LOCUS       NM_001407894            7057 bp    mRNA    linear   PRI 05-OCT-2024
DEFINITION  Homo sapiens BRCA1 DNA repair associated (BRCA1), transcript
            variant 168, mRNA.
ACCESSION   NM_001407894
VERSION     NM_001407894.1
KEYWORDS    RefSeq.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 7057)
  AUTHORS   Orban,T.I. and Olah,E.
  TITLE     Emerging roles of BRCA1 alternative splicing
  JOURNAL   Mol Pathol 56 (4), 191-197 (2003)
   PUBMED   12890739
  REMARK    Review article
REFERENCE   2  (bases 1 to 7057)
  AUTHORS   Orban,T.I. and Olah,E.
  TITLE     Expression profiles of BRCA1 splice variants in asynchronous and in
            G1/S synchronized tumor cell lines
  JOURNAL   Biochem Biophys Res Commun 280 (1), 32-38 (2001)
   PUBMED   11162473
REFERENCE   3  (bases 1 to 7057)
  AUTHORS   Paterson,J.W.
  TITLE     BRCA1: a review of structure and putative functions
  JOURNAL   Dis Markers 13 (4), 261-274 (1998)
   PUBMED   9553742
  REMARK    Review article
REFERENCE   4  (bases 1 to 7057)
  AUTHORS   Xu,C.F., Chambers,J.A., Nicolai,H., Brown,M.A., Hujeirat,Y.,
            Mohammed,S., Hodgson,S., Kelsell,D.P., Spurr,N.K., Bishop,D.T. and
            Solomon,E.
  TITLE     Mutations and alternative splicing of the BRCA1 gene in UK
            breast/ovarian cancer families
  JOURNAL   Genes Chromosomes Cancer 18 (2), 102-110 (1997)
   PUBMED   9115959
REFERENCE   5  (bases 1 to 7057)
  AUTHORS   Wilson,C.A., Payton,M.N., Elliott,G.S., Buaas,F.W., Cajulis,E.E.,
            Grosshans,D., Ramos,L., Reese,D.M., Slamon,D.J. and Calzone,F.J.
  TITLE     Differential subcellular localization, expression and biological
            toxicity of BRCA1 and the splice variant BRCA1-delta11b
  JOURNAL   Oncogene 14 (1), 1-16 (1997)
   PUBMED   9010228
REFERENCE   6  (bases 1 to 7057)
  AUTHORS   Thakur,S., Zhang,H.B., Peng,Y., Le,H., Carroll,B., Ward,T., Yao,J.,
            Farid,L.M., Couch,F.J., Wilson,R.B. and Weber,B.L.
  TITLE     Localization of BRCA1 and a splice variant identifies the nuclear
            localization signal
  JOURNAL   Mol Cell Biol 17 (1), 444-452 (1997)
   PUBMED   8972225
REFERENCE   7  (bases 1 to 7057)
  AUTHORS   Lu,M., Conzen,S.D., Cole,C.N. and Arrick,B.A.
  TITLE     Characterization of functional messenger RNA splice variants of
            BRCA1 expressed in nonmalignant and tumor-derived breast cells
  JOURNAL   Cancer Res 56 (20), 4578-4581 (1996)
   PUBMED   8840964
REFERENCE   8  (bases 1 to 7057)
  AUTHORS   Holt,J.T., Thompson,M.E., Szabo,C., Robinson-Benion,C.,
            Arteaga,C.L., King,M.C. and Jensen,R.A.
  TITLE     Growth retardation and tumour inhibition by BRCA1
  JOURNAL   Nat Genet 12 (3), 298-302 (1996)
   PUBMED   8589721
  REMARK    Erratum:[Nat Genet 1998 May;19(1):102]
REFERENCE   9  (bases 1 to 7057)
  AUTHORS   Xu,C.F., Brown,M.A., Chambers,J.A., Griffiths,B., Nicolai,H. and
            Solomon,E.
  TITLE     Distinct transcription start sites generate two forms of BRCA1 mRNA
  JOURNAL   Hum Mol Genet 4 (12), 2259-2264 (1995)
   PUBMED   8634696
REFERENCE   10 (bases 1 to 7057)
  AUTHORS   Miki,Y., Swensen,J., Shattuck-Eidens,D., Futreal,P.A., Harshman,K.,
            Tavtigian,S., Liu,Q., Cochran,C., Bennett,L.M., Ding,W. et al.
  TITLE     A strong candidate for the breast and ovarian cancer susceptibility
            gene BRCA1
  JOURNAL   Science 266 (5182), 66-71 (1994)
   PUBMED   7545954
REFERENCE   11 (bases 1 to 7057)
  AUTHORS   Mehta,P.A. and Ebens,C.
  TITLE     Fanconi Anemia
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301575
REFERENCE   12 (bases 1 to 7057)
  AUTHORS   Petrucelli,N., Daly,M.B. and Pal,T.
  TITLE     BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301425
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC135721.4.
            
            Summary: This gene encodes a 190 kD nuclear phosphoprotein that
            plays a role in maintaining genomic stability, and it also acts as
            a tumor suppressor. The BRCA1 gene contains 22 exons spanning about
            110 kb of DNA. The encoded protein combines with other tumor
            suppressors, DNA damage sensors, and signal transducers to form a
            large multi-subunit protein complex known as the BRCA1-associated
            genome surveillance complex (BASC). This gene product associates
            with RNA polymerase II, and through the C-terminal domain, also
            interacts with histone deacetylase complexes. This protein thus
            plays a role in transcription, DNA repair of double-stranded
            breaks, and recombination. Mutations in this gene are responsible
            for approximately 40% of inherited breast cancers and more than 80%
            of inherited breast and ovarian cancers. Alternative splicing plays
            a role in modulating the subcellular localization and physiological
            function of this gene. Many alternatively spliced transcript
            variants, some of which are disease-associated mutations, have been
            described for this gene, but the full-length natures of only some
            of these variants has been described. A related pseudogene, which
            is also located on chromosome 17, has been identified. [provided by
            RefSeq, May 2020].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR14038196.1868552.1,
                                           SRR14038191.3617532.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-88                AC135721.4         34056-34143
            89-187              AC135721.4         35305-35403
            188-241             AC135721.4         43641-43694
            242-297             AC135721.4         52887-52942
            298-386             AC135721.4         54464-54552
            387-526             AC135721.4         55159-55298
            527-629             AC135721.4         59543-59645
            630-675             AC135721.4         62131-62176
            676-752             AC135721.4         63498-63574
            753-4178            AC135721.4         64560-67985
            4179-4267           AC135721.4         68388-68476
            4268-4439           AC135721.4         76845-77016
            4440-4566           AC135721.4         82806-82932
            4567-4757           AC135721.4         84899-85089
            4758-5068           AC135721.4         88182-88492
            5069-5156           AC135721.4         91725-91812
            5157-5234           AC135721.4         95469-95546
            5235-5275           AC135721.4         96047-96087
            5276-5359           AC135721.4         102285-102368
            5360-5414           AC135721.4         108303-108357
            5415-5488           AC135721.4         110226-110299
            5489-5549           AC135721.4         111717-111777
            5550-7057           AC135721.4         113618-115125
FEATURES             Location/Qualifiers
     source          1..7057
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17q21.31"
     gene            1..7057
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /note="BRCA1 DNA repair associated"
                     /db_xref="GeneID:672"
                     /db_xref="HGNC:HGNC:1100"
                     /db_xref="MIM:113705"
     exon            1..88
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            89..187
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            188..241
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            242..297
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     CDS             296..5674
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /EC_number="2.3.2.27"
                     /note="isoform 6 is encoded by transcript variant 168;
                     BRCA1/BRCA2-containing complex, subunit 1; RING finger
                     protein 53; breast cancer type 1 susceptibility protein;
                     breast and ovarian cancer susceptibility protein 1;
                     protein phosphatase 1, regulatory subunit 53; Fanconi
                     anemia, complementation group S; early onset breast cancer
                     1; breast cancer 1, early onset"
                     /codon_start=1
                     /product="breast cancer type 1 susceptibility protein
                     isoform 6"
                     /protein_id="NP_001394823.1"
                     /db_xref="GeneID:672"
                     /db_xref="HGNC:HGNC:1100"
                     /db_xref="MIM:113705"
                     /translation="MSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNS
                     PEHLKDEVSIIQSMGYRNRAKRLLQSEPENPSLETSLSVQLSNLGTVRTLRTKQRIQP
                     QKTSVYIELGSDSSEDTVNKATYCSVGDQELLQITPQGTRDEISLDSAKKAACEFSET
                     DVTNTEHHQPSNNDLNTTEKRAAERHPEKYQGSSVSNLHVEPCGTNTHASSLQHENSS
                     LLLTKDRMNVEKAEFCNKSKQPGLARSQHNRWAGSKETCNDRRTPSTEKKVDLNADPL
                     CERKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESES
                     NAKVADVLDVLNEVDEYSGSSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGK
                     TYRKKASLPNLSHVTENLIIGAFVTEPQIIQERPLTNKLKRKRRPTSGLHPEDFIKKA
                     DLAVQKTPEMINQGTNQTEQNGQVMNITNSGHENKTKGDSIQNEKNPNPIESLEKESA
                     FKTKAEPISSSISNMELELNIHNSKAPKKNRLRRKSSTRHIHALELVVSRNLSPPNCT
                     ELQIDSCSSSEEIKKKKYNQMPVRHSRNLQLMEGKEPATGAKKSNKPNEQTSKRHDSD
                     TFPELKLTNAPGSFTKCSNTSELKEFVNPSLPREEKEEKLETVKVSNNAEDPKDLMLS
                     GERVLQTERSVESSSISLVPGTDYGTQESISLLEVSTLGKAKTEPNKCVSQCAAFENP
                     KGLIHGCSKDNRNDTEGFKYPLGHEVNHSRETSIEMEESELDAQYLQNTFKVSKRQSF
                     APFSNPGNAEEECATFSAHSGSLKKQSPKVTFECEQKEENQGKNESNIKPVQTVNITA
                     GFPVVGQKDKPVDNAKCSIKGGSRFCLSSQFRGNETGLITPNKHGLLQNPYRIPPLFP
                     IKSFVKTKCKKNLLEENFEEHSMSPEREMGNENIPSTVSTISRNNIRENVFKEASSSN
                     INEVGSSTNEVGSSINEIGSSDENIQAELGRNRGPKLNAMLRLGVLQPEVYKQSLPGS
                     NCKHPEIKKQEYEEVVQTVNTDFSPYLISDNLEQPMGSSHASQVCSETPDDLLDDGEI
                     KEDTSFAENDIKESSAVFSKSVQKGELSRSPSPFTHTHLAQGYRRGAKKLESSEENLS
                     SEDEELPCFQHLLFGKVNNIPSQSTRHSTVATECLSKNTEENLLSLKNSLNDCSNQVI
                     LAKASQEHHLSEETKCSASLFSSQCSELEDLTANTNTQDPFLIGSSKQMRHQSESQGV
                     GLSDKELVSDDEERGTGLEENNQEEQSMDSNLGEAASGCESETSVSEDCSGLSSQSDI
                     LTTQQRDTMQHNLIKLQQEMAELEAVLEQHGSQPSNSYPSIISDSSALEDLRNPEQST
                     SEKAVLTSQKSSEYPISQNPEGLSADKFEVSADSSTSKNKEPGVERSSPSKCPSLDDR
                     WYMHSCSGSLQNRNYPSQEELIKVVDVEEQQLEESGPHDLTETSYLPRQDLEGTPYLE
                     SGISLFSDDPESDPSEDRAPESARVGNIPSSTSALKVPQLKVAESAQSPAAAHTTDTA
                     GYNAMEESVSREKPELTASTERVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLIT
                     EETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKMLNEHDFEVRGD
                     VVNGRNHQGPKRARESQDRKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSS
                     FTLGTGVHPIVVVQPDAWTEDNGFHAIGQMCEAPVVTREWVLDSVALYQCQELDTYLI
                     PQIPHSHY"
     exon            298..386
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            387..526
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            527..629
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            630..675
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            676..752
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            753..4178
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            4179..4267
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            4268..4439
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            4440..4566
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            4567..4757
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            4758..5068
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            5069..5156
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            5157..5234
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            5235..5275
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            5276..5359
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            5360..5414
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            5415..5488
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            5489..5549
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     exon            5550..7057
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /inference="alignment:Splign:2.1.0"
     regulatory      7032..7037
                     /regulatory_class="polyA_signal_sequence"
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /note="hexamer: AATAAA"
     polyA_site      7057
                     /gene="BRCA1"
                     /gene_synonym="BRCAI; BRCC1; BROVCA1; FANCS; IRIS; PNCA4;
                     PPP1R53; PSCP; RNF53"
                     /note="major polyA site"
ORIGIN      
        1 gctgagactt cctggacggg ggacaggctg tggggtttct cagataactg ggcccctgcg
       61 ctcaggaggc cttcaccctc tgctctggtt cattggaaca gaaagaaatg gatttatctg
      121 ctcttcgcgt tgaagaagta caaaatgtca ttaatgctat gcagaaaatc ttagagtgtc
      181 ccatctgtct ggagttgatc aaggaacctg tctccacaaa gtgtgaccac atattttgca
      241 aattttgcat gctgaaactt ctcaaccaga agaaagggcc ttcacagtgt cctttatgag
      301 cctacaagaa agtacgagat ttagtcaact tgttgaagag ctattgaaaa tcatttgtgc
      361 ttttcagctt gacacaggtt tggagtatgc aaacagctat aattttgcaa aaaaggaaaa
      421 taactctcct gaacatctaa aagatgaagt ttctatcatc caaagtatgg gctacagaaa
      481 ccgtgccaaa agacttctac agagtgaacc cgaaaatcct tccttggaaa ccagtctcag
      541 tgtccaactc tctaaccttg gaactgtgag aactctgagg acaaagcagc ggatacaacc
      601 tcaaaagacg tctgtctaca ttgaattggg atctgattct tctgaagata ccgttaataa
      661 ggcaacttat tgcagtgtgg gagatcaaga attgttacaa atcacccctc aaggaaccag
      721 ggatgaaatc agtttggatt ctgcaaaaaa ggctgcttgt gaattttctg agacggatgt
      781 aacaaatact gaacatcatc aacccagtaa taatgatttg aacaccactg agaagcgtgc
      841 agctgagagg catccagaaa agtatcaggg tagttctgtt tcaaacttgc atgtggagcc
      901 atgtggcaca aatactcatg ccagctcatt acagcatgag aacagcagtt tattactcac
      961 taaagacaga atgaatgtag aaaaggctga attctgtaat aaaagcaaac agcctggctt
     1021 agcaaggagc caacataaca gatgggctgg aagtaaggaa acatgtaatg ataggcggac
     1081 tcccagcaca gaaaaaaagg tagatctgaa tgctgatccc ctgtgtgaga gaaaagaatg
     1141 gaataagcag aaactgccat gctcagagaa tcctagagat actgaagatg ttccttggat
     1201 aacactaaat agcagcattc agaaagttaa tgagtggttt tccagaagtg atgaactgtt
     1261 aggttctgat gactcacatg atggggagtc tgaatcaaat gccaaagtag ctgatgtatt
     1321 ggacgttcta aatgaggtag atgaatattc tggttcttca gagaaaatag acttactggc
     1381 cagtgatcct catgaggctt taatatgtaa aagtgaaaga gttcactcca aatcagtaga
     1441 gagtaatatt gaagacaaaa tatttgggaa aacctatcgg aagaaggcaa gcctccccaa
     1501 cttaagccat gtaactgaaa atctaattat aggagcattt gttactgagc cacagataat
     1561 acaagagcgt cccctcacaa ataaattaaa gcgtaaaagg agacctacat caggccttca
     1621 tcctgaggat tttatcaaga aagcagattt ggcagttcaa aagactcctg aaatgataaa
     1681 tcagggaact aaccaaacgg agcagaatgg tcaagtgatg aatattacta atagtggtca
     1741 tgagaataaa acaaaaggtg attctattca gaatgagaaa aatcctaacc caatagaatc
     1801 actcgaaaaa gaatctgctt tcaaaacgaa agctgaacct ataagcagca gtataagcaa
     1861 tatggaactc gaattaaata tccacaattc aaaagcacct aaaaagaata ggctgaggag
     1921 gaagtcttct accaggcata ttcatgcgct tgaactagta gtcagtagaa atctaagccc
     1981 acctaattgt actgaattgc aaattgatag ttgttctagc agtgaagaga taaagaaaaa
     2041 aaagtacaac caaatgccag tcaggcacag cagaaaccta caactcatgg aaggtaaaga
     2101 acctgcaact ggagccaaga agagtaacaa gccaaatgaa cagacaagta aaagacatga
     2161 cagcgatact ttcccagagc tgaagttaac aaatgcacct ggttctttta ctaagtgttc
     2221 aaataccagt gaacttaaag aatttgtcaa tcctagcctt ccaagagaag aaaaagaaga
     2281 gaaactagaa acagttaaag tgtctaataa tgctgaagac cccaaagatc tcatgttaag
     2341 tggagaaagg gttttgcaaa ctgaaagatc tgtagagagt agcagtattt cattggtacc
     2401 tggtactgat tatggcactc aggaaagtat ctcgttactg gaagttagca ctctagggaa
     2461 ggcaaaaaca gaaccaaata aatgtgtgag tcagtgtgca gcatttgaaa accccaaggg
     2521 actaattcat ggttgttcca aagataatag aaatgacaca gaaggcttta agtatccatt
     2581 gggacatgaa gttaaccaca gtcgggaaac aagcatagaa atggaagaaa gtgaacttga
     2641 tgctcagtat ttgcagaata cattcaaggt ttcaaagcgc cagtcatttg ctccgttttc
     2701 aaatccagga aatgcagaag aggaatgtgc aacattctct gcccactctg ggtccttaaa
     2761 gaaacaaagt ccaaaagtca cttttgaatg tgaacaaaag gaagaaaatc aaggaaagaa
     2821 tgagtctaat atcaagcctg tacagacagt taatatcact gcaggctttc ctgtggttgg
     2881 tcagaaagat aagccagttg ataatgccaa atgtagtatc aaaggaggct ctaggttttg
     2941 tctatcatct cagttcagag gcaacgaaac tggactcatt actccaaata aacatggact
     3001 tttacaaaac ccatatcgta taccaccact ttttcccatc aagtcatttg ttaaaactaa
     3061 atgtaagaaa aatctgctag aggaaaactt tgaggaacat tcaatgtcac ctgaaagaga
     3121 aatgggaaat gagaacattc caagtacagt gagcacaatt agccgtaata acattagaga
     3181 aaatgttttt aaagaagcca gctcaagcaa tattaatgaa gtaggttcca gtactaatga
     3241 agtgggctcc agtattaatg aaataggttc cagtgatgaa aacattcaag cagaactagg
     3301 tagaaacaga gggccaaaat tgaatgctat gcttagatta ggggttttgc aacctgaggt
     3361 ctataaacaa agtcttcctg gaagtaattg taagcatcct gaaataaaaa agcaagaata
     3421 tgaagaagta gttcagactg ttaatacaga tttctctcca tatctgattt cagataactt
     3481 agaacagcct atgggaagta gtcatgcatc tcaggtttgt tctgagacac ctgatgacct
     3541 gttagatgat ggtgaaataa aggaagatac tagttttgct gaaaatgaca ttaaggaaag
     3601 ttctgctgtt tttagcaaaa gcgtccagaa aggagagctt agcaggagtc ctagcccttt
     3661 cacccataca catttggctc agggttaccg aagaggggcc aagaaattag agtcctcaga
     3721 agagaactta tctagtgagg atgaagagct tccctgcttc caacacttgt tatttggtaa
     3781 agtaaacaat ataccttctc agtctactag gcatagcacc gttgctaccg agtgtctgtc
     3841 taagaacaca gaggagaatt tattatcatt gaagaatagc ttaaatgact gcagtaacca
     3901 ggtaatattg gcaaaggcat ctcaggaaca tcaccttagt gaggaaacaa aatgttctgc
     3961 tagcttgttt tcttcacagt gcagtgaatt ggaagacttg actgcaaata caaacaccca
     4021 ggatcctttc ttgattggtt cttccaaaca aatgaggcat cagtctgaaa gccagggagt
     4081 tggtctgagt gacaaggaat tggtttcaga tgatgaagaa agaggaacgg gcttggaaga
     4141 aaataatcaa gaagagcaaa gcatggattc aaacttaggt gaagcagcat ctgggtgtga
     4201 gagtgaaaca agcgtctctg aagactgctc agggctatcc tctcagagtg acattttaac
     4261 cactcagcag agggatacca tgcaacataa cctgataaag ctccagcagg aaatggctga
     4321 actagaagct gtgttagaac agcatgggag ccagccttct aacagctacc cttccatcat
     4381 aagtgactct tctgcccttg aggacctgcg aaatccagaa caaagcacat cagaaaaagc
     4441 agtattaact tcacagaaaa gtagtgaata ccctataagc cagaatccag aaggcctttc
     4501 tgctgacaag tttgaggtgt ctgcagatag ttctaccagt aaaaataaag aaccaggagt
     4561 ggaaaggtca tccccttcta aatgcccatc attagatgat aggtggtaca tgcacagttg
     4621 ctctgggagt cttcagaata gaaactaccc atctcaagag gagctcatta aggttgttga
     4681 tgtggaggag caacagctgg aagagtctgg gccacacgat ttgacggaaa catcttactt
     4741 gccaaggcaa gatctagagg gaacccctta cctggaatct ggaatcagcc tcttctctga
     4801 tgaccctgaa tctgatcctt ctgaagacag agccccagag tcagctcgtg ttggcaacat
     4861 accatcttca acctctgcat tgaaagttcc ccaattgaaa gttgcagaat ctgcccagag
     4921 tccagctgct gctcatacta ctgatactgc tgggtataat gcaatggaag aaagtgtgag
     4981 cagggagaag ccagaattga cagcttcaac agaaagggtc aacaaaagaa tgtccatggt
     5041 ggtgtctggc ctgaccccag aagaatttat gctcgtgtac aagtttgcca gaaaacacca
     5101 catcacttta actaatctaa ttactgaaga gactactcat gttgttatga aaacagatgc
     5161 tgagtttgtg tgtgaacgga cactgaaata ttttctagga attgcgggag gaaaatgggt
     5221 agttagctat ttctgggtga cccagtctat taaagaaaga aaaatgctga atgagcatga
     5281 ttttgaagtc agaggagatg tggtcaatgg aagaaaccac caaggtccaa agcgagcaag
     5341 agaatcccag gacagaaaga tcttcagggg gctagaaatc tgttgctatg ggcccttcac
     5401 caacatgccc acagatcaac tggaatggat ggtacagctg tgtggtgctt ctgtggtgaa
     5461 ggagctttca tcattcaccc ttggcacagg tgtccaccca attgtggttg tgcagccaga
     5521 tgcctggaca gaggacaatg gcttccatgc aattgggcag atgtgtgagg cacctgtggt
     5581 gacccgagag tgggtgttgg acagtgtagc actctaccag tgccaggagc tggacaccta
     5641 cctgataccc cagatccccc acagccacta ctgactgcag ccagccacag gtacagagcc
     5701 acaggacccc aagaatgagc ttacaaagtg gcctttccag gccctgggag ctcctctcac
     5761 tcttcagtcc ttctactgtc ctggctacta aatattttat gtacatcagc ctgaaaagga
     5821 cttctggcta tgcaagggtc ccttaaagat tttctgcttg aagtctccct tggaaatctg
     5881 ccatgagcac aaaattatgg taatttttca cctgagaaga ttttaaaacc atttaaacgc
     5941 caccaattga gcaagatgct gattcattat ttatcagccc tattctttct attcaggctg
     6001 ttgttggctt agggctggaa gcacagagtg gcttggcctc aagagaatag ctggtttccc
     6061 taagtttact tctctaaaac cctgtgttca caaaggcaga gagtcagacc cttcaatgga
     6121 aggagagtgc ttgggatcga ttatgtgact taaagtcaga atagtccttg ggcagttctc
     6181 aaatgttgga gtggaacatt ggggaggaaa ttctgaggca ggtattagaa atgaaaagga
     6241 aacttgaaac ctgggcatgg tggctcacgc ctgtaatccc agcactttgg gaggccaagg
     6301 tgggcagatc actggaggtc aggagttcga aaccagcctg gccaacatgg tgaaacccca
     6361 tctctactaa aaatacagaa attagccggt catggtggtg gacacctgta atcccagcta
     6421 ctcaggtggc taaggcagga gaatcacttc agcccgggag gtggaggttg cagtgagcca
     6481 agatcatacc acggcactcc agcctgggtg acagtgagac tgtggctcaa aaaaaaaaaa
     6541 aaaaaaagga aaatgaaact agaagagatt tctaaaagtc tgagatatat ttgctagatt
     6601 tctaaagaat gtgttctaaa acagcagaag attttcaaga accggtttcc aaagacagtc
     6661 ttctaattcc tcattagtaa taagtaaaat gtttattgtt gtagctctgg tatataatcc
     6721 attcctctta aaatataaga cctctggcat gaatatttca tatctataaa atgacagatc
     6781 ccaccaggaa ggaagctgtt gctttctttg aggtgatttt tttcctttgc tccctgttgc
     6841 tgaaaccata cagcttcata aataattttg cttgctgaag gaagaaaaag tgtttttcat
     6901 aaacccatta tccaggactg tttatagctg ttggaaggac taggtcttcc ctagcccccc
     6961 cagtgtgcaa gggcagtgaa gacttgattg tacaaaatac gttttgtaaa tgttgtgctg
     7021 ttaacactgc aaataaactt ggtagcaaac acttcca
//
