LOCUS HUMHBA4 12847 bp DNA linear PRI 10-AUG-2004 DEFINITION Homo sapiens HBAP1 pseudogene, complete cds; and hemoglobin alpha 2 (HBA2) and hemoglobin alpha 1 (HBA1) genes, complete cds. ACCESSION J00153 J00079 J00154 J00155 J00156 K00418 X00168 VERSION J00153.1 GI:183793 KEYWORDS . SEGMENT 4 of 4 SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 22 (bases 10905 to 12847) AUTHORS Gelinas,R. JOURNAL Unpublished REFERENCE 23 (bases 1 to 12847) AUTHORS Marotta,C.A., Forget,B.G., Weissman,S.M., Verma,I.M., McCaffrey,R.P. and Baltimore,D. TITLE Nucleotide sequences of human globin messenger RNA JOURNAL Proc. Natl. Acad. Sci. U.S.A. 71 (6), 2300-2304 (1974) PUBMED 4135409 REFERENCE 24 (bases 1 to 12847) AUTHORS Proudfoot,N.J. and Brownlee,G.G. TITLE 3' non-coding region sequences in eukaryotic messenger RNA JOURNAL Nature 263 (5574), 211-214 (1976) PUBMED 822353 REFERENCE 25 (bases 7457 to 7499) AUTHORS Proudfoot,N.J. and Longley,J.I. TITLE The 3' terminal sequences of human alpha and beta globin messenger RNAs: comparison with rabbit globin messenger RNA JOURNAL Cell 9 (4 Pt 2), 733-746 (1976) PUBMED 1035137 REFERENCE 26 (bases 7388 to 7499) AUTHORS Wilson,J.T., deRiel,J.K., Forget,B.G., Marotta,C.A. and Weissman,S.M. TITLE Nucleotide sequence of 3' untranslated portion of human alpha globin mRNA JOURNAL Nucleic Acids Res. 4 (7), 2353-2368 (1977) PUBMED 909779 REFERENCE 27 (bases 7372 to 7499) AUTHORS Proudfoot,N.J., Gillam,S., Smith,M. and Longley,J.I. TITLE Nucleotide sequence of the 3' terminal third of rabbit alpha-globin messenger RNA: comparison with human alpha-globin messenger RNA JOURNAL Cell 11 (4), 807-818 (1977) PUBMED 70277 REFERENCE 28 (bases 6666 to 6705; 10477 to 10516) AUTHORS Chang,J.C., Temple,G.F., Poon,R., Neumann,K.H. and Kan,Y.W. TITLE The nucleotide sequences of the untranslated 5' regions of human alpha- and beta-globin mRNAs JOURNAL Proc. Natl. Acad. Sci. U.S.A. 74 (11), 5145-5149 (1977) PUBMED 270752 REFERENCE 29 (bases 6666 to 6709; 10477 to 10520) AUTHORS Baralle,F. TITLE Complete nucleotide sequence of the 5' noncoding region of human alpha-and beta-globin mRNA JOURNAL Cell 12 (4), 1085-1095 (1977) PUBMED 597858 REFERENCE 30 (bases 7045 to 7119; 10856 to 10930) AUTHORS Little,P., Curtis,P., Coutelle,C., Van den Berg,J., Dalgleish,R., Malcolm,S., Courtney,M., Westaway,D. and Williamson,R. TITLE Isolation and partial sequence of recombinant plasmids containing human alpha-, beta- and gamma-globin cDNA fragments JOURNAL Nature 273 (5664), 640-643 (1978) PUBMED 318161 REFERENCE 31 (bases 6666 to 7499) AUTHORS Wilson,J.T., Wilson,L.B., Reddy,V.B., Cavallesco,C., Ghosh,P.K., deRiel,J.K., Forget,B.G. and Weissman,S.M. TITLE Nucleotide sequence of the coding portion of human alpha globin messenger RNA JOURNAL J. Biol. Chem. 255 (7), 2807-2815 (1980) PUBMED 6244294 REFERENCE 32 (bases 2801 to 2872) AUTHORS Lauer,J., Shen,C.K. and Maniatis,T. TITLE The chromosomal arrangement of human alpha-like globin genes: sequence homology and alpha-globin gene deletions JOURNAL Cell 20 (1), 119-130 (1980) PUBMED 6446404 REFERENCE 33 (bases 1 to 12847) AUTHORS Orkin,S.H. and Michelson,A. TITLE Partial deletion of the alpha-globin structural gene in human alpha-thalassaemia JOURNAL Nature 286 (5772), 538-540 (1980) PUBMED 7402334 REFERENCE 34 (bases 2362 to 3373) AUTHORS Proudfoot,N.J. and Maniatis,T. TITLE The structure of a human alpha-globin pseudogene and its relationship to alpha-globin gene duplication JOURNAL Cell 21 (2), 537-544 (1980) PUBMED 7407925 REFERENCE 35 (bases 10431 to 11330) AUTHORS Michelson,A.M. and Orkin,S.H. TITLE The 3' untranslated regions of the duplicated human alpha-globin genes are unexpectedly divergent JOURNAL Cell 22 (2 Pt 2), 371-377 (1980) PUBMED 7448866 REFERENCE 36 (bases 6569 to 7709) AUTHORS Liebhaber,S.A., Goossens,M.J. and Kan,Y.W. TITLE Cloning and complete nucleotide sequence of human 5'-alpha-globin gene JOURNAL Proc. Natl. Acad. Sci. U.S.A. 77 (12), 7054-7058 (1980) PUBMED 6452630 REFERENCE 37 (bases 3107 to 3307; 7358 to 7558; 11176 to 11378) AUTHORS Liebhaber,S.A., Goossens,M. and Kan,Y.W. TITLE Homology and concerted evolution at the alpha 1 and alpha 2 loci of human alpha-globin JOURNAL Nature 290 (5801), 26-29 (1981) PUBMED 7010180 REFERENCE 38 (bases 7441 to 7499; 11227 to 11318) AUTHORS Liebhaber,S.A. and Kan,Y.W. TITLE Differentiation of the mRNA transcripts originating from the alpha 1- and alpha 2-globin loci in normals and alpha-thalassemics JOURNAL J. Clin. Invest. 68 (2), 439-446 (1981) PUBMED 6894931 REFERENCE 39 (bases 6666 to 7499) AUTHORS Orkin,S.H., Goff,S.C. and Hechtman,R.L. TITLE Mutation in an intervening sequence splice junction in man JOURNAL Proc. Natl. Acad. Sci. U.S.A. 78 (8), 5041-5045 (1981) PUBMED 6946451 REFERENCE 40 (bases 12347 to 12847) AUTHORS Shen,C.K. and Maniatis,T. TITLE The organization, structure, and in vitro transcription of Alu family RNA polymerase III transcription units in the human alpha-like globin gene cluster: precipitation of in vitro transcripts by lupus anti-La antibodies JOURNAL J. Mol. Appl. Genet. 1 (4), 343-360 (1982) PUBMED 6286832 REFERENCE 41 (bases 1 to 12847) AUTHORS Proudfoot,N.J., Gil,A. and Maniatis,T. TITLE The structure of the human zeta-globin gene and a closely linked, nearly identical pseudogene JOURNAL Cell 31 (3 Pt 2), 553-563 (1982) PUBMED 6297773 REFERENCE 42 (bases 4238 to 5945; 8489 to 9756) AUTHORS Hess,J.F., Fox,M., Schmid,C. and Shen,C.K. TITLE Molecular evolution of the human adult alpha-globin-like gene region: insertion and deletion of Alu family repeats and non-Alu DNA sequences JOURNAL Proc. Natl. Acad. Sci. U.S.A. 80 (19), 5970-5974 (1983) PUBMED 6310609 REFERENCE 43 (bases 1 to 2749) AUTHORS Sawada,I., Beal,M.P., Shen,C.K., Chapman,B., Wilson,A.C. and Schmid,C. TITLE Intergenic DNA sequences flanking the pseudo alpha globin genes of human and chimpanzee JOURNAL Nucleic Acids Res. 11 (22), 8087-8101 (1983) PUBMED 6316284 REFERENCE 44 (bases 5757 to 7558; 9570 to 11373) AUTHORS Michelson,A.M. and Orkin,S.H. TITLE Boundaries of gene conversion within the duplicated human alpha-globin genes. Concerted evolution by segmental recombination JOURNAL J. Biol. Chem. 258 (24), 15245-15254 (1983) PUBMED 6317690 REFERENCE 45 (bases 4238 to 5945; 8489 to 9756) AUTHORS Hess,J.F., Fox,M.F., Schmid,C. and Shen,C.-K.J. TITLE Molecular evolution of the human adult alpha-globin-like gene region: Insertion and deletion of Alu family repeats and non-Alu DNA sequences JOURNAL Proc. Natl. Acad. Sci. U.S.A. 81, 5892-5892 (1984) REFERENCE 46 (sites) AUTHORS Perez-Stable,C., Ayres,T.M. and Shen,C.K. TITLE Distinctive sequence organization and functional programming of an Alu repeat promoter JOURNAL Proc. Natl. Acad. Sci. U.S.A. 81 (17), 5291-5295 (1984) PUBMED 6089189 REFERENCE 47 (bases 3250 to 4589; 7501 to 8840) AUTHORS Hess,J.F., Schmid,C.W. and Shen,C.K. TITLE A gradient of sequence divergence in the human adult alpha-globin duplication units JOURNAL Science 226 (4670), 67-70 (1984) PUBMED 6474190 REFERENCE 48 (sites) AUTHORS Hess,J., Perez-Stable,C., Wu,G.J., Weir,B., Tinoco,I. Jr. and Shen,C.K. TITLE End-to-end transcription of an Alu family repeat. A new type of polymerase-III-dependent terminator and its evolutionary implication JOURNAL J. Mol. Biol. 184 (1), 7-21 (1985) PUBMED 2411938 REFERENCE 49 (bases 1 to 12847) AUTHORS Fougerousse,F., Meloni,R., Roudaut,C. and Beckmann,J.S. TITLE Dinucleotide repeat polymorphism at the human hemoglobin alpha-1 pseudo-gene (HBAP1) JOURNAL Nucleic Acids Res. 20 (5), 1165 (1992) PUBMED 1549498 COMMENT On Aug 10, 2004 this sequence version replaced gi:31751. [1] sites. [3] sites. [13] sites. [23] sites. [24] revised [21]. [26] sites; Alu repeat 3' to alpha-1 gene. The human alpha globin gene cluster located on chromosome 16 spans about 30 kb and includes the following five loci: 5'- zeta - pseudozeta - pseudoalpha-1 - alpha-2 - alpha-1 -3' [9] This segment of the region, 5'-pseudoalpha-1 -alpha-2 -alpha-1-3', has been compiled from DNA sequencing work as follows: bases 1 to 2749, [20]; 2750 to 3373, [10]; 3374 to 4589, [25]; 4590 to 5756, [21]; 5757 to 7558, [19]; 7559 to 8840, [25]; 8841 to 9569, [21]; 9570 to 11373, [19]; 11374 to 12847, [22]. Only these references and others representing DNA sequencing have been annotated below with regard to base differences; early work with mRNA and cDNA is in some cases ambiguous given that the alpha-2 and alpha-1 coding sequences are identical. It is now known that these genes do differ slightly over the 5' untranslated regions and the intervening sequences, but differ significantly over the 3' untranslated regions. Two alpha chains plus two beta chains (see separate entry) constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin; alpha chains combine with delta chains to constitute HbA-2, which with HbF (fetal hemoglobin) makes up the remaining 3% of adult hemoglobin. Alpha thalassemias result from deletions of each of the alpha genes as well as deletions of both (type 2 and type 1 respectively); some nondeletion alpha thalassemias have also been reported. The pseudoalpha-1 gene is a pseudogene for apparently several reasons: an initiator codon mutation; frameshift deletions; altered splicing sequences which would probably disallow processing of the transcript [10]. The promoter region sequences 'ccaat' and 'ata' found at bases 2387 and 2409 for phba1; at 6595 and 6638 for hba2; and at 10406 and 10448 for hba1 are characteristic of alpha and beta globin genes, as well as of some other mammalian genes, and are thought to influence transcription and translation. The Alu family sequences found throughout this cluster and the beta gene cluster on chromosome 11 are of considerable interest with regard to regulation, recombination and transcription by RNA polymerase III. The Alu unit 3' to the alpha-1 gene has been studied in greatest detail thus far: RNA transcripts generated in vitro by Pol III start at about base 12469 and span 410, 260, 160 and 86 nucleotides [18]. Two promoter elements are postulated for this transcription: an' enhancing element' located at base 12472 and a 'directing element' at base 12538 (both of which are 'intragenic') [23]. Reference [15] missing data project. Kindly being reviewed by Dr. C.-K.J. Shen, University of California, Davis. Complete source information: Human (normal and thalassemic), cDNA to mRNA [2]-[8],[12], and DNA [14]-[11],[15-22],[24]. FEATURES Location/Qualifiers source 1..12847 /organism="Homo sapiens" /mol_type="genomic DNA" /db_xref="taxon:9606" /chromosome="16" /map="16p13.3" repeat_region complement(1729..1741) /note="flanking Alu family repeat [20]" /rpt_type=direct repeat_region complement(1736..2059) /note="[20]" /rpt_family="Alu" /rpt_type=dispersed repeat_region complement(2073..2085) /note="flanking Alu family repeat [20]" /rpt_type=direct misc_difference 2362 /citation=[13] /replace="" misc_difference 2368..2372 /citation=[13] /replace="" gene 2436..3248 /gene="HBAP1" /pseudo exon 2436..2569 /gene="HBAP1" /number=1 /pseudo misc_difference 2449..2451 /gene="HBAP1" /citation=[13] /replace="" misc_difference 2465..2467 /gene="HBAP1" /citation=[13] /replace="" CDS join(2475..2569,2697..2881,3016..3137) /gene="HBAP1" /pseudo /codon_start=1 intron 2570..2696 /gene="HBAP1" /note="[10],[11],[19] (no splice consensus at 2570); putative; does not fit consensus" /number=1 /pseudo exon 2697..2881 /gene="HBAP1" /note="pseudo-hba1, [10]" /number=2 /pseudo old_sequence 2831 /gene="HBAP1" /citation=[11] intron 2882..3015 /gene="HBAP1" /note="[10],[11],[19] (no splice consensus at 2882); putative; does not fit consensus" /number=2 /pseudo exon 3016..3248 /gene="HBAP1" /number=3 /pseudo misc_difference 3155..3161 /gene="HBAP1" /citation=[16] /replace="" misc_difference 3187 /gene="HBAP1" /citation=[16] /replace="" misc_difference 3203 /gene="HBAP1" /citation=[16] /replace="" misc_difference 3209..3211 /gene="HBAP1" /citation=[16] /replace="" misc_difference 3233..3234 /gene="HBAP1" /citation=[16] /replace="" misc_difference 3246 /gene="HBAP1" /citation=[16] /replace="" old_sequence 4246..4248 /citation=[21] repeat_region 4281..4295 /note="flanking Alu family repeat [21]" /rpt_type=direct old_sequence 4282..4284 /citation=[21] repeat_region 4301..4582 /note="[21]" /rpt_family="Alu" /rpt_type=dispersed old_sequence 4441..4444 /citation=[21] old_sequence 4509 /citation=[21] old_sequence 4525 /citation=[21] old_sequence 4553..4555 /citation=[21] repeat_region 4601..4615 /note="flanking Alu family repeat [21]" /rpt_type=direct repeat_region complement(4992..5004) /note="flanking Alu family repeat [21]" /rpt_type=direct repeat_region complement(4993..5616) /note="[21]" /rpt_family="Alu" /rpt_type=dispersed repeat_region complement(5629..5641) /note="flanking Alu family repeat [21]" /rpt_type=direct misc_difference 5778..5781 /citation=[24] /replace="" old_sequence 5938..5940 /citation=[21] gene 6666..7499 /gene="HBA2" mRNA join(6666..6797,6915..7119,7262..7499) /gene="HBA2" /product="hemoglobin alpha 2" CDS join(6703..6797,6915..7119,7262..7390) /gene="HBA2" /codon_start=1 /product="hemoglobin alpha 2" /protein_id="AAB59407.1" /db_xref="GI:386764" /translation="MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYF PHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLL SHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR" variation 6798..6804 /gene="HBA2" /note="gtgaggc in normal; gc in thalassemia mutation [17]" /replace="gc" variation 7388 /gene="HBA2" /note="t in normal Hb, c in Hb Constant Spring [4],[6]" /replace="c" polyA_signal 7479..7484 /gene="HBA2" /note="[3],[14]" old_sequence 8492 /citation=[21] repeat_region 8532..8546 /note="Alu flanking repeat" /rpt_type=direct repeat_region 8552..8800 /note="3' end uncertain; [18], [21]" /rpt_family="Alu" /rpt_type=dispersed old_sequence 9069 /citation=[21] old_sequence 9700 /citation=[21] old_sequence 9749..9751 /citation=[21] gene 10477..11318 /gene="HBA1" mRNA join(10477..10608,10726..10930,11080..11318) /gene="HBA1" /product="hemoglobin alpha 1" CDS join(10514..10608,10726..10930,11080..11208) /gene="HBA1" /codon_start=1 /product="hemoglobin alpha 1" /protein_id="AAB59408.1" /db_xref="GI:386765" /translation="MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYF PHFDLSHGSAQVKGHGKKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLL SHCLLVTLAAHLPAEFTPAVHASLDKFLASVSTVLTSKYR" variation 10802 /gene="HBA1" /note="HBA1 deletion leading to thalassemia [11],[13]" polyA_signal 11298..11303 /gene="HBA1" /note="[11]" repeat_region 12469..12729 /note="[18]" /rpt_family="Alu" /rpt_type=dispersed misc_difference 12531 /citation=[19] /replace="" misc_difference 12573..12575 /citation=[19] /replace="" misc_difference 12782..12783 /citation=[19] /replace="" misc_difference 12839..12841 /citation=[19] /replace="" ORIGIN 1 ggatccccgg ggctctgggc ggtgtgggcg tagtgaagcc ccacgcagcc gccctcctcc 61 ccggtcactg actggtcctg caggctcttc acggtgtacc ccagcaccaa ggtctacttc 121 ccgcacctga gcgcctgcca ggacgacgca gctgctgagc cacgggagcg catctgcggc 181 tgtggcgcgg cggtgcagca cgtggacaac ctgcgcgcct gagcccgctg gcggacctga 241 cgctcgttgc gcgtggaccc agccaacttt ccggtgaggc ctttccggcc ggggcaatgg 301 tgcatcgcct agccgggatg ggggggctct gggggtccct agcggggcag accccgtctc 361 accggcccct tctcctgcag ctgctaatcc agtgtttcca cgtcgtgctg gcctcccacc 421 tgcaggacga gttcaccgtg caaatgcaag cggcgtggga caagttcctg actggtgtgg 481 ccgtggtgct gaccgaaaaa tacgctgagc cctgtgctgc gaggccttgg tctgtgcatg 541 tcaataaaca gaggcccgaa ccatctgccc ctgcctgtgt ggtctttggg gagctagcaa 601 agcgaggtca ctattgttgg ccagtaagct cagggaccta aagggagcct cctagaactc 661 tcaaatgcgc cccacccccg gaggtttgtc ctcccatggc gaggagtgcg atggggcaga 721 gggagcagtg tgatatggcg ggggtagaga gggtggcctt cgacttcaaa cccttgactc 781 gggcttcgaa ccatactcgt tcgcaaagca gttccccatt catgcattta ttcagttcat 841 tccttccctc catccccatt tcctgctggg acctgtagat gctaatcctg gccctttttg 901 cagagagatg cagaaactga ggtcccagag ccaaatgtgc aacctaattc gttggccaga 961 gcagagggcc gcagacctgt tcctttcccc ttccttcccc catggacact tcctcagtgg 1021 caaacctgcg ctagcctggt tagccctccc tgtgaccctg cagccctggg gatgaggtcg 1081 ggaggaagac ctcagtggcc acaatttggc agacagagag gtttagtctt ccagcctgct 1141 caatgacaag ctgtgcgacc ctgggctgtc ccagagctct aggcctttac ctatcgaata 1201 gaaaaacagc gtccaactca tgagattttt gaaataattt ttgaaatcat aacacagggt 1261 gggtgcctgc agggacgttg ccaccccacc cctccaccca gccccagctg ccgtgtctca 1321 atctctgcag gtgcccaggc caaggcattc ccttccccag gctccctctt ctccctcccc 1381 aaggattggg aagggaatct tagggctcca ccccaggctt ttcagacaaa gaataggggc 1441 tcaggaaaga ttgggacctt ggagttctcc aatccctaat agggttgggt gtgggttggg 1501 catcctgggt gtgtgtgggg agcacctgga ccaggcctgg cacccaggtc tgacctggca 1561 gtcagcaatg aggtctgaag agagctgctg gaagtggagc cctgactgtg agtcggccaa 1621 actcccccca gcagtcagtg ccacagacct gttgccctgc actgcctggg accccagccc 1681 ggtagtttgg agaacttggc ccctcgttat ctacatcccc caagtgtttt tttgtttttg 1741 ggggtttttt tttttttttt tttgctttgt ttttgttttt gagataggcc cttgctctga 1801 caccccggct ggagtgcagt ggcaagtttt ggctcactgc agcctcaacc tcctgggttc 1861 aagcgattct cctgcctctg tctcccgtgt agctgggatt acaggcatgg gccgccattc 1921 ctggctaatt tatgtatttt taatagagac acagtttcac catgttgatc aggctggtct 1981 caaactcctg acctcaagtg atctgccctc ctggtctccc aaagtgctgg gatgacaggc 2041 gtgagccacc acacccagcc cccgcaactg tttacatgga taattaacaa gctttttgtc 2101 ccaggcagag tttggtgtga aagcagctta tgtttcactt tggaaaaact gtgctcttct 2161 ccccatccag gaagctgcct gggtctgggc catatgtgga taccttatgg gtataagctg 2221 ctcaggaccc tgtgtggaag ctcaggacaa tgccagcggg aaggctacca tgtggagagc 2281 tgtctctgtt tgggcaggac taagagacgc agggaacctt gggaacctgt ctactctcac 2341 tcactcctcc tcccctttcc ttccaggcac ctctgcaact tgccagccaa tgaccctgca 2401 tcccaggcat aagagctcct actctccccc acctttcact tttgagctta cacagactca 2461 gaaattaagc tgccgtggtg ctgtctcctg aggacaaggc taacaccaag gcggtctggg 2521 agaaagttgg cgaccacact gctggctatg ccacggaggc cctggagagg caagaaccct 2581 cctctccctg ctcacacctt gggtccaacg cccactccag ggctccactg gccaccccta 2641 actattctta ccctggaccc agcccccagc ccctcactct ttgcttcccc ctgaagcatg 2701 ttcctgacct tcctctcact tggccctgag ttatggctca gcccagatca agaaacaatg 2761 caagtaggtg gccgacacgc tgaccaatgc cgtggtccac ttagatgaca tgcccaatga 2821 tgtgtctgag gtgaggaagc tgcatgtcca cgagctgtgg gtggacccag gcaacatcag 2881 ggagagcttt gggctgggag gaatctaggg tgtgggggca gctggccttc ctcataggac 2941 agaccctccc acgcgttcag ggaggtggag cacaggtggc agtagtatct gcatcccctg 3001 actctctctc cacagttcct gggtaaatgc ctgctggtga cctaggcctg ccacaccctt 3061 cccggtttac ccatgtggtg cctccatgga caaattattt gcttttgtga gtgctgtgtt 3121 gacctaaaaa caccattaag ctagagcatt ggtggtcatg ccccctgcct gctgggcctc 3181 ccaccaggcc cgcctcccct ccctgcccca gcacttcctg atctttgaat gaagtccgag 3241 taggcagcag cctgtgtgtg cctgggttct ctctgtcccg gaatgtgcca acagtggagg 3301 tgtttacctg tctcagacca aggacctctc tgcagctgca tggggctggg gagggagaac 3361 tgcagggagt atgggagggg aagctgaggt gggcctgctc aagagaaggt gctgaaccat 3421 cccctgtcct gagaggtgcc aggcctgcag gcagtggctc agaagctggg gaggagagag 3481 gcatccaggg ttctactcag ggagtcccag catcgccacc ctcctttgaa atctccctgg 3541 ttgaacccag ttaacatacg ctctccatca aaacaaaacg aaacaaaaca aactagcaaa 3601 ataggctgtc cccagtgcaa gtgcaggtgc cagaacattt ctctcattcc caccccttcc 3661 tgccagaggg taggtggctg gagtgagggt gctggcccta ctcacacttc ctgtgtcatg 3721 gtgaccctct gagagcagcc cagtcagtgg ggaaggagga aggggctggg atgctcacag 3781 ccggcagccc acacctaggg agactcttca gcagagcacc ttgcggcctt actcctgcac 3841 gtctcctgca gtttgtaagg tgcattcaga actcactgtg tgcccagccc tgagctccca 3901 gctaattgcc ccacccaggg cctctgggac ctcctggtgc ttctgcttcc tgtgctgcca 3961 gcaacttctg gaaacgtccc tgtccccggt gctgaagtcc tggaatccat gctgggaagt 4021 tgcacagccc atctggctct cagccagcct aggaacacga gcagcacttc cagcccagcc 4081 cctgccccac agcaagcctc cccctccaca ctcacagtac tgaattgagc tttgggtagg 4141 gtggagagga ccctgtcacc gcttttcttc tggacatgga cctctctgaa ttgttgggga 4201 gttccctccc cctctccacc acccactctt cctgtgcctc acagcccaga gcattgttat 4261 ttcaacagaa acactttaaa aaataaacta aaatccgaca ggcacggtgg ctcacacctg 4321 taatcccagt actttgggag gctgaggcga gaggatcacc tgaggtcggg agtttgagac 4381 cagcctgacc aatatggaga aaccccagtt atactaaaaa tacaaaatta gctgggtgtg 4441 gtggcgcatg cctgtaatcc tagctactag gaaggctgag gcaggagaat cgcttgaacc 4501 cgggaggtgg aggttgaggt gagccgagat cacgccattg cactccagcc tgggcaacaa 4561 gagcaaaact ccgtctcaaa aaataaataa ataaataaat aaataaacta aaatctatcc 4621 atgctttcac acacacacac acacacacac acacacacct tttttgtgtt actaaagtag 4681 gagagtgtct ctctttcctg tctcctcaca cccaccccca gaagagacca aaatgaaggg 4741 tttggaactc acgccatggg ccccatccca tgctgaggga acacagctac atctacaact 4801 actgccacag cgtctctttt tggacacccc taccatcata ctgtagatac ccgtgtacaa 4861 ccttcctatt ctcagtgaag tgtctcccct gcatcccttt cagccagttc attcagctct 4921 gctcgcccat tccacagtct cactgattat tactatgttt ccatcatgat ccccccaaaa 4981 aatcatgact ttattttttt atttttatta ttattattat tttttttttt ttttttgaga 5041 cggagtctcg ctctgtgacc caggctggag tgcagtggca aatctcggct cactgcaagc 5101 tccacctcgc aggttcacgc cattctcctc cctcagcctc ccgagtcgct gagtagctgg 5161 gctacagcgc cccccactag tcgtggctaa ttttttcttt ttttaataga gacagagttt 5221 cactgcatta gcgaggatgg tctcgatctc ctgacctcgc atctgccagc ctcagccttc 5281 caatgtgctg ggattacagc gtgagccaac gcgcccggcc ttatatattt atttttttga 5341 gacagagtct cgctgtgtcg tcaggctaga gtgctgtggc acgatctcgg ctcactgcaa 5401 cctccaactc cctggttcaa aggattctcc agcctccacc tcccgagtag ctgggattac 5461 aggcgtgcac caccacacca gctaattttt gtatttttag tagagacggg gtttctccat 5521 gttggtcagc ctggtctcga actcccgacc acagctgatc ccacccacct cggcctccca 5581 aagtgctggg attccaggcg tgcgccgagc ctggccaaac catcactttt catgagcagg 5641 gatgcaccca ctggactcct ggacctccca ccctccccct cgccaagtcc accccttcct 5701 tcctcacccc acatcccctc acctacattc tgcaacacag gggccttctc tcccctgtcc 5761 tttccctacc cagagccagg tttgtttatc tgtttacaac cagtatttac ctagcaagtc 5821 ttccatcaga tagcatttgg agagctgggg gtgtcacagt gaaccacgac ctctaggcca 5881 gtgggagagt cagtcacaca aactgtgagt ccatgacttg gggcttagcc agtacccacc 5941 accccacgcg ccaccccaca accccgggta gaggagtctg aatctggagc cgcccccagc 6001 ccagccccgt gctttttgcg tcctggtgtt tgttccttcc cggtgcctgt cactcaagca 6061 cactagtgac tatcgccaga gggaaaggga gctgcaggaa gcgaggctgg agagcaggag 6121 gggctctgcg cagaaattct tttgagttcc tatgggccag ggcgtccggg tgcgcgcatt 6181 cctctccgcc ccaggattgg gcgaagccct ccggctcgca ctcgctcgcc cgtgtgttcc 6241 ccgatcccgc tggagtcgat gcgcgtccag cgcgtgccag gccggggcgg gggtgcgggc 6301 tgactttctc cctcgctagg gacgctccgg cgcccgaaag gaaagggtgg cgctgcgctc 6361 cggggtgcac gagccgacag cgcccgaccc caacgggccg gccccgccag cgccgctacc 6421 gccctgcccg ggcgagcggg atgggcggga gtggagtggc gggtggaggg tggagacgtc 6481 ctggcccccg ccccgcgtgc acccccaggg gaggccgagc ccgccgcccg gccccgcgca 6541 ggccccgccc gggactcccc tgcggtccag gccgcgcccc gggctccgcg ccagccaatg 6601 agcgccgccc ggccgggcgt gcccccgcgc cccaagcata aaccctggcg cgctcgcggc 6661 ccggcactct tctggtcccc acagactcag agagaaccca ccatggtgct gtctcctgcc 6721 gacaagacca acgtcaaggc cgcctggggt aaggtcggcg cgcacgctgg cgagtatggt 6781 gcggaggccc tggagaggtg aggctccctc ccctgctccg acccgggctc ctcgcccgcc 6841 cggacccaca ggccaccctc aaccgtcctg gccccggacc caaaccccac ccctcactct 6901 gcttctcccc gcaggatgtt cctgtccttc cccaccacca agacctactt cccgcacttc 6961 gacctgagcc acggctctgc ccaggttaag ggccacggca agaaggtggc cgacgccctg 7021 accaacgccg tggcgcacgt ggacgacatg cccaacgcgc tgtccgccct gagcgacctg 7081 cacgcgcaca agcttcgggt ggacccggtc aacttcaagg tgagcggcgg gccgggagcg 7141 atctgggtcg aggggcgaga tggcgccttc ctctcagggc agaggatcac gcgggttgcg 7201 ggaggtgtag cgcaggcggc ggctgcgggc ctgggccgca ctgaccctct tctctgcaca 7261 gctcctaagc cactgcctgc tggtgaccct ggccgcccac ctccccgccg agttcacccc 7321 tgcggtgcac gcctccctgg acaagttcct ggcttctgtg agcaccgtgc tgacctccaa 7381 ataccgttaa gctggagcct cggtagccgt tcctcctgcc cgatgggcct cccaacgggc 7441 cctcctcccc tccttgcacc ggcccttcct ggtctttgaa taaagtctga gtgggcggca 7501 gcctgtgtgt gcctgggttc tctctgtccc ggaatgtgcc aacaatggag gtgtttacct 7561 gtctcagacc aaggacctct ctgcagctgc atggggctgg ggagggagaa ctgcagggag 7621 tatgggaggg gaagctgagg tgggcctgct caagagaagg tgctgaacca tcccctgtcc 7681 tgagaggtgc caggcctgca ggcagtggct cagaagctgg ggaggagaga ggcatccagg 7741 gttctactca gggagtccca gcatcgccac cctcctttga aatctccctg gttgaaccca 7801 gttaacatac gctctccatc aaaacaaaac gaaacaaaac aaactagcaa aataggctgt 7861 ccccagtgca agtgcaggtg ccagaacatt tctctcattc ccaccccttc ctgccagagg 7921 gtaggtggct ggagtgaggg tgctggccct actcacactt cctgtgtcac ggtgaccctc 7981 tgagagcagc ccagtcagtg gggaaggagg aaggggctgg gatgctcaca gccggcagcc 8041 cacacctagg gagactcttc agcagagcac cttgcggcct tactcctgca cgtctcctgc 8101 agtttgtaag gtgcattcag aactcactgt gtgcccagcc ctgagctccc agctaattgc 8161 cccacccagg gcctctggga cctcctggtg cttctgcttc ctgtgctgcc agcaacttct 8221 ggaaacgtcc ctgtccccgg tgctgaagtc ctggaatcca tgctgggaag ttgcacagcc 8281 catctggctc tcagccagcc taggaacatg agcagcactt ccaacccagt ccctgcccca 8341 cagcaagcct ccccctccac actcacagta ctggattgag ctttggggag ggtggagagg 8401 accctgtcac cgctttcctt ctggacatgg acctctctga attgttgggg agttccctcc 8461 ccctctccac cacccgctct tcctgcgcct cacagcccag agcattgtta tttcagcaga 8521 aacactttaa aaaataaact aaaatccgac aggcacggtg gctcacgcct gtaatcccag 8581 cactttggga ggccgaggtg ggaggatcac ctgaggtcgg gagtttgaga ccaccctgat 8641 caacatgtag aaaccccatc tatactaaaa atacaaaatc agccgggcat ggtggcccat 8701 gcctgtaaac ccacctactc cggaggctga ggcaggagaa tcattttaac caaggaggca 8761 gaggttgcag tgagctaaga tcacaccatt gcactccagc ctggaaaaca acagcgaaac 8821 tccgcctcaa aaaaaaaaaa gcccccacat cttatctttt ttttttcctt caggctgtgg 8881 gcagagtcag aaagtcagaa gagggtggca gacagggagg ggaaatgaga agatccaacg 8941 ggggaagcat tgctaagctg gtcggagcta cttccttctc tgcccaaggc agcttaccct 9001 ggcttgctcc tggacaccca gggcagggcc tgagtaaggg cctggggaga cagggcaggg 9061 agcaggctga agggtgctga cctgatgcac tcctcaaagc agatcttctg ccagaccccc 9121 aggaaatgac ttatcagtga tttctcaggc tgttttctcc tcagtaccat ccccccaaaa 9181 aacatcactt ttcatgcaca gggatgcacc cactggcact cctgcacctc ccacccttcc 9241 ccagaagtcc accccttcct tcctcaccct gcaggagctg gccagcctca tcaccccaac 9301 atctccccac ctccattctc caaccacagg gcccttgtct cctctgtcct ttcccctccc 9361 cgagccaagc ctcctccctc ctccacctcc tccacctaat acatatcctt aagtctcacc 9421 tcctccagga agccctcaga ctaaccctgg tccccttgaa tgcctcgtcc acacctccag 9481 acttcctcag ggcctgtgat gaggtctgca cctctgtgtg tacttgtgtg atggttagag 9541 gactgcctac ctcccagagg aggttgaatg ctccagccgg ttccagctat tgctttgttt 9601 acctgtttaa ccagtattta cctagcaagt cttccatcag atagcatttg gagagctggg 9661 ggtgtcacag tgaaccacga cctctaggcc agtgggagag tcagtcacac aaactgtgag 9721 tccatgactt ggggcttagc cagcacccac caccccacgc gccaccccac aaccccgggt 9781 agaggagtct gaatctggag ccgcccccag cccagccccg tgctttttgc gtcctggtgt 9841 ttattccttc ccggtgcctg tcactcaagc acactagtga ctatcgccag agggaaaggg 9901 agctgcagga agcgaggctg gagagcagga ggggctctgc gcagaaattc ttttgagttc 9961 ctatgggcca gggcgtccgg gtgcgcgcat tcctctccgc cccaggattg ggcgaagccc 10021 tccggctcgc actcgctcgc ccgtgtgttc cccgatcccg ctggagtcga tgcgcgtcca 10081 gcgcgtgcca ggccggggcg ggggtgcggg ctgactttct ccctcgctag ggacgctccg 10141 gcgcccgaaa ggaaagggtg gcgctgcgct ccggggtgca cgagccgaca gcgcccgacc 10201 ccaacgggcc ggccccgcca gcgccgctac cgccctgccc gggcgagcgg gatgggcggg 10261 agtggagtgg cgggtggagg gtggagacgt cctggccccc gccccgcgtg cacccccagg 10321 ggaggccgag cccgccgccc ggccccgcgc aggccccgcc cgggactccc ctgcggtcca 10381 ggccgcgccc cgggctccgc gccagccaat gagcgccgcc cggccgggcg tgcccccgcg 10441 ccccaagcat aaaccctggc gcgctcgcgg cccggcactc ttctggtccc cacagactca 10501 gagagaaccc accatggtgc tgtctcctgc cgacaagacc aacgtcaagg ccgcctgggg 10561 taaggtcggc gcgcacgctg gcgagtatgg tgcggaggcc ctggagaggt gaggctccct 10621 cccctgctcc gacccgggct cctcgcccgc ccggacccac aggccaccct caaccgtcct 10681 ggccccggac ccaaacccca cccctcactc tgcttctccc cgcaggatgt tcctgtcctt 10741 ccccaccacc aagacctact tcccgcactt cgacctgagc cacggctctg cccaggttaa 10801 gggccacggc aagaaggtgg ccgacgccct gaccaacgcc gtggcgcacg tggacgacat 10861 gcccaacgcg ctgtccgccc tgagcgacct gcacgcgcac aagcttcggg tggacccggt 10921 caacttcaag gtgagcggcg ggccgggagc gatctgggtc gaggggcgag atggcgcctt 10981 cctcgcaggg cagaggatca cgcgggttgc gggaggtgta gcgcaggcgg cggctgcggg 11041 cctgggccct cggccccact gaccctcttc tctgcacagc tcctaagcca ctgcctgctg 11101 gtgaccctgg ccgcccacct ccccgccgag ttcacccctg cggtgcacgc ctccctggac 11161 aagttcctgg cttctgtgag caccgtgctg acctccaaat accgttaagc tggagcctcg 11221 gtggccatgc ttcttgcccc ttgggcctcc ccccagcccc tcctcccctt cctgcacccg 11281 tacccccgtg gtctttgaat aaagtctgag tgggcggcag cctgtgtgtg cctgagtttt 11341 ttccctcaga aacgtgccag catgggcgtg gacagcagct gggacacaca tggctagaac 11401 ctctctgcag ctggataggg taggaaaagg caggggcggg aggaggggat ggaggaggga 11461 aagtggagcc accgcgaagt ccagctggaa aaacgctgga ccctagagtg ctttgaggat 11521 gcatttgctc tttcccgagt tttattccca gacttttcag attcaatgca ggtttgctga 11581 aataatgaat ttatccatct ttacgtttct gggcactctt gtgccaagaa ctggctggct 11641 ttctgcctgg gacgtcactg gtttcccaga ggtcctccca catatgggtg gtgggtaggt 11701 cagagaagtc ccactccagc atggctgcat tgatccccca tcgttcccac tagtctccgt 11761 aaaacctccc agatacaggc acagtctaga tgaaatcagg ggtgcggggt gcaactgcag 11821 gccccaggca attcaatagg ggctctactt tcacccccag gtcaccccag aatgctcaca 11881 caccagacac tgacgccctg gggctgtcaa gatcaggcgt ttgtctctgg gcccagctca 11941 gggcccagct cagcacccac tcagctcccc tgaggctggg gagcctgtcc cattgcgact 12001 ggagaggaga gcggggccac agaggcctgg ctagaaggtc ccttctccct ggtgtgtgtt 12061 ttctctctgc tgagcaggct tgcagtgcct ggggtatcag agggagggtt cccggagctg 12121 gtagccataa agccctggcc ctcaactgat aggaatatct tttattccct gagcccatga 12181 atcacccttg gtaaacacct atggcaggcc ctctgcctgc gtttgtgatg tccttcccgc 12241 agcctgtggg tacagtatca actgtcagga agacggtgtc ttcgttattt catcaggaag 12301 aatggaggtc tgacctaaag gtagaaatat gtcaaatgta cagcagaggg ctggttggag 12361 tgcagcgctt tttacaatta attgatcaga accagttata aatttatcat ttccttctcc 12421 actcctgctg cttcagttga ctaagcctaa gaaaaaatta taaaaattgg ccgggcgcgg 12481 tggctcacac ctgtaattgc agcactttgc caggcttagg caggtggatc acctgaagtc 12541 aggggttcga gaccagccta gccaacatag tgaaaccctg tctctactaa aaagacaaaa 12601 attgtccagg tgtgatgact catgcctgta aacctggcac tttgggaggc ggaggttgta 12661 gtgagtcaag atcgcgccat cgcactccag cttgggcaac aagagcgaaa ctctgtctca 12721 aaaaaaaatt taatctaatt taatttaatt taaaaattag cacggtggtt gggcacagtg 12781 gcctcacgcc tgtaatccca gcactttggg aagccaaggt gggcagatca caaggtcagg 12841 ggaattc //