccaccaccaccaccaccacctccacctccaccagcagcagcatcacttgttgg82860 ggagaccctgtgcaactccatgcacagccctgtccctgccatagccccgacccctaagca82920 cagccctgtccaactgccacacgtcccctgcctcccatgcatggtcctggggggtcaact82980 gcacacgccagggtcctagggtcctagacccctgtcctccctgtttctgcctctgtttgg83040 ggtggagtccaagtctccagaggcggaagcatctgtgttcgtgtgttaatgaacagcccc83100 tacagagttcccctagttcacccaggggggaacctagcctgttgggacgaccccagatcc83160 cttctgggcttggtactcactgggatatcctcatgcctgcacccagcctacggctctgag83220 ctcctgagtggggctttggcctgcccgccactgttccagcccccatccagcaggctggtg83280 tctcctctgatgcccccagcacccaggcgtgtacctgcctgggttttcccgccctggtct83340 gaggtgggtgaggcctggcctccctagccagccctgcccccccaccccagggaactttcc83400 agatgctcccgaccagctttgtggctctacatctcttcatcaggaagaacggcgccggat83460 cccaagctgaccgtgtccacggctgcagcccagcagctggacccccaagagcacctgaac83520 cagggcaggccccacctgtcgcccaggccacccccaacaggtagctgactcctgaaccgt83580 gtgcagcctacgacttggtgggtccctcagtggcttcacgaggctaactcttgagtgtgg83640 ccggggctgcccctgtggggagccatctcatggtggggactgctcccggttctgcacccc83700 gcagttgtcctgagcagctctccaggagttcctggaggaagggcgggcagggcggtggga83760 ctctcagtcctccaccccagcgccactctgagccatgctactcccacaccaggagaccct83820 ggcagccaaccacagtgggggtctggagtgcccagagcagggaagcagggccagcacgcc83880 gtgagcgcctacctggctgatgcccgcagggccctggggtccgcgggctgtagccaactc83940 ttggcagcgctgacagcctataagcaagacgacgacctcgacaaggtgctggctgtgttg84000 gccgccctgaccactgcaaagccagaggacttccccctgctgcacagcaagtggccctgg84060 cgtggggaacagccggtggggtggggggcaggggacaaaatgggggctgtgccgggtctg84120 attgaagctccccgcagggttcagcatgtttgtgcgtccacaccacaagcagcgcttctc84180 acagacgtgcacagacctgaccggccggccctacccgggcatggagccaccgggacccca84240 ggaggagaggcttgccgtgcctcctgtgcttacccacagggctccccaaccaggtagggc84300 acctgcctggctgctcctggcagcgccccaaccgcacgcagccctgggagtgagcagcaa84360 agccccaggcccccctcagactcaagtctctgtctccaggcccctcacggtccgagaaga84420 ccgggaagacccagagcaagatctcgtccttccttagacagaggccagcagggactgtgg84480 gggcgggcggtgaggatgcaggtcccagccagtcctcaggacctccccacgggcctgcag84540 catctgagtggggtgagcctcatgggagagacatcgctgggcagcaggccacgggagctc84600 cgggcgggcccctctcagcaggctgtgtgtgccagggctgtggggcagaggacgtggtgc84660 ccttccagtgccctgcctgtgacttccagcgctgccaagcctgctggcaacggcaccttc84720 aggttggtgcctggccactacagttcctgctgggtgtagccccaggtgatgggctgaggg84780 ggaaagggcaggcccttgtcctggtggcaacgcctggcagacgtgtgcagtgggccggtt84840 gtctcacaggcctctaggatgtgcccagcctgccacaccgcctccaggaagcagagcgtc84900 atgcaggtcttctggccagagccccagtgagtgcccacggaggcccccagcacacccaac84960 gtggcttgatcacctgcctgtccagctctggtgggccaagaacccacccaacagaatagg85020 ccagcccatgccagccggcttggcccgctgcaggcctcaggcaggcggggcccatggttg85080 gtccctgcggtgggaccggatctgggcctgcctctgagaagccctgagctaccttggggt85140 ctggggtgggtttctgggaaagtgcttccccagaacttccctggctcctggcctgtgagt85200 ggtgccacaggggcaccccagctgagcccctcaccgggaaggaggagacccccgtgggca85260 cgtgtccacttttaatcaggggacagggctctctaataaagctgctggcagtgcccagga85320 cggtgtcttcgtggcctgggcttggtggtgggagttgagggacagggagttggcagaggc85380 ccctcccagcctgccatgtgacactgtacttcctccacggtgggctcagccctgccctca85440 tcctcacagccgcagccaagctgcagttggtaggggatccaccgacacaccaggctgcct85500 gggctggtctctgggttgggagctgccccaggtgctgaggagggcagctccctggctggt85560 gaggcccctcccagaaccacccttggactgagctctggggagggatggtaccaggtgggt85620 gaggggggctgcctggggagggaggggttcctatggggcgtggcgaggctggcccagccc85680 tctccccgcccatatatgtagggcagcagcaggatgggcttctggacttgggcggcccct85740 ccgcaggcggaccgggggcaaaggaggtggcatgtcggtcaggcacagcagggtcctgtg85800 tccgcgctgagccgcgctctccctgctccagcaaggaccatgagggcgctggaggggcca85860 ggcctgtcgctgctgtgcctggtgttggcgctgcctgccctgctgccggtgccggctgta85920 cgcggagtggcagaaacacccacctacccctggcgggacgcagagacaggggagcggctg85980 gtgtgtgcccagtgccccccaggcacctttgtgcagcggccgtgccgccgagacagcccc86040 acgacgtgtggcccgtgtccaccgcgccactacacgcagttctggaactacctggagcgc86100 tgccgctactgcaacgtcctctgcggggagcgtgaggaggaggcacgggcttgccacgcc86160 acccacaaccgcgcctgccgctgccgcaccggcttcttcgcgcacgctggtttctgcttg86220 gagcacgcatcgtgtccacctggtgccggcgtgattgccccgggtgagagctgggcgagg86280 ggaggggcccccaggagtggtggccggaggtgtggcaggggtcaggttgctggtcccagc86340 cttgcaccctgagctaggacaccagttcccctgaccctgttcttccctcctggctgcagg86400 cacccccagccagaacacgcagtgccagccgtgccccccaggcaccttctcagccagcag86460 ttccagctcagagcagtgccagccccaccgcaactgcacggccctgggcctggccctcaa86520 tgtgccaggctcttcctcccatgacacgctgtgcaccagctgcactggcttccccctcag86580 caccagggtaccaggtgagccagaggcctgagggggcagcacactgcaggccaggcccac86640 ttgtgccctcactcctgcccctgcacgtgcatctagcctgaggcatgccagctggctctg86700 ggaaggggccacagtggatttgaggggtcaggggtccctccactagatc~/~~caccaagtc86760 ~

tgccctctcaggggtggctgagaatttggatctgagccagggcacagcctcccctgggga86820 gctctgggaaagtgggcagcaatctcctaactgcccgaggggaaggtggctggctcctct86880 gacacggagaaaccgaggcctgatggtaactctcctaactgcctgagaggaaggtggctg86940 cctcctctgacatggggaaaccgaggcccaatgttaaccactgttgagaagtcacagggg87000 gaagtgacccccttaacatcaagtcaggtccggtccatctgcaggtcccaactcgcccct87060 tccgatggcccaggagccccaagcccttgcctgggcccccttgcctcttgcagccaaggt87120 ccgagtggccactcctgccccctaggcctttgctccagctctctgaccgaaggctcctgc87180 cccttctccagtccccatcgttgcactgccctctccagcacggctcactgcacagggatt87240 tctctctcctgcaaaccccccgagtggggcccagaaagcagggtacctggcagcccccgc87300 cagtgtgtgtgggtgaaatgatcggaccgctgcctccccaccccactgcaggagctgagg87360 agtgtgagcgtgccgtcatcgactttgtggctttccaggacatctccatcaagaggctgc87420 agcggctgctgcaggccctcgaggccccggagggctggggtccgacaccaagggcgggcc87480 gcgcggccttgcagctgaagctgcgtcggcggctcacggagctcctgggggcgcaggacg87540 gggcgctgctggtgcggctgctgcaggcgctgcgcgtggccaggatgcccgggctggagc87600 ggagcgtccgtgagcgcttcctccctgtgcactgatcctggccccctcttatttattcta87660 catccttggcaccccacttgcactgaaagaggcttttttttaaatagaagaaatgaggtt87720 tcttaaagcttatttttataaagctttttcataaaactggttgtagttgcacagctactg87780 ggagggcagccggggacacctgagccgcccgctgtgcccagatccctcaggctgcctgcc87840 atcagaactgctgcccggggcttcccctacctcagacagaccctccctgggaggatcagt87900 ggggagtgccacctctgcccccagtggctgtggcacgtggcaggggcccctgaagctcag87960 cgagggtcagggcctgggagggtatcattgctggaagaacaggatggggctcaggccagc88020 cctagtcgccggggcccacactaaccccccacttatgaattcctcccactcccaactcac88080 aggggatttcccgagaggggacctgccaaagacctcctccaggcctcccatgcttcccgg88140 gaagtgaagcttctccccctctggggcaggctctgaagcctcccgatgcacccagagcaa88200 ccagggggctgcaccagccactcgcctccccagcacggccaggttcccggggctggaggt88260 cccccccaggtcctgggaaccaacctgcagaacacacacagggtcccctggagaggacgc88320 ggggacttccagggcccgactcctgtgagtcacagccccgcagctgctgcgccaccccca88380 ccctgactcatgccccttcccagcagctcctcccaggaccccatgtccttcccacatccg88440 caggaagggagtgcctggactctccaggcccacctggggagcccctcacctgcccaccag88500 cccctgagcagcccagtaacaccatcaccgtgtccaacagccaggagcctccaccctcca88560 ggagggaagggatggacagagccacactcgccgtctttattttgcactcaccctgggtga88620 cactgggcaggccgctcctgcccacagccagactgaggaagaacacagcactcggcaggc88680 ccagtggggtccgtgcagggaggaccccaggaccagccttactcccgagcaggggacaca88740 gggccccacagagaacccctccgggaggttctctcctggctgggggagggctctggaccc88800 ccacaaacactccccaacttgcggggctggggcataaaaacagccactccCagcaggccc88860 cctcagctttttgcatcagtcagctccctcccgggggattagggtgaggtgaagccaggc88920 ccaggcgtggggtataggtcttcccccgcaggcctcagccctgtcccgaggctgcatcac88980 aatccagggcccccgctggcctttgggaacatggcctgggtcttcctcaaggcaagatca89040 gccccagaccacttccggggtcacggggtcacagggcagaagccagatggcagccatggc89100 tgacgggcctcctcctcgatggggcggagacagccacggggtctcccgagggtcccacag89160 ggctgtcctcatgcagcccaagccagcctgagcactggagccccaattcccaaccaggtc89220 tccctcagaccccccagaaagggcctcgaaaggccgccgctgcgccctgtggaaaggctg89280 ccgctgcagggcctgggccagccgggctgccagactcccctccaaagcctccggatgcct89340 acgcttttccagacatagaggaaagtttgtcttcgagaaaacaaagtaaatagaagaacc89400 ccaaagcaaagcaaacccaccccccagatcagcagcatgggagccaacaggaggccactc89460 ctccagcaccaggggaccagccgtcccgacggcagcgcggctgcgcctacgtgatgtccc89520 tctgccgcggcggccggtgcacattccgcacgacacacttcaccatccactcgatgccct89580 cgcgcacccctttgctgtgaagacagcgggtgtgaggcggggggtctcggtccccaaagc89640 ccccgcaggtgcagcccccactcaccctgtgagggccgagcaggcctgggtcaggcaatc89700 gcgcctgccgatcttgctggtgcagtcgctgaaggccgtcttgatgtcagggattgagag89760 gcacgtctgggggaggtaaggccgtgaggagcagcccccacgtctggccctgtcctgcct89820 gtgggcccgggactctcagaagggcgtatgcccttcaccccagggaaacagccagagctc89880 caccagggtcccagtgtctcccacagagaccacagcagtgaggaccctgtgctcagcccg89940 aggctgaacatggctggtagtgcctgagacaaactagacgtccacacggctccaaggagt90000 ccaccccccatcccctccctgggggacaccctgagccccgaggtggggcgctgaggactg90060 aggcctcctgggcagtggcggaggcaggtcccaggggcccacacagccggggatgatgga90120 gaggtgggagccctgcatcagtgatgggggcagtctgcagtcatggtggcttctgctcac90180 aaccacctgcccagtcttcaaaaagcagccctcccctccccttttcctccgaggggagac90240 ccctgccccgtaccagatgtccctcttgtcggctgagattgtaggggaggccagccttac90300 aggctgggggcaacagagccaccccagagaaggcaggaagtgaagattcacccggccctc90360 tggacgccgggctgcttctgtgcaaagccactccaagagaacagctagaactcagcgtgg90420 ccagtgctcccgggggcagtggcacctcagaggggtcttgaggggctgccctgggggtgg90480 ggctggcacagatgccacctccaagggtagcaggaacaggtaagggtcagagctgactcc90540 caccagggccccagcatcacttctttgagctctgagtttcacctgggtgtccccacagct90600 tggccacacactcctgagacacggccgccctcctggggagaggtgccctgcatagcagga90660 agaggcctctgggcgcctgccctgaggtgggagaacctccagggctggcagcagcaggtc90720 tggagaggaaccaagcttgggaagctgctgggggcagggcaggccttgagaatggctctg90780 taccccctgggcagtcactgggcctggggtgtctgggtgcacacctactccccttgctgt90840 gggggaggctggggactcgggaagctgctgcgggaggcaggggtggggctcacctccaca90900 tcctgcttgttggccagcaccaagacggggacaccgcacagcgcctcgctggtcaccacc90960 ttctctggggagggcaggagaggcagcgcctcacacccagcatcctgcctctgactgccc91020 aggggcccacaggcgtggacactgtgacagccactccctctgccccccccccgtcaccca91080 ctaggcaggagcacttctgaccagacactgagcctgccccaggcacagagctgcccaagc91140 tggacctgcccccactcaccatccatccctcccagagcagccaggccgcactcaccaaac91200 gcctgcttggactcagccagcctctcctcgtcggtggagtcaatgacgtagatgacgccg91260 tgacactccgcataatactgggaggaagcaccaggagttggggctcagtccccaccctgc91320 caagggccagcagagccaggcctgtgtcatggccacagtgaggggctcacatgaggaagg91380 ggcaagagggcagcccccaactgcaagacccttctgggatgcattctggggttgcgggga91440 gatctggtggaggtgtccccagacgctgctcctgagaacctgccggcaacctttggcctg91500 atggtggccaaaggtgaaagacagggattgggccaggcgtggtggctcacacttattatc91560 ccaacactttgggaggcagaagcaggaggatcacctgagcccacttcacggccaacctgg91620 gcaacacagtgagactccgtctgtacaaaagcttatggtaatgtgcgcctgcagtcctag91680 ctactcgggaggctgaggtgggaggatggcttgagcctgggaggttgaggctgtagtgag91740 ctctgatcacaccactgcactccagcctgggtgagaatgagagaccctgtctcaaaaaaa91800 agatagggtttgggggctggaggaacctagaccacagcctggcccgttgagggagtgcac91860 ctgtggggctctgtgccagcacctcgcacagggagggagtgtggccatgcggataagact91920 gaccagcaccatctacgaagcgagccttccctgccaggacagggccagagtcactgagct91980 cagacctctgCagcctgggctggtcagtcctgggctcgctggcaacactcctgggcaaga92040 cagggcacagcccctgcagcctcaggtacaagtgctgagccctggaccagatgagtgcac92100 ctctatctcaatcagaaaaaaacacagcaaactccgcgtccacgtggagcagacaacagc92160 tcacatttgccactttgcctccaggctgtgccagctctcctgtccaggcatgagtgccca92220 gagacctagaactggatgctgaccaggtaggacaagctggtggtcagtgtgttaagacac92280 acacacccgagagcatgagaagccaggaggcacagcccaactctccgaaatccttagggt92340 gtctgagcagggagtaccagacaaccccatcccagtgccagacaagcttgtgcacctgca92400 cttcccacagaggagagaagcctgtgcacctgcacttcccacagtggaaaggaggaggcc92460 caaggccaggcccccccacccccaggaacttcccacagtggagaggaggcccaaggccag92520 gcgccctccagggttctgcaggtagcgaggcccccccacccccaggaacttctctggcct92580 acagacaggtcccacacagaggccgccaacccctcaagggaccctgcagtgtgccggctg92640 tctgctgctgacacaagggagcaggcggaccctaaggtggagacctctgtggcaggaggg92700 gcggctctgtggaggctgcagcaagcccagtgagagaatctccacgtggctcctggggct92760 tctgagcagggtggcagaaggttcatgtgcaaccgggtcctggaccatgggaccacgtgg92820 ccagagccacccatcacacctaccaggcacaaggtgcacagcccagcagggccgcagtgg92880 acgggagcgacacctcagggctgagtgcgggcaggacccagagccccacgccccagtgga92940 ggcgtcacagcagtggtcattgtggggtgccccacaaggagggggaagagggaggtgtcc93000 cagcgtggctcctggctggccagctgaccccagtggagcagtcagagggactgtgggtct93060 gagtttttctccccagcagcaatgggagctccccaactgcaaagtgccagccagcctgag93120 agactagtgttacagcaaagaacccaggagctgaggtcctggcacatgccacacatgtgg93180 acaccaacccagggtccagccccaggacgaggccaattcgcaatgacgcccctttctgtg93240 gtgctggctctgcacaaggatgcaggatacaggaaccagggtgggagcaggggcctccct93300 tccggtccctcccagtgacctaggggggtccctgcagctgatcctcccagctctgagctc93360 agcagggtcaggggtcccggccactagagcagcacatactcagcagacacgctgaatgac93420 gagccacagctgcctcatgggcatgacttgcacctcatgtctaggagaccctggtgggca93480 ggagatggggctgccatcccacagctgtcccacagctggggacccagggagccactggcc93540 ccaccacggtggtgtctggagaagggctcagactgccaggaagtcgcaccccagcagaag93600 tggtagtgaattgggagggcactcaaggaagggctgtgcagccccaagaccagcagcaag93660 gatgggctacagtggcccccttaagtctccctcttccagtttcgccttaagagaggccct93720 caggaccttggaggaacccctctccaacgtggaagtgtgggtccacatagggctgcagct93780 gtggccagtgcaggcatctctggccccactgtattcttgcttcatgttggagaacactgc93840 accagcagatggtctcattttggtttctgtgggacccactttggctgcaaagagccacac93900 tgccaggtcacacctgcccagggcagcccacactggggacccaccaggccatggtgtgaa93960 gtcccggccagcctggccccacatggcacagcatagccagttctcctccagggctccctg94020 ctgggccaaccacagctctgcggatcctgctgcctgagtcgacctctcctctcccgtcct94080 ccctgccttcctggtgccgacccccagtgtgcatcctgtacctcgacctgtctcagcatc94140 tgtgcctgagacaccggcctgtgacaagatcatcatcatctgtgtcactccccaagcatg94200 ctgcgcactggacacacaggccctgactcaacttgtcctgtctgacttcagtggtcctac94260 aggatctatcagagatcacttggccatgggagaaatgtcttcttggctagaagtcacagc94320 aggaggggacactttgggggcgcctaggaaaggggaactaggatcaaaaaagagatcagg94380 acctgggcactcagctctagagatggcatcagggcagccaaggcactggggacaccccac94440 acccactgtgccagcctagggcagggagcccgaggaagccacaggctctgccctgctcag94500 tgctggactcagtgcctggcccaggctgagaaggagataaactgcagccttgggggtgtg94560 gggaaggggcaccacactgggatctcagaaatgcccaaaacctgtgtcaaaataggagac94620 tgccgctgtgagaccctgaggagtcttctggtgatcatggaagaacaaatgttaagctag94680 aactgaaggaacctcatcaggggagaggcagccatcctgccgtccccacatctggtcttt94740 gccatttctgtgtcctgtggtggtcagcagcaaggtctctgagccgaaaggaggcactca94800 ctttggaggagtgcagggtccccaggtccccacactttgtcttgtcctgactgagaaaga94860 aacagactgccctgacctctctgacttggccagcgaggttgcccttaggctcaaacccaa94920 gccagggtttgaacattcccagacacttgtaagatgtttaggttgttaacataatgttca94980 ggtttcaaaacattgaaagaaactagccccagccctgaacccagatcccccccggcttca95040 ggcatgaccagtgaacacgcccttctctcactggtcacctgaggatgccgcactctgtca95100 acaggttcccctaatacatgctctgatctgatcgccttggcatttagtgattctttccct95160 ggaattctccactggccccatcgcagggaaCtcccaagtgggaaactcccctaccaccac95220 ttttggggcaacttcagctaagggttcagctgggacaaaacagggagccactcgggaacc95280 tgggacaggaccagagagaaaacccgagggacagagtgggtaaggaaagctgctgaggaa95340 gggcccaaagggcactctggaaagaagtggcactggagggctggggtgggggtggtcctg95400 gccagggagtcttaccttgtcccacaaagactgcagctcttcctgccctcctaagtccca95460 gaacatgagccgagcctttcccacatccacagtgccgactggggagaggaggaaacaggc95520 aaggctcatgaccttggtcctcgacacacccagtcccagctctcccaggggatggggcaa95580 accatgctggtgccactcaaatgagacttgagaggggcccgacagggctgtggccacggg95640 ccagctggactgtgaatatcacggcatcctcaaggccccaaacccacagcctgctattga95700 gacccttactgtttaggcccacggtggtggtgattttggatagactcatccccttgtagt95760 tcttgttaaatcgggttttcgactgctccaggaaggtctgaggagagaggcagaggcgaa95820 acacatcaaggaggggctatactggcttccaaatatccttactcaggtctgttctttaaa95880 agacagaaacagaaacagagcaacactctgctcttcaggaggctggtggtgactatcctg95940 ccgtctcaggtgaaatttggcttccgtctgggtagtgaacgtgcagctgacagcacaaaa96000 ccgaagggggcgccgccaggccgtgggaaaggtgcgcgcaagggcgtgggcactcaccgt96060 cttcccagcattgtccaggcccaggatcaggatgcagtactcgtccttctgaaacatgta96120 Cttgtacaagcccgacagcagcgtgtacatcctgccctgggcaccccaacataggtcagt96180 gtgcagccagaaagcacctcccctcccccgggcttctccacggtggtcagtggcgcccca96240 cgtccagccgaccgctcaggacgagagcctgggggccattcccgactcctcgtccctctc96300 ccaccccgtccctctgtaacttctcccaggtcagccgccactgtgtcctgctcacagcaa96360 tgactgcgacctctccgcatacacatcggttccggcccctcccctgctcgcgggactacc96420 cagccgggtgttcacagtgagctcagccgcgctcccgccctcccccgaggcttcgctccc96480 acgcttcacgcgcgcggaacggggaacacactcgctgcagccccgcctgggccacggcac96540 cctcgagcgccagccccgcgccccacccgggagcagcgagccaccggcgcgctccccagg96600 agcccctgcaggcgccgggtagggacgccccatcaccccatttcttaaaacggggacggc96660 cctggggggagcggactacagggcgggtgagcagcggcgcggctgctcctggagtgcacc96720 tggaggcggcgcgcggctggcagggaacgactgcgaaggaagaacctgggtcgcggcccc96780 cggctacgtccgccccaagccgccgccgccaggtctgaggctccccgacaagcagccaaa96840 gctggctcctgtcacacccgcgtcccacctcgagtcctgggccgcccctcgggcctcgcg96900 cctcaccgcacagcctgcggcctacctgcgtccgccgcgccctcggagccgctgctgctg96960 acccccgctgacctccgctgaccccgcgctaaccccgcgcggcgcctgacgggacgcggg97020 ccggcctcagggaatgagctgaaccgcgtcccagcggcctccgcgctccgcttcccggct97080 gcccccgcgcgccaagcacttccggaagcggcggcgctcgggaggaagtgccgatcggct97140 gctggggcgaaaagggggcgccgggccgctctagccggtgaggccggcgggctctctgtg97200 gctgcggctgggaaaccgcgcggaggaggtgcccggccggggaccaggtggccgcggttt97260 gcggggacgcggccctggccagacagaagagacgccgggcgggggggcgcggccggcctg97320 gaaggcggcgggcgcggcgggtgggctcggcggagggtgaggcggcggggcgccccgcgg97380 ggaaggggctccggagtgacgcgggacccggctagcggcgagcccacggcggctcggaag97440 ggaagcgcggagcctgagcgggggtacccgggctgcgacctctgcgctgggagctgtgcc97500 tctgagccggtgtctccccgagggaaaggggacgtgcccgtgcccgtgcccgccctcagg97560 ctgtggggtcggtcccgagacgcggggctcagctggcttctcttcttgcagccctggtcc97620 agcgcctccctctctcagcatggacgaggagagcctggagtcggccttgcagacctaccg97680 tgcgcagctgcagcaggtggagctggccttgggcgccggcctggattcgtctgagcaggc97740 tgacctgcgccagctgcagggggacctgaaggagctcatcgagctcaccgaggccagcct97800 ggtgtctgtcaggaagagcaggttgttggccgcgctggacgaagagcgcccgggccgcca97860 ggaagatgctgagtaccaggctttccgggaggccatcactgaggcggtggaggcaccagc97920 agcggcccgtgggtccggatcagagaccgttcctaaagcagaggcggggccagaatctgc97980 ggcaggtgggcaggaggaggaagagggagaggacgaggaagagctgagtgggacaaaggt98040 gagcgcgccctactacagctcctggggcactctggagtatcacaacgccatggtggtggg98100 aacggaagaggcggaggatggctcggcgggtgtccgtgtgctttacctgtaccccactca98160 caagtctctgaagccgtgcccgttcttcctggagggaaagtgccgctttaaggagaactg98220 caggtaaagccctttgttgtcagatgccaaccttaggggcgtaaggggcacgcacacagg98280 gtcgggtcaggatcggccctccctttgctttgcagttttgtctcagcttcctggggcagg98340 cgtgctttgacagctgtgtctgtgttcaggcgtctacgtcttccttctggggtgaatcaa98400 gaagcatggaaggaggccaggcgcggtggctcacgcctgtaatcccagcactttaggaag98460 ccgaggcgggcagatcacctgaggtcaggagttcaagaccacgctggtcaacatggtgaa98520 accccatctccttaaaaacacaaaaatgaaccggtcgtggtggcgcgcacctgtggtcct98580 ggctactcaggaggctgaggcaggagaattggttgaacccaggaggccgagtttgcagtg98640 agtggagatgcagccactgtactgcagcccgagcagcagtgcaaggcttatgtggaagag98700 agtaggtctccagcctatcgtcagtttttttttggtggttgttttaattttttttgagac98760 agggtcttactttgtcaaccaggctggagtgcagtggcatagtcctggctcactgcagcc98820 tggacctcctgggctcaaccgatcctcctgcctcagcccccctaggagctgggctacaga98880 ctcacgctactacacccagctaatttttatattactataattttttatcttttttttgag98940 acggagtcttgttctgttgcccaggctggagtgcagtggcgtgatctcggctcactgcaa99000 gctccgcctcccgggttcacgccattctcctgcctcagcctcccgagtagctgggactac99060 aggcgcccgccaccatgtctggctaattttctgtatttttagtagagacggggtttcacc99120 atgttagccaggatggtctcaatctcctgacctcgtgatccgcccaccttggcctcccaa99180 agtgctgggatgacaagcgtgagccaccgcgcctggccttttttttttggagacagagtt99240 tcactctcctcacccaggctggagtgtagtggcgcaatctcagcttaccgcaacctctgt99300 ctcccgggttgaagtaattctctacctcagcgtccagagtagctggcattacaggcgccc99360 gccaccacactcggctaattttttgtatttttagtagagtcggagattcaccatcttggc99420 caggctggtcttgaactcctgacctcgtgatccacccaccttggcctcccaaagtgctgg99480 gatcacaggcgtgagccactgcgcctggccctgttgttagttttattctctagagttcaa99540 cttttaaattttactttcatggagattttcaaacataccccaaattagagagtttagcat99600 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 ccttgccacc 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 ctgctcagcc 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 gacgacagag 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 tttggttaga 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 gataatgtgg 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 aaggcaagcc cttcagggag 111180 acactagaaa gatccaaatg 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 ggcagtggct 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 <210>SEQ ID N0:4 <211>LENGTH: 25 <212>TYPE: DNA

<213>ORGANISM: Artificial Sequence <220>FEATURE:

<223>OTHER INFORMATION: oligonucleotide <400>SEQ ID N0:4 cacaggttca 25 gcatgtttgt gcgtc <210>SEQ ID N0:5 <211>LENGTH: 25 <212>TYPE: DNA

<213>ORGANISM: Artificial Sequence <220>FEATURE:

<223>OTHER INFORMATION: oligonucleotide <400>SEQ ID N0:5 cacagtccct 25 gctggcctct gtcta <210>SEQ ID N0:6 <211>LENGTH: 25 <212>TYPE: DNA

<213>ORGANISM: Artificial Sequence <220>FEATURE:

<223>OTHER INFORMATION: oligonucleotide <400>SEQ ID N0:6 caggacatct 25 ccatcaagag gctgc <210>SEQ ID N0:7 <211>LENGTH: 25 <212>TYPE: DNA

<213>ORGANISM: Artificial Sequence <220>FEATURE:

<223>OTHER INFORMATION: oligonucleotide <400>SEQ ID N0:7 aataagaggg 25 ggccaggatc agtgc <210>SEQ ID N0:8 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM: Artificial Sequence cgcctcccag gttcacgcca ttctcctgcc tcagcctcct gagtagctgg gactacaggc 111840 acccccacca cacccggcta attttgtatt tttagtagag atgaggtttc <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:8 gtgaatggca tcctggagag 20 <210> SEQ ID N0:9 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: ArtificialSequence <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:9 gtctccaggc agctcaacag 20 <210> SEQ ID NO:10 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: ArtificialSequence <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:10 accctgtccc tcctgtctga 20 <210> SEQ ID N0:11 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: ArtificialSequence <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:11 agaccctaag atgttcggag 20 <210> SEQ ID N0:12 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: ArtificialSequence <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:12 gatgacctgt gtgagttgcg 20 <210> SEQ ID N0:13 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: ArtificialSequence <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:13 cgcaactcac acaggtcatc 20 <210>SEQ ID N0:14 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM: ArtificialSequence <220>FEATURE:

<223>OTHER INFORMATION:oligonucleotide <400>SEQ ID N0:14 ggagtcaggt 20 caaaggatgc <210>SEQ ID N0:15 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM: ArtificialSequence <220>FEATURE:

<223>OTHER INFORMATION:oligonuCleotide <400>SEQ ID N0:15 gcatcctttg 20 acctgactcc <210>SEQ ID N0:16 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM:ArtificialSequence <220>FEATURE:

<223>OTHER INFORMATION:oligonucleotide <400>SEQ ID N0:16 ggtctgaaac 20 gtgatctggg <210>SEQ ID N0:17 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM: ArtificialSequence <220>FEATURE:

<223>OTHER INFORMATION:oligonucleotide <400>SEQ ID N0:17 cccagatcac 20 gtttcagacc <210>SEQ ID N0:18 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM: ArtificialSequence <220>FEATURE:

<223>OTHER INFORMATION:oligonuCleotide <400>SEQ ID N0:18 cgatgatgtg 20 tgggttctcc <210>SEQ ID N0:19 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM:ArtificialSequence , <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:19 ggagaaccca cacatcatcg 20 <210> SEQ ID N0:20 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: ArtificialSequence <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:20 cgtgtctgag aagtccagcc 20 <210> SEQ ID N0:21 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM:ArtificialSequence , <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:21 ggctggactt ctcagacacg 20 <210> SEQ ID N0:22 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: ArtificialSequence <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:22 acagcatctt ctccacgcac 20 <210> SEQ ID N0:23 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: ArtificialSequence <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:23 agtcctctgg ctttgcagtg 20 <210> SEQ ID N0:24 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: ArtificialSequence <220> FEATURE:

<223> OTHER INFORMATION:oligonucleotide <400> SEQ ID N0:24 tgtgcgtgga gaagatgctg 20 <210>SEQ ID N0:25 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM: ArtificialSequence <220>FEATURE:

<223>OTHER INFORMATION:oligonucleotide <400>SEQ ID N0:25 ggctggaaag 20 ggaagtctac <210>SEQ ID N0:26 <211>LENGTH: 20 <212>TYPE. DNA

<213>ORGANISM: ArtificialSequence <220>FEATURE:

<223>OTHER INFORMATION:oligonucleotide <400>SEQ ID N0:26 tggttcaggt 20 gctcttgggg <210>SEQ ID N0:27 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM: ArtificialSequence <220>FEATURE:

<223>OTHER INFORMATION:oligonucleotide <400>SEQ ID N0:27 cgtgaagcag 20 gagttgagcc <210>SEQ ID N0:28 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM: ArtificialSequence <220>FEATURE:

<223>OTHER INFORMATION:oligonuCleotide <400>SEQ ID N0:28 atcttgctct 20 gggtcttccc <210>SEQ ID N0:29 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM: ArtificialSequence <220>FEATURE:

<223>OTHER INFORMATION:oligonucleotide <400>SEQ ID N0:29 cactgcaaag 20 ccagaggact <210>SEQ ID N0:30 <211>LENGTH: 20 <212>TYPE: DNA

<213>ORGANISM: ArtificialSequence <220> FEATURE:

<223> OTHER INFORMATION: oligonucleotide <400> SEQ ID N0:30 ataagcaaga cgacgacctc 20 <210> SEQ ID N0:31 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: oligonucleotide <400> SEQ ID N0:31 ctattctgtt gggtgggttc 20 <210> SEQ ID N0:32 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: oligonucleotide <400> SEQ ID N0:32 cgtgcctcct gtgcttaccc 20 <210> SEQ ID N0:33 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: oligonucleotide <400> SEQ ID N0:33 cagaccccaa ggtagctcag 20 <210> SEQ ID N0:34 <211> LENGTH: 20 <212> TYPE: DNA

<213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: oligonucleotide <400> SEQ ID N0:34 ggaagaccca gagcaagatc 20 <210> SEQ ID N0:35 <211> LENGTH: 780 <212> TYPE: PRT

<213> ORGANISM:Dictyostelium discoideum <400> SEQ ID N0:35 Met Lys Phe Tyr Ile Glu Asp Leu Leu Val Tyr Phe Pro Tyr Ser Tyr Ile Tyr Pro Glu Gln Tyr Ser Tyr Met Val Ala Leu Lys Arg Ser Leu Asp Asn Gly Gly Pro Cys Ile Leu Glu Met Pro Ser Gly Thr Gly Lys Thr Val Ser Leu Leu Ser Leu Ile Ser Ser Tyr Gln Val Lys Asn Pro Ser Ile Lys Leu Ile Tyr Cys Ser Arg Thr Val Pro Glu Ile Glu Gln Ala Thr Glu Glu Ala Arg Arg Val Leu Gln Tyr Arg Asn Ser Glu Met Gly Glu Glu Ser Pro Lys Thr Leu Cys Met Ser Met Ser Ser Arg Arg Asn Leu Cys Ile Gln Pro Arg Val Ser Glu Glu Arg Asp Gly Lys Val Val Asp Ala Leu Cys Arg Glu Leu Thr Ser Ser Trp Asn Arg Glu Ser Pro Thr Ser Glu Lys Cys Lys Phe Phe Glu Asn Phe Glu Ser Asn Gly Lys Glu Ile Leu Leu Glu Gly Val Tyr Ser Leu Glu Asp Leu Lys Glu Tyr Gly Leu Lys His Gln Met Cys Pro Tyr Phe Leu Ser Arg His Met Leu Asn Phe Ala Asn Ile Val Ile Phe Ser Tyr Gln Tyr Leu Leu Asp Pro Lys Ile Ala Ser Leu Ile Ser Ser Ser Phe Pro Ser Asn Ser Ile Val Val Phe Asp Glu Ala His Asn Ile Asp Asn Val Cys Ile Asn Ala Leu Ser Ile Asn Ile Asp Asn Lys Leu Leu Asp Thr Ser Ser Lys Asn Ile Ala Lys Ile Asn Lys Gln Ile Glu Asp Ile Lys Lys Val Asp Glu Lys Arg Leu Lys Asp Glu Tyr Gln Arg Leu Val Asn Gly Leu Ala Arg Ser Gly Ser Thr Arg Ala Asp Glu Thr Thr Ser Asp Pro Val Leu Pro Asn Asp Val Ile Gln Glu Ala Val Pro Gly Asn Ile Arg Lys Pro Ser Ile Phe Ile Ser Leu Leu Arg Arg Val Val Asp Tyr Leu Arg Glu Pro Asp Lys Ser Arg Leu Lys Ser Gln Met Leu Leu Ser Glu Ser Pro Leu Ala Phe Leu Gln Gly Leu Tyr His Ala Thr Gln Ile Ser Ser Arg Thr Leu Arg Phe Cys Ser Ser Arg Leu Ser Ser Leu Leu Arg Thr Leu Arg Ile Asn Asp Val Asn Gln Phe Ser Gly Ile Ser Leu Ile Ala Asp Phe Ala Thr Leu Val Gly Thr Tyr Asn Asn Gly Phe Leu Ile Ile Ile Glu Pro Tyr Tyr Gln Arg Gln Asn Asn Thr Tyr Asp Gln Ile Phe Gln Phe Cys Cys Leu Asp Ala Ser Ile Gly Met Lys Pro Ile Phe Asp Lys Tyr Arg Ser Val Val Ile Thr Ser Gly Thr Leu Ser Pro Leu Asp Ile Tyr Thr Lys Met Leu Asn Phe Arg Pro Thr Val Val Glu Arg Leu Thr Met Ser Leu Asn Arg Asn Cys Ile Cys Pro Cys Ile Leu Thr Arg Gly Ser Asp Gln Ile Ser Ile Ser Thr Lys Phe Asp Val Arg Ser Asp Thr Ala Val Val Arg Asn Tyr Gly Ala Leu Leu Val Glu Val Ser Ala Ile Val Pro Asp Gly Ile Ile Cys Phe Phe Thr Ser Tyr Ser Tyr Met Glu Gln Ile Val Ser Val Trp Asn Glu Met Gly Leu Leu Asn Asn Ile Leu Thr Asn Lys Leu Ile Phe Val Glu Thr Ser Asp Pro Ala Glu Ser Ala Leu Ala Leu Gln Asn Tyr Lys Lys Ala Cys Asp Ser Gly Arg Gly Ala Val Leu Leu Ser Val Ala Arg Gly Lys Val Ser Glu Gly Ile Asp Phe Asp Asn Gln Tyr Gly Arg Cys Val Ile Leu Tyr Gly Ile Pro Tyr Ile Asn Thr Glu Ser Lys Val Leu Arg Ala Arg Leu Glu Phe Leu Arg Asp Arg Tyr Gln Ile Arg Glu Asn Glu Phe Leu Thr Phe Asp Ala Met Arg Thr Ala Ser Gln Cys Val Gly Arg Val Ile Arg Gly Lys Ser Asp Tyr Gly Ile Met Ile Phe Ala Asp Lys Arg Tyr Asn Arg Leu Asp Lys Arg Asn Lys Leu Pro Gln Trp Ile Leu Gln Phe Cys Gln Pro Gln His Leu Asn Leu Ser Thr Asp Met Ala Ile Ser Leu Ser Lys Thr Phe Leu Arg Glu Met Gly Gln Pro Phe Ser Arg Glu Glu Gln Leu Gly Lys Ser Leu Trp Ser Leu Glu His Val Glu Lys Gln Ser Thr Ser Lys Pro Pro Gln Gln Gln Asn Ser Ala Ile Asn Ser Thr Ile Thr Thr Ser Thr Thr Thr Thr Thr Thr Thr Ser Thr Ile Ser Glu Thr His Leu Thr <210> SEQ ID N0:36 <211> LENGTH: 778 <212> TYPE: PRT
<213> ORGANISM: S. cerevisiae <400> SEQ ID N0:36 Met Lys Phe Tyr Ile Asp Asp Leu Pro Val Leu Phe Pro Tyr Pro Lys Ile Tyr Pro Glu Gln Tyr Asn Tyr Met Cys Asp Ile Lys Lys Thr Leu Asp Val Gly Gly Asn Ser Ile Leu Glu Met Pro Ser Gly Thr Gly Lys Thr Val Ser Leu Leu Ser Leu Thr Ile Ala Tyr Gln Met His Tyr Pro Glu His Arg Lys Ile Ile Tyr Cys Ser Arg Thr Met Ser Glu Ile Glu Lys Ala Leu Val Glu Leu Glu Asn Leu Met Asp Tyr Arg Thr Lys Glu Leu Gly Tyr Gln Glu Asp Phe Arg Gly Leu Gly Leu Thr Ser Arg Lys Asn Leu Cys Leu His Pro Glu Val Ser Lys Glu Arg Lys Gly Thr Val Val Asp Glu Lys Cys Arg Arg Met Thr Asn Gly Gln Ala Lys Arg Lys Leu Glu Glu Asp Pro Glu Ala Asn Val Glu Leu Cys Glu Tyr His Glu Asn Leu Tyr Asn Ile Glu Val Glu Asp Tyr Leu Pro Lys Gly Val Phe Ser Phe Glu Lys Leu Leu Lys Tyr Cys Glu Glu Lys Thr Leu Cys Pro Tyr Phe Ile Val Arg Arg Met Ile Ser Leu Cys Asn Ile Ile Ile Tyr Ser Tyr His Tyr Leu Leu Asp Pro Lys Ile Ala Glu Arg Val Ser Asn Glu Val Ser Lys Asp Ser Ile Val Ile Phe Asp Glu Ala His Asn Ile Asp Asn Val Cys Ile Glu Ser Leu Ser Leu Asp Leu Thr Thr Asp Ala Leu Arg Arg Ala Thr Arg Gly Ala Asn Ala Leu Asp Glu Arg Ile Ser Glu Val Arg Lys Val Asp Ser Gln Lys Leu Gln Asp Glu Tyr Glu Lys Leu Val Gln Gly Leu His Ser Ala Asp Ile Leu Thr Asp Gln Glu Glu Pro Phe Val Glu Thr Pro Val Leu Pro Gln Asp Leu Leu Thr Glu Ala Ile Pro Gly Asn Ile Arg Arg Ala Glu His Phe Val Ser Phe Leu Lys Arg Leu Ile Glu Tyr Leu Lys Thr Arg Met Lys Val Leu His Val Ile Ser Glu Thr Pro Lys Ser Phe Leu Gln His Leu Lys Gln Leu Thr Phe Ile Glu Arg Lys Pro Leu Arg Phe Cys Ser Glu Arg Leu Ser Leu Leu Val Arg Thr Leu Glu Val Thr Glu Val Glu Asp Phe Thr Ala Leu Lys Asp Ile Ala Thr Phe Ala Thr Leu Ile Ser Thr Tyr Glu Glu Gly Phe Leu Leu Ile Ile Glu Pro Tyr Glu Ile Glu Asn Ala Ala Val Pro Asn Pro Ile Met Arg Phe Thr Cys Leu Asp Ala Ser Ile Ala Ile Lys Pro Val Phe Glu Arg Phe Ser Ser Val Ile Ile Thr Ser Gly Thr Ile Ser Pro Leu Asp Met Tyr Pro Arg Met Leu Asn Phe Lys Thr Val Leu Gln Lys Ser Tyr Ala Met Thr Leu Ala Lys Lys Ser Phe Leu Pro Met Ile Ile Thr Lys Gly Ser Asp Gln Val Ala Ile Ser Ser Arg Phe Glu Ile 5'00 505 510 Arg Asn Asp Pro Ser Ile Val Arg Asn Tyr Gly Ser Met Leu Val Glu Phe Ala Lys Ile Thr Pro Asp Gly Met Val Val Phe Phe Pro Ser Tyr Leu Tyr Met Glu Ser Ile Val Ser Met Trp Gln Thr Met Gly Ile Leu Asp Glu Val Trp Lys His Lys Leu Ile Leu Val Glu Thr Pro Asp Ala Gln Glu Thr Ser Leu Ala Leu Glu Thr Tyr Arg Lys Ala Cys Ser Asn Gly Arg Gly Ala Ile Leu Leu Ser Val Ala Arg Gly Lys Val Ser Glu Gly Ile Asp Phe Asp His Gln Tyr Gly Arg Thr Val Leu Met Ile Gly Ile Pro Phe Gln Tyr Thr Glu Ser Arg Ile Leu Lys Ala Arg Leu Glu Phe Met Arg Glu Asn Tyr Arg Ile Arg Glu Asn Asp Phe Leu Ser Phe Asp Ala Met Arg His Ala Ala Gln Cys Leu Gly Arg Val Leu Arg Gly Lys Asp Asp Tyr Gly Val Met Val Leu Ala Asp Arg Arg Phe Ser Arg Lys Arg Ser Gln Leu Pro Lys Trp Ile Ala Gln Gly Leu Ser Asp Ala Asp Leu Asn Leu Ser Thr Asp Met Ala Ile Ser Asn Thr Lys Gln Phe Leu Arg Thr Met Ala Gln Pro Thr Asp Pro Lys Asp Gln Glu Gly Val Ser Val Trp Ser Tyr Glu Asp Leu Ile Lys His Gln Asn Ser Arg Lys Asp Gln Gly Gly Phe Ile Glu Asn Glu Asn Lys Glu Gly Glu Gln Asp Glu Asp Glu Asp Glu Asp Ile Glu Met Gln <210> SEQ ID N0:37 <211> LENGTH: 772 <212> TYPE: PRT
<213> ORGANISM: S. pombe <400> SEQ ID N0:37 Met Lys Phe Tyr Ile Asp Asp Leu Pro Ile Leu Phe Pro Tyr Pro Arg Ile Tyr Pro Glu Gln Tyr Gln Tyr Met Cys Asp Leu Lys His Ser Leu Asp Ala Gly Gly Ile Ala Leu Leu Glu Met Pro Ser Gly Thr Gly Lys Thr Ile Ser Leu Leu Ser Leu Ile Val Ser Tyr Gln Gln His Tyr Pro Glu His Arg Lys Leu Ile Tyr Cys Ser Arg Thr Met Ser Glu Ile Asp Lys Ala Leu Ala Glu Leu Lys Arg Leu Met Ala Tyr Arg Thr Ser Gln Leu Gly Tyr Glu Glu Pro Phe Leu Gly Leu Gly Leu Thr Ser Arg Lys Asn Leu Cys Leu His Pro Ser Val Arg Arg Glu Lys Asn Gly Asn Val Val Asp Ala Arg Cys Arg Ser Leu Thr Ala Gly Phe Val Arg Glu Gln Arg Leu Ala Gly Met Asp Val Pro Thr Cys Glu Phe His Asp Asn Leu Glu Asp Leu Glu Pro His Ser Leu Ile Ser Asn Gly Val Trp Thr Leu Asp Asp Ile Thr Glu Tyr Gly Glu Lys Thr Thr Arg Cys Pro Tyr Phe Thr Val Arg Arg Met Leu Pro Phe Cys Asn Val Ile Ile Tyr Ser Tyr His Tyr Leu Leu Asp Pro Lys Ile Ala Glu Arg Val Ser Arg Glu Leu Ser Lys Asp Cys Ile Val Val Phe Asp Glu Ala His Asn Ile Asp Asn Val Cys Ile Glu Ser Leu Ser Ile Asp Leu Thr Glu Ser Ser Leu Arg Lys Ala Ser Lys Ser Ile Leu Ser Leu Glu Gln Lys Val Asn Glu Val Lys Gln Ser Asp Ser Lys Lys Leu Gln Asp Glu Tyr Gln Lys Leu Val Arg Gly Leu Gln Asp Ala Asn Ala Ala Asn Asp Glu Asp Gln Phe Met Ala Asn Pro Val Leu Pro Glu Asp Val Leu Lys Glu Ala Val Pro Gly Asn Ile Arg Arg Ala Glu His Phe Ile Ala Phe Leu Lys Arg Phe Val Glu Tyr Leu Lys Thr Arg Met Lys Val Leu His Val Ile Ala Glu Thr Pro Thr Ser Phe Leu Gln His Val Lys Asp Ile Thr Phe Ile Asp Lys Lys Pro Leu Arg Phe Cys Ala Glu Arg Leu Thr Ser Leu Val Arg Ala Leu Gln Ile Ser Leu Val Glu Asp Phe His Ser Leu Gln Gln Val Val Ala Phe Ala Thr Leu Val Ala Thr Tyr Glu Arg Gly Phe Ile Leu Ile Leu Glu Pro Phe Glu Thr Glu Asn Ala Thr Val Pro Asn Pro Ile Leu Arg Phe Ser Cys Leu Asp Ala Ser Ile Ala Ile Lys Pro Val Phe Glu Arg Phe Arg Ser Val Ile Ile Thr Ser Gly Thr Leu Ser Pro Leu Asp Met Tyr Pro Lys Met Leu Gln Phe Asn Thr Val Met Gln Glu Ser Tyr Gly Met Ser Leu Ala Arg Asn Cys Phe Leu Pro Met Val Val Thr Arg Gly Ser Asp Gln Val Ala Ile Ser Ser Lys Phe Glu Ala Arg Asn Asp Pro Ser Val Val Arg Asn Tyr Gly Asn Ile Leu Val Glu Phe Ser Lys Ile Thr Pro Asp Gly Leu Val Ala Phe Phe Pro Ser Tyr Leu Tyr Leu Glu Ser Ile Val Ser Ser Trp Gln Ser Met Gly Ile Leu Asp Glu Val Trp Lys Tyr Lys Leu Ile Leu Val Glu Thr Pro Asp Pro His Glu Thr Thr Leu Ala Leu Glu Thr Tyr Arg Ala Ala Cys Ser Asn Gly Arg Gly Ala Val Leu Leu Ser Val Ala Arg Gly Lys Val Ser Glu Gly Val Asp Phe Asp His His Tyr Gly Arg Ala Val Ile Met Phe Gly Ile Pro Tyr Gln Tyr Thr Glu Ser Arg Val Leu Lys Ala Arg Leu Glu Phe Leu Arg Asp Thr Tyr Gln Ile Arg Glu Ala Asp Phe Leu Thr Phe Asp Ala Met Arg His Ala Ala Gln Cys Leu Gly Arg Val Leu Arg Gly Lys Asp Asp His Gly Ile Met Val Leu Ala Asp Lys Arg Tyr Gly Arg Ser Asp Lys Arg Thr Lys Leu Pro Lys Trp Ile Gln Gln Tyr Ile Thr Glu Gly Ala Thr Asn Leu Ser Thr Asp Met Ser Leu Ala Leu Ala Lys Lys Phe Leu Arg Thr Met Ala Gln Pro Phe Thr Ala Ser Asp Gln Glu Gly Ile Ser Trp Trp Ser Leu Asp Asp Leu Leu Ile His Gln Lys Lys Ala Leu Lys Ser Ala Ala Ile Glu Gln Ser Lys His Glu Asp Glu Met Asp Ile Asp Val Val Glu Thr <210> SEQ ID N0:38 <211> LENGTH: 760 <212> TYPE: PRT
<213> ORGANISM: Homo sapien <400> SEQ ID N0:38 Met Lys Leu Asn Val Asp Gly Leu Leu Val Tyr Phe Pro Tyr Asp Tyr Ile Tyr Pro Glu Gln Phe Ser Tyr Met Arg Glu Leu Lys Arg Thr Leu Asp Ala Lys Gly His Gly Val Leu Glu Met Pro Ser Gly Thr Gly Lys Thr Val Ser Leu Leu Ala Leu Ile Met Ala Tyr Gln Arg Ala Tyr Pro Leu Glu Val Thr Lys Leu Ile Tyr Cys Ser Arg Thr Val Pro Glu Ile Glu Lys Val Ile Glu Glu Leu Arg Lys Leu Leu Asn Phe Tyr Glu Lys Gln Glu Gly Glu Lys Leu Pro Phe Leu Gly Leu Ala Leu Ser Ser Arg Lys Asn Leu Cys Ile His Pro Glu Val Thr Pro Leu Arg Phe Gly Lys Asp Val Asp Gly Lys Cys His Ser Leu Thr Ala Ser Tyr Val Arg Ala Gln Tyr Gln His Asp Thr Ser Leu Pro His Cys Arg Phe Tyr Glu Glu Phe Asp Ala His Gly Arg Glu Val Pro Leu Pro Ala Gly Ile Tyr Asn Leu Asp Asp Leu Lys Ala Leu Gly Arg Arg Gln Gly Trp Cys Pro Tyr Phe Leu Ala Arg Tyr Ser Ile Leu His Ala Asn Val Val Val Tyr Ser Tyr His Tyr Leu Leu Asp Pro Lys Ile Ala Asp Leu Val Ser Lys Glu Leu Ala Arg Lys Ala Val Val Val Phe Asp Glu Ala His Asn Ile Asp Asn Val Cys Ile Asp Ser Met Ser Val Asn Leu Thr Arg Arg Thr Leu Asp Arg Cys Gln Gly Asn Leu Glu Thr Leu Gln Lys Thr Val Leu Arg Ile Lys Glu Thr Asp Glu Gln Arg Leu Arg Asp Glu Tyr Arg Arg Leu Val Glu Gly Leu Arg Glu Ala Ser Ala Ala Arg Glu Thr Asp Ala His Leu Ala Asn Pro Val Leu Pro Asp Glu Val Leu Gln Glu Ala Val Pro Gly Ser Ile Arg Thr Ala Glu His Phe Leu Gly Phe Leu Arg Arg Leu Leu Glu Tyr Val Lys Trp Arg Leu Arg Val Gln His Val Val Gln Glu Ser Pro Pro Ala Phe Leu Ser Gly Leu Ala Gln Arg Val Cys Ile Gln Arg Lys Pro Leu Arg Phe Cys Ala Glu Arg Leu Arg Ser Leu Leu His Thr Leu Glu Ile Thr Asp Leu Ala Asp Phe Ser Pro Leu Thr Leu Leu Ala Asn Phe Ala Thr Leu Val Ser Thr Tyr Ala Lys Gly Phe Thr Ile Ile Ile Glu Pro Phe Asp Asp Arg Thr Pro Thr Ile Ala Asn Pro Ile Leu His Phe Ser Cys Met Asp Ala Ser Leu Ala Ile Lys Pro Val Phe Glu Arg Phe Gln Ser Val Ile Ile Thr Ser Gly Thr Leu Ser Pro Leu Asp Ile Tyr Pro Lys Ile Leu Asp Phe His Pro Val Thr Met Ala Thr Phe Thr Met Thr Leu Ala Arg Val Cys Leu Cys Pro Met Ile Ile Gly Arg Gly Asn Asp Gln Val Ala Ile Ser Ser Lys Phe Glu Thr Arg Glu Asp Ile Ala Val Ile Arg Asn Tyr Gly Asn Leu Leu Leu Glu Met Ser Ala Val Val Pro Asp Gly Ile Val Ala Phe Phe Thr Ser Tyr Gln Tyr Met Glu Ser Thr Val Ala Ser Trp Tyr Glu Gln Gly Ile Leu Glu Asn Ile Gln Arg Asn Lys Leu Leu Phe Ile Glu Thr Gln Asp Gly Ala Glu Thr Ser Val Ala Leu Glu Lys Tyr Gln Glu Ala Cys Glu Asn Gly Arg Gly Ala Ile Leu Leu Ser Val Ala Arg Gly Lys Val Ser Glu Gly Ile Asp Phe Val His His Tyr Gly Arg Ala Val Ile Met Phe Gly Val Pro Tyr Val Tyr Thr Gln Ser Arg Ile Leu Lys Ala Arg Leu Glu Tyr Leu Arg Asp Gln Phe Gln Ile Arg Glu Asn Asp Phe Leu Thr Phe Asp Ala Met Arg His Ala Ala Gln Cys Val Gly Arg Ala Ile Arg Gly Lys Thr Asp Tyr Gly Leu Met Val Phe Ala Asp Lys Arg Phe Ala Arg Gly Asp Lys Arg Gly Lys Leu Pro Arg Trp Ile Gln Glu His Leu Thr Asp Ala Asn Leu Asn Leu Thr Val Asp Glu Gly Val Gln Val Ala Lys Tyr Phe Leu Arg Gln Met Ala Gln Pro Phe His Arg Glu Asp Gln Leu Gly Leu Ser Leu Leu Ser Leu Glu Gln Leu Glu Ser Glu Glu Thr Leu Lys Arg Ile Glu Gln Ile Ala Gln Gln Leu

Claims (26)

WHAT IS CLAIMED IS:

1. A purified DNA molecule encoding a mammalian NHL protein.

2. A purified DNA molecule of claim 1 encoding a human NHL protein which comprises the amino acid sequence MPKIVLNGVT VDFPFQPYKC QQEYMTKVLE CLQQKVNGIL ESPTGTGKTL CLLCTTLAWR
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 ELEDIAKLKM 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* (SEQ ID NO:2).

3. An expression vector for expressing a NHL protein in a recombinant host cell wherein said expression vector comprises a DNA molecule of claim 2.

4. A host cell which expresses a recombinant NHL protein wherein said host cell contains the expression vector of claim 3.

5. A process for expressing a NHL protein in a recombinant host cell, comprising:
(a) transfecting the expression vector of claim 3 into a suitable host cell;
and, (b) culturing the host cells of step (a) under conditions which allow expression of said NHL protein from said expression vector.

6. A purified DNA molecule encoding a human NHL protein which consists of the amino acid sequence MPKIVLNGVT VDFPFQPYKC QQEYMTKVLE CLQQKVNGIL ESPTGTGKTL CLLCTTLAWR
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 ELEDIAKLKM 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* (SEQ ID NO:2).

7. An expression vector for expressing a NHL protein in a recombinant host cell wherein said expression vector comprises a DNA molecule of claim 6.

8. A host cell which expresses a recombinant NHL protein wherein said host cell contains the expression vector of claim 7.

9. A process for expressing a NHL protein in a recombinant host cell, comprising:
(a) transfecting the expression vector of claim 7 into a suitable host cell;
and, (b) culturing the host cells of step (a) under conditions which allow expression of said NHL protein from said expression vector.

10. A purified DNA molecule which comprises the nucleotide sequence as set forth in SEQ ID NO:1.

11. An expression vector for expressing a NHL protein in a recombinant host cell wherein said expression vector comprises a DNA molecule of claim 10.

12. A host cell which expresses a recombinant NHL protein wherein said host cell contains the expression vector of claim 11.

13. A purified DNA molecule which consists of the nucleotide sequence as set forth in SEQ ID NO:1.

14. An expression vector for expressing a NHL protein in a recombinant host cell wherein said expression vector comprises a DNA molecule of claim 13.

15. A host cell which expresses a recombinant NHL protein wherein said host cell contains the expression vector of claim 14.

16. A purified DNA molecule of claim 13 which consists of the nucleotide sequence from about nucleotide 828 to about nucleotide 4587, as set forth in SEQ ID
NO:1.

17. An expression vector for expressing a NHL protein in a recombinant host cell wherein said expression vector comprises a DNA molecule of claim 16.

18. A host cell which expresses a recombinant NHL protein wherein said host cell contains the expression vector of claim 17.

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

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

21. A substantially purified NHL protein which comprises the amino acid sequence as set forth in SEQ ID NO:2, wherein said protein is a product of a DNA
expression vector comprising SEQ ID NO:1 and contained within a recombinant host cell.

22. A method of identifying modulators of NHL activity, comprising:
(a) combining a test compound with a NHL protein, wherein NHL comprises the amino acid sequence as set forth in SEQ ID NO:2; and, (b) measuring the effect of the test compound on the NHL protein.

23. An isolated DNA molecule which comprises the nucleotide sequence as set forth in SEQ ID NO:3.

24. An isolated DNA molecule of claim 20 which comprises from about nucleotide 47000 to about nucleotide 85500 of SEQ ID NO:3.

25. An isolated DNA molecule of claim 23 which comprises from about nucleotide 47095 to about nucleotide 85316 of SEQ ID NO:3.

26. A substantially purified NHL protein of claim 21 wherein said protein is a product of a DNA expression vector comprising from about nucleotide 828 to nucleotide 4587, as set forth in SEQ ID NO:1, and contained within a recombinant host cell.