LOCUS       NM_001017975            4899 bp    mRNA    linear   PRI 01-JUN-2024
DEFINITION  Homo sapiens helicase for meiosis 1 (HFM1), transcript variant 1,
            mRNA.
ACCESSION   NM_001017975 XM_371267
VERSION     NM_001017975.6
KEYWORDS    RefSeq; MANE Select.
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 4899)
  AUTHORS   Yu,L., Li,M., Zhang,H., He,Q., Wan,F., Zhang,C. and Wang,F.
  TITLE     Novel pathogenic splicing variants in helicase for meiosis 1 (HFM1)
            are associated with diminished ovarian reserve and poor pregnancy
            outcomes
  JOURNAL   J Assist Reprod Genet 39 (9), 2135-2141 (2022)
   PUBMED   35881270
  REMARK    GeneRIF: Novel pathogenic splicing variants in helicase for meiosis
            1 (HFM1) are associated with diminished ovarian reserve and poor
            pregnancy outcomes.
REFERENCE   2  (bases 1 to 4899)
  AUTHORS   Xie,X., Murtaza,G., Li,Y., Zhou,J., Ye,J., Khan,R., Jiang,L.,
            Khan,I., Zubair,M., Yin,H., Jiang,H., Liu,W., Shi,B., Hou,X.,
            Gong,C., Fan,S., Wang,Y., Jiang,X., Zhang,Y., Zhang,H., Ma,H. and
            Shi,Q.
  TITLE     Biallelic HFM1 variants cause non-obstructive azoospermia with
            meiotic arrest in humans by impairing crossover formation to
            varying degrees
  JOURNAL   Hum Reprod 37 (7), 1664-1677 (2022)
   PUBMED   35526155
  REMARK    GeneRIF: Biallelic HFM1 variants cause non-obstructive azoospermia
            with meiotic arrest in humans by impairing crossover formation to
            varying degrees.
REFERENCE   3  (bases 1 to 4899)
  AUTHORS   Saebnia,N., Ebrahimzadeh-Vesal,R., Haddad-Mashhadrizeh,A.,
            Gholampour-Faroji,N., Schinzel,A., Neshati,Z. and Azimi-Nezhad,M.
  TITLE     Identification of a new splice-acceptor mutation in HFM1 and
            functional analysis through molecular docking in nonobstructive
            azoospermia
  JOURNAL   J Assist Reprod Genet 39 (5), 1195-1203 (2022)
   PUBMED   35486194
  REMARK    GeneRIF: Identification of a new splice-acceptor mutation in HFM1
            and functional analysis through molecular docking in nonobstructive
            azoospermia.
REFERENCE   4  (bases 1 to 4899)
  AUTHORS   Tang,D., Lv,M., Gao,Y., Cheng,H., Li,K., Xu,C., Geng,H., Li,G.,
            Shen,Q., Wang,C., He,X. and Cao,Y.
  TITLE     Novel variants in helicase for meiosis 1 lead to male infertility
            due to non-obstructive azoospermia
  JOURNAL   Reprod Biol Endocrinol 19 (1), 129 (2021)
   PUBMED   34429122
  REMARK    GeneRIF: Novel variants in helicase for meiosis 1 lead to male
            infertility due to non-obstructive azoospermia.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 4899)
  AUTHORS   Zhe,J., Chen,S., Chen,X., Liu,Y., Li,Y., Zhou,X. and Zhang,J.
  TITLE     A novel heterozygous splice-altering mutation in HFM1 may be a
            cause of premature ovarian insufficiency
  JOURNAL   J Ovarian Res 12 (1), 61 (2019)
   PUBMED   31279343
  REMARK    GeneRIF: A novel heterozygous missense mutation in HFM1 (c.3470G >
            A) associated with premature ovarian insufficiency (POI) is in the
            affected family members and absent in the unaffected family members
            in China. Results of the minigene assay reveals that the mutation
            changes the mRNA splicing repertory.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 4899)
  AUTHORS   Pu,D., Wang,C., Cao,J., Shen,Y., Jiang,H., Liu,J., Wu,B.L.,
            Zhang,W. and Wu,J.
  TITLE     Association analysis between HFM1 variation and primary ovarian
            insufficiency in Chinese women
  JOURNAL   Clin Genet 89 (5), 597-602 (2016)
   PUBMED   26679638
  REMARK    GeneRIF: Data suggest that HFM1 gene might be associated with
            primary ovarian insufficiency in Chinese population.
REFERENCE   7  (bases 1 to 4899)
  AUTHORS   Wang,J., Zhang,W., Jiang,H. and Wu,B.L.
  CONSRTM   Primary Ovarian Insufficiency Collaboration
  TITLE     Mutations in HFM1 in recessive primary ovarian insufficiency
  JOURNAL   N Engl J Med 370 (10), 972-974 (2014)
   PUBMED   24597873
  REMARK    GeneRIF: Exome sequencing of two Chinese sisters with primary
            ovarian insufficiency and their parents identified a shared
            compound heterozygous mutation in a meiotic gene, HFM1, which
            encodes a protein necessary for homologous recombination of
            chromosomes.
REFERENCE   8  (bases 1 to 4899)
  AUTHORS   Guiraldelli,M.F., Eyster,C., Wilkerson,J.L., Dresser,M.E. and
            Pezza,R.J.
  TITLE     Mouse HFM1/Mer3 is required for crossover formation and complete
            synapsis of homologous chromosomes during meiosis
  JOURNAL   PLoS Genet 9 (3), e1003383 (2013)
   PUBMED   23555294
REFERENCE   9  (bases 1 to 4899)
  AUTHORS   Flachsbart,F., Franke,A., Kleindorp,R., Caliebe,A., Blanche,H.,
            Schreiber,S. and Nebel,A.
  TITLE     Investigation of genetic susceptibility factors for human longevity
            - a targeted nonsynonymous SNP study
  JOURNAL   Mutat Res 694 (1-2), 13-19 (2010)
   PUBMED   20800603
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   10 (bases 1 to 4899)
  AUTHORS   Tanaka,K., Miyamoto,N., Shouguchi-Miyata,J. and Ikeda,J.E.
  TITLE     HFM1, the human homologue of yeast Mer3, encodes a putative DNA
            helicase expressed specifically in germ-line cells
  JOURNAL   DNA Seq 17 (3), 242-246 (2006)
   PUBMED   17286053
  REMARK    GeneRIF: hHFM1 is the evolutionally conserved putative human DNA
            helicase, which may function as a modulator for genome integrity in
            germ-line tissues.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC098691.2 and BX323048.4.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Feb 3, 2020 this sequence version replaced NM_001017975.5.
            
            Summary: The protein encoded by this gene is thought to be an
            ATP-dependent DNA helicase and is expressed mainly in germ-line
            cells. Defects in this gene are a cause of premature ovarian
            failure 9 (POF9). [provided by RefSeq, Apr 2014].
            
            ##Evidence-Data-START##
            Transcript exon combination :: AB204867.1, SRR18074967.2873938.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000370425.8/ ENSP00000359454.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-40                AC098691.2         70177-70216         c
            41-138              AC098691.2         66391-66488         c
            139-251             AC098691.2         61672-61784         c
            252-561             AC098691.2         59472-59781         c
            562-821             AC098691.2         50954-51213         c
            822-869             AC098691.2         50566-50613         c
            870-940             AC098691.2         46291-46361         c
            941-1073            AC098691.2         45483-45615         c
            1074-1225           AC098691.2         44442-44593         c
            1226-1303           AC098691.2         43782-43859         c
            1304-1462           AC098691.2         43404-43562         c
            1463-1663           AC098691.2         40906-41106         c
            1664-1752           AC098691.2         40737-40825         c
            1753-1796           AC098691.2         18635-18678         c
            1797-1898           AC098691.2         18430-18531         c
            1899-2044           AC098691.2         17885-18030         c
            2045-2139           AC098691.2         16928-17022         c
            2140-2273           AC098691.2         16117-16250         c
            2274-2321           AC098691.2         12808-12855         c
            2322-2402           AC098691.2         8809-8889           c
            2403-2494           BX323048.4         102730-102821       c
            2495-2601           BX323048.4         101148-101254       c
            2602-2649           BX323048.4         101005-101052       c
            2650-2747           BX323048.4         97348-97445         c
            2748-2879           BX323048.4         97133-97264         c
            2880-2965           BX323048.4         94446-94531         c
            2966-3049           BX323048.4         94156-94239         c
            3050-3207           BX323048.4         93870-94027         c
            3208-3311           BX323048.4         92012-92115         c
            3312-3458           BX323048.4         91404-91550         c
            3459-3539           BX323048.4         55037-55117         c
            3540-3655           BX323048.4         54683-54798         c
            3656-3735           BX323048.4         52785-52864         c
            3736-3839           BX323048.4         51767-51870         c
            3840-3950           BX323048.4         45800-45910         c
            3951-4041           BX323048.4         44072-44162         c
            4042-4153           BX323048.4         40536-40647         c
            4154-4305           BX323048.4         40296-40447         c
            4306-4899           BX323048.4         38821-39414         c
FEATURES             Location/Qualifiers
     source          1..4899
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p22.2"
     gene            1..4899
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /note="helicase for meiosis 1"
                     /db_xref="GeneID:164045"
                     /db_xref="HGNC:HGNC:20193"
                     /db_xref="MIM:615684"
     exon            1..40
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            41..138
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     CDS             68..4375
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /EC_number="3.6.4.12"
                     /note="helicase-like protein HFM1; SEC63 domain-containing
                     protein 1; HFM1, ATP dependent DNA helicase homolog"
                     /codon_start=1
                     /product="probable ATP-dependent DNA helicase HFM1"
                     /protein_id="NP_001017975.5"
                     /db_xref="CCDS:CCDS30769.2"
                     /db_xref="GeneID:164045"
                     /db_xref="HGNC:HGNC:20193"
                     /db_xref="MIM:615684"
                     /translation="MLKSNDCLFSLENLFFEKPDEVENHPDNEKSLDWFLPPAPLISE
                     IPDTQELEEELESHKLLGQEKRPKMLTSNLKITNEDTNYISLTQKFQFAFPSDKYEQD
                     DLNLEGVGNNDLSHIAGKLTYASQKYKNHIGTEIAPEKSVPDDTKLVNFAEDKGESTS
                     VFRKRLFKISDNIHGSAYSNDNELDSHIGSVKIVQTEMNKGKSRNYSNSKQKFQYSAN
                     VFTANNAFSASEIGEGMFKAPSFSVAFQPHDIQEVTENGLGSLKAVTEIPAKFRSIFK
                     EFPYFNYIQSKAFDDLLYTDRNFVICAPTGSGKTVVFELAITRLLMEVPLPWLNIKIV
                     YMAPIKALCSQRFDDWKEKFGPIGLNCKELTGDTVMDDLFEIQHAHIIMTTPEKWDSM
                     TRKWRDNSLVQLVRLFLIDEVHIVKDENRGPTLEVVVSRMKTVQSVSQTLKNTSTAIP
                     MRFVAVSATIPNAEDIAEWLSDGERPAVCLKMDESHRPVKLQKVVLGFPCSSNQTEFK
                     FDLTLNYKIASVIQMYSDQKPTLVFCATRKGVQQAASVLVKDAKFIMTVEQKQRLQKY
                     AYSVRDSKLRDILKDGAAYHHAGMELSDRKVVEGAFTVGDLPVLFTTSTLAMGVNLPA
                     HLVVIKSTMHYAGGLFEEYSETDILQMIGRAGRPQFDTTATAVIMTRLSTRDKYIQML
                     ACRDTVESSLHRHLIEHLNAEIVLHTITDVNIAVEWIRSTLLYIRALKNPSHYGFASG
                     LNKDGIEAKLQELCLKNLNDLSSLDLIKMDEGVNFKPTEAGRLMAWYYITFETVKKFY
                     TISGKETLSDLVTLIAGCKEFLDIQLRINEKKTLNTLNKDPNRITIRFPMEGRIKTRE
                     MKVNCLIQAQLGCIPIQDFALTQDTAKIFRHGSRITRWLSDFVAAQEKKFAVLLNSLI
                     LAKCFRCKLWENSLHVSKQLEKIGITLSNAIVNAGLTSFKKIEETDARELELILNRHP
                     PFGTQIKETVMYLPKYELKVEQITRYSDTTAEILVTVILRNFEQLQTKRTASDSHYVT
                     LIIGDADNQVVYLHKITDSVLLKAGSWAKKIAVKRALKSEDLSINLISSEFVGLDIQQ
                     KLTVFYLEPKRFGNQITMQRKSETQISHSKHSDISTIAGPNKGTTASKKPGNRECNHL
                     CKSKHTCGHDCCKIGVAQKSEIKESTISSYLSDLRNRNAVSSVPPVKRLKIQMNKSQS
                     VDLKEFGFTPKPSLPSISRSEYLNISELPIMEQWDQPEIYGKVRQEPSEYQDKEVLNV
                     NFELGNEVWDDFDDENLEVTSFSTDTEKTKISGFGNTLSSSTRGSKLPLQESKSKFQR
                     EMSNSFVSSHEMSDISLSNSAMPKFSASSMTKLPQQAGNAVIVHFQERKPQNLSPEIE
                     KQCFTFSEKNPNSSNYKKVDFFIRNSECKKEVDFSMYHPDDEADEMKSLLGIFDGIF"
     exon            139..251
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            252..561
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            562..821
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            822..869
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            870..940
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            941..1073
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            1074..1225
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            1226..1303
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            1304..1462
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            1463..1663
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            1664..1752
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            1753..1796
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            1797..1898
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            1899..2044
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2045..2139
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2140..2273
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2274..2321
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2322..2402
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2403..2494
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2495..2601
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2602..2649
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2650..2747
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2748..2879
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2880..2965
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            2966..3049
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            3050..3207
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            3208..3311
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            3312..3458
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            3459..3539
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            3540..3655
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            3656..3735
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            3736..3839
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            3840..3950
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            3951..4041
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            4042..4153
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            4154..4305
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     exon            4306..4899
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4877..4882
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /note="hexamer: AATAAA"
     polyA_site      4899
                     /gene="HFM1"
                     /gene_synonym="helicase; MER3; POF9; SEC63D1; Si-11;
                     Si-11-6"
                     /note="major polyA site"
ORIGIN      
        1 aaatcggcgc tcgactggcc taggagctgt ccgcagggag atttatgaca aagtccagtt
       61 ttcaacaatg ctgaaatcaa atgattgcct gttttctttg gaaaatttgt tttttgaaaa
      121 accagatgaa gttgaaaacc atccagacaa tgaaaagtca ttggattggt ttctccctcc
      181 tgctccattg atttcagaaa ttccagatac tcaggagtta gaggaagaat tagaaagtca
      241 taaactgtta ggtcaggaaa agaggccaaa aatgttaaca tcaaatttaa agataactaa
      301 tgaagataca aattatattt cactaacaca aaaattccag tttgcctttc cttctgataa
      361 atatgaacag gatgatctaa atttagaagg ggtaggtaat aatgacttat cacatattgc
      421 tggcaagctg acatatgctt ctcagaaata taaaaatcac attggcactg agatagcacc
      481 tgagaagagt gttcctgatg atacaaaatt agttaatttt gcagaagata aaggagagag
      541 cacatcagta ttccggaaaa gattatttaa aatatctgac aatatacatg ggagtgctta
      601 ttctaatgac aatgaattgg actctcacat tggctcagtg aaaattgtac aaacagaaat
      661 gaacaaaggg aaatcaagga actatagcaa tagtaagcaa aaatttcagt attctgcaaa
      721 tgtgtttaca gcaaataatg ctttttctgc ttctgaaatc ggagaaggca tgttcaaagc
      781 accatctttt tcagttgctt tccaacctca tgatattcaa gaggtaacag aaaatggttt
      841 aggttccttg aaggctgtca cagaaattcc ggcaaaattt agaagtattt tcaaagaatt
      901 tccatatttc aactatatac agtccaaggc ctttgatgat cttctttaca cagataggaa
      961 ttttgtgatt tgtgctccaa ctggttctgg aaaaactgta gtgtttgaac tagctataac
     1021 aagattgtta atggaagtac cattgccatg gttgaatatt aaaattgttt acatggcacc
     1081 aataaaagcc ttgtgcagtc agcgttttga tgactggaaa gaaaaatttg gaccaatagg
     1141 attgaattgt aaagaactta ctggagatac agtaatggat gatctatttg agattcagca
     1201 tgcccatatt attatgacaa ctccagaaaa atgggatagc atgactagga aatggagaga
     1261 caactctttg gttcagctgg ttcgactgtt tctcattgat gaggtacata ttgtaaaaga
     1321 tgaaaatcgt ggtccaactc ttgaagttgt agttagcaga atgaaaactg tacagtctgt
     1381 ttctcagact ttaaaaaata ccagcactgc tattccaatg cgatttgtag ctgtatctgc
     1441 aacaattcca aatgctgagg atattgcaga atggctttca gatggtgaaa gaccagctgt
     1501 gtgtctgaaa atggatgaga gccatagacc agtgaaactt cagaaagtgg tccttggatt
     1561 tccctgcagt agtaaccaaa ctgagtttaa gtttgattta accctcaact acaaaattgc
     1621 cagtgttata caaatgtact ctgatcagaa acccacactt gtgttttgtg caacaaggaa
     1681 gggtgtgcaa caggctgctt ctgttcttgt gaaagatgct aaatttatta tgactgtgga
     1741 acagaaacag aggttacaga agtatgcata ttccgtaaga gattcaaaac tgagagatat
     1801 cttaaaagat ggtgctgctt atcatcatgc tggtatggag ctgtcagata gaaaagtagt
     1861 tgagggagct tttactgttg gagatttacc agttcttttt actaccagta ctttagctat
     1921 gggagtaaat ttgcctgctc acctagtagt tataaaatct acaatgcatt atgctggagg
     1981 actgtttgaa gagtacagtg aaacagatat tctacagatg attggtagag ctggtcgacc
     2041 tcaatttgac actacagcta ctgcagttat catgactcga ttaagcacaa gggacaagta
     2101 cattcagatg ttagcttgta gagacactgt agaaagcagt ttgcacagac atcttattga
     2161 acatttaaat gcagagatag tactgcatac catcacggat gtgaatattg ctgtggaatg
     2221 gatacgatca actctgcttt atatcagagc cttgaaaaat ccatctcatt atggttttgc
     2281 atctggattg aacaaagatg gaattgaagc aaaattacaa gaattatgtt tgaagaatct
     2341 gaatgattta tcatccctgg acttaataaa gatggatgaa ggtgttaatt tcaaaccaac
     2401 tgaagcagga agattgatgg cttggtatta tattacattt gagacagtga agaaatttta
     2461 tacaatcagt ggaaaagaaa ccttatcaga tctggttaca ttgatagctg gctgcaagga
     2521 atttctagat atacagttaa ggataaatga aaagaaaaca ctgaatactt tgaacaaaga
     2581 tccaaatcgg ataactatca gatttccaat ggaaggaaga attaaaacaa gagaaatgaa
     2641 agtaaattgt cttattcagg ctcaactagg atgcattccc atacaagatt ttgctttgac
     2701 acaagatacc gcaaagattt tcagacatgg ctcccgaatt acaagatggt tgtcagattt
     2761 tgtagctgct caagaaaaga agtttgctgt actattgaat agtttgattt tagctaaatg
     2821 ttttaggtgt aaactttggg aaaactctct gcatgtatcc aaacaactgg aaaaaattgg
     2881 tataacattg tcaaatgcaa tcgtaaatgc tggtttgact tcctttaaaa aaatagaaga
     2941 gacagatgca agggaacttg aattgatttt aaacagacat cccccctttg gaacccagat
     3001 aaaagaaact gtgatgtatc taccaaaata tgaacttaaa gtggaacaga ttacaagata
     3061 tagtgatacg acggcagaaa tattagtgac tgttatatta agaaattttg aacagctaca
     3121 aactaaaaga acagcatcgg attctcacta tgttacctta atcataggtg acgcagataa
     3181 tcaagtagtt tatctgcaca agattacgga ttctgttttg ctaaaagctg gaagttgggc
     3241 taaaaagatt gctgtgaaaa gagctcttaa atctgaagat cttagcataa atctaataag
     3301 ttctgaattt gttgggcttg atattcagca gaaacttaca gtcttttact tagaacccaa
     3361 gaggtttgga aatcaaatca ctatgcaaag aaaatctgaa acacagattt cccattctaa
     3421 acattcagac atatctacaa tagcaggacc taataaagga acgactgcca gcaaaaaacc
     3481 tgggaaccga gaatgcaatc atctttgtaa aagtaaacat acatgtggac atgactgctg
     3541 taaaattgga gttgcacaga agtcagaaat taaagagtca acaatttctt catatttatc
     3601 tgatttaaga aacaggaatg ctgtttcatc tgttcctcca gttaaacgtc tgaagataca
     3661 gatgaataaa tctcaaagtg tggaccttaa agagtttggt tttactccaa aaccttccct
     3721 tcctagtata tcaaggtcag aatatttaaa catatctgaa ttgcctataa tggagcagtg
     3781 ggatcagcct gaaatctatg gaaaagttag acaagaacca tctgaatatc aagacaaaga
     3841 agttttgaat gtgaactttg aattgggaaa tgaagtttgg gatgattttg atgatgaaaa
     3901 cttagaagtt actagctttt caactgatac tgagaagaca aaaatatcag gatttggaaa
     3961 cactttgagt tcaagtacca ggggaagtaa gctacccctt caagagtcaa agagcaaatt
     4021 ccaaagagaa atgtcaaaca gttttgtttc atcacatgag atgtcggata tttctttatc
     4081 aaattctgct atgcccaagt tcagtgcatc ctccatgaca aaattacctc aacaagccgg
     4141 aaatgcagtt attgtccatt ttcaagaaag aaaaccacaa aatctgtcac cagagattga
     4201 gaagcaatgc tttactttct ctgaaaaaaa cccaaattct tcaaattata aaaaagtgga
     4261 tttttttatt agaaacagtg aatgtaaaaa ggaagttgat ttcagtatgt atcatcctga
     4321 tgatgaagct gatgaaatga agtctttatt gggaatattt gatggtattt tctaaaacaa
     4381 acaaatactt tttatattga taagagaaag aataaagaca cctaatcaca aagcatgctt
     4441 tttattttta aaaagtagtt cataattgtt cggatttttt tctcctgtat ttgattagct
     4501 ttgttcactt tttgcaacaa aatgtatggg ccgatttatt ttcccattat attgtaactt
     4561 cttgaaaagc tcttttacag tggctttgtt tcaataagcc cttaagttaa gggctgattg
     4621 cacttagaaa taagttgcac ttagaaataa ttatttggct attaattgga ttttgacaag
     4681 aaccaatgta aaatttcatt tttatatttt cttaacaaga agaaaaatat tctatgaaag
     4741 caaagtaatg ctaacttaat gaatctgctt attgtatgga ttaatcacta atattattcc
     4801 catgtatttt gttttactaa agatttttaa gaatccagtg gctatttgaa cctactgtta
     4861 tctaactttg agcaacaata aatgaaacat taatcagta
//
