LOCUS       NM_018136              10863 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens assembly factor for spindle microtubules (ASPM),
            transcript variant 1, mRNA.
ACCESSION   NM_018136 NM_018123
VERSION     NM_018136.5
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 10863)
  AUTHORS   Zhang,Y., Che,N., Wang,S., Meng,J., Zhao,N., Han,J., Dong,X.,
            Li,Y., Mo,J., Zhao,X. and Liu,T.
  TITLE     Nrf2/ASPM axis regulated vasculogenic mimicry formation in
            hepatocellular carcinoma under hypoxia
  JOURNAL   J Gastroenterol 59 (10), 941-957 (2024)
   PUBMED   39097533
  REMARK    GeneRIF: Nrf2/ASPM axis regulated vasculogenic mimicry formation in
            hepatocellular carcinoma under hypoxia.
REFERENCE   2  (bases 1 to 10863)
  AUTHORS   Chang,J., Zhang,Y., Zhou,T., Qiao,Q., Shan,J., Chen,Y., Jiang,W.,
            Wang,Y., Liu,S., Wang,Y., Yu,Y., Li,C. and Li,X.
  TITLE     RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated
            beta-catenin signaling in cholangiocarcinoma
  JOURNAL   J Exp Clin Cancer Res 43 (1), 104 (2024)
   PUBMED   38576051
  REMARK    GeneRIF: RBM10 C761Y mutation induced oncogenic ASPM isoforms and
            regulated beta-catenin signaling in cholangiocarcinoma.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 10863)
  AUTHORS   Chan,T.S., Cheng,L.H., Hsu,C.C., Yang,P.M., Liao,T.Y., Hsieh,H.Y.,
            Lin,P.C., HuangFu,W.C., Chuu,C.P. and Tsai,K.K.
  TITLE     ASPM stabilizes the NOTCH intracellular domain 1 and promotes
            oncogenesis by blocking FBXW7 binding in hepatocellular carcinoma
            cells
  JOURNAL   Mol Oncol 18 (3), 562-579 (2024)
   PUBMED   38279565
  REMARK    GeneRIF: ASPM stabilizes the NOTCH intracellular domain 1 and
            promotes oncogenesis by blocking FBXW7 binding in hepatocellular
            carcinoma cells.
REFERENCE   4  (bases 1 to 10863)
  AUTHORS   Li,N., Chu,J., Hu,K., Zhang,H., Li,N., Chu,J.F., Hu,K.Y. and
            Zhang,H.Y.
  TITLE     ASPM overexpression enhances cellular proliferation and migration
            and predicts worse prognosis for papillary renal cell carcinoma
  JOURNAL   J Biosci 48 (2023)
   PUBMED   37309171
  REMARK    GeneRIF: ASPM overexpression enhances cellular proliferation and
            migration and predicts worse prognosis for papillary renal cell
            carcinoma.
REFERENCE   5  (bases 1 to 10863)
  AUTHORS   Kumar,A., Markandaya,M. and Girimaji,S.C.
  TITLE     Primary microcephaly: microcephalin and ASPM determine the size of
            the human brain
  JOURNAL   J Biosci 27 (7), 629-632 (2002)
   PUBMED   12571366
  REMARK    GeneRIF: microcephalin and ASPM determine the size of the human
            brain
REFERENCE   6  (bases 1 to 10863)
  AUTHORS   Bond,J., Roberts,E., Mochida,G.H., Hampshire,D.J., Scott,S.,
            Askham,J.M., Springell,K., Mahadevan,M., Crow,Y.J., Markham,A.F.,
            Walsh,C.A. and Woods,C.G.
  TITLE     ASPM is a major determinant of cerebral cortical size
  JOURNAL   Nat Genet 32 (2), 316-320 (2002)
   PUBMED   12355089
  REMARK    GeneRIF: Similar to aspm of Drosophila.  Regulates brain size by
            regulating mitotic spindle activity in neuronal progenitor cells.
REFERENCE   7  (bases 1 to 10863)
  AUTHORS   do Carmo Avides,M., Tavares,A. and Glover,D.M.
  TITLE     Polo kinase and Asp are needed to promote the mitotic organizing
            activity of centrosomes
  JOURNAL   Nat Cell Biol 3 (4), 421-424 (2001)
   PUBMED   11283617
REFERENCE   8  (bases 1 to 10863)
  AUTHORS   Pattison,L., Crow,Y.J., Deeble,V.J., Jackson,A.P., Jafri,H.,
            Rashid,Y., Roberts,E. and Woods,C.G.
  TITLE     A fifth locus for primary autosomal recessive microcephaly maps to
            chromosome 1q31
  JOURNAL   Am J Hum Genet 67 (6), 1578-1580 (2000)
   PUBMED   11078481
REFERENCE   9  (bases 1 to 10863)
  AUTHORS   Verloes,A., Drunat,S. and Passemard,S.
  TITLE     ASPM Primary Microcephaly
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   32239881
REFERENCE   10 (bases 1 to 10863)
  AUTHORS   Verloes,A., Drunat,S., Gressens,P. and Passemard,S.
  TITLE     Primary Autosomal Recessive Microcephalies and Seckel Syndrome
            Spectrum Disorders - RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301772
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK125107.1, AF509326.1,
            AL353809.20, BC034607.1 and BX648804.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_018136.4.
            
            Summary: This gene is the human ortholog of the Drosophila
            melanogaster 'abnormal spindle' gene (asp), which is essential for
            normal mitotic spindle function in embryonic neuroblasts. Studies
            in mouse also suggest a role of this gene in mitotic spindle
            regulation, with a preferential role in regulating neurogenesis.
            Mutations in this gene are associated with microcephaly primary
            type 5. Multiple transcript variants encoding different isoforms
            have been found for this gene.[provided by RefSeq, May 2011].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            Sequence Note: The RefSeq transcript and protein were derived from
            transcript and genomic sequence to make the sequence consistent
            with the reference genome assembly. The genomic coordinates used
            for the transcript record were based on alignments.
            
            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 :: AY367065.1, AF509326.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000367409.9/ ENSP00000356379.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-660               AK125107.1         26-685
            661-1080            AF509326.1         429-848
            1081-2153           AL353809.20        151659-152731       c
            2154-3810           AF509326.1         1922-3578
            3811-3830           BC034607.1         1455-1474
            3831-4680           AF509326.1         3599-4448
            4681-9052           AL353809.20        109759-114130       c
            9053-10858          BC034607.1         1942-3747
            10859-10863         BX648804.1         5738-5742
FEATURES             Location/Qualifiers
     source          1..10863
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q31.3"
     gene            1..10863
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /note="assembly factor for spindle microtubules"
                     /db_xref="GeneID:259266"
                     /db_xref="HGNC:HGNC:19048"
                     /db_xref="MIM:605481"
     exon            1..529
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     CDS             233..10666
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /note="isoform 1 is encoded by transcript variant 1;
                     abnormal spindle-like microcephaly-associated protein;
                     abnormal spindle microtubule assembly; asp (abnormal
                     spindle) homolog, microcephaly associated"
                     /codon_start=1
                     /product="abnormal spindle-like microcephaly-associated
                     protein isoform 1"
                     /protein_id="NP_060606.3"
                     /db_xref="CCDS:CCDS1389.1"
                     /db_xref="GeneID:259266"
                     /db_xref="HGNC:HGNC:19048"
                     /db_xref="MIM:605481"
                     /translation="MANRRVGRGCWEVSPTERRPPAGLRGPAAEEEASSPPVLSLSHF
                     CRSPFLCFGDVLLGASRTLSLALDNPNEEVAEVKISHFPAADLGFSVSQRCFVLQPKE
                     KIVISVNWTPLKEGRVREIMTFLVNDVLKHQAILLGNAEEQKKKKRSLWDTIKKKKIS
                     ASTSHNRRVSNIQNVNKTFSVSQKVDRVRSPLQACENLAMNEGGPPTENNSLILEENK
                     IPISPISPAFNECHGATCLPLSVRRSTTYSSLHASENRELLNVHSANVSKVSFNEKAV
                     TETSFNSVNVNGQRGENSKLSLTPNCSSTLNITQSQIHFLSPDSFVNNSHGANNELEL
                     VTCLSSDMFMKDNSQPVHLESTIAHEIYQKILSPDSFIKDNYGLNQDLESESVNPILS
                     PNQFLKDNMAYMCTSQQTCKVPLSNENSQVPQSPEDWRKSEVSPRIPECQGSKSPKAI
                     FEELVEMKSNYYSFIKQNNPKFSAVQDISSHSHNKQPKRRPILSATVTKRKATCTREN
                     QTEINKPKAKRCLNSAVGEHEKVINNQKEKEDFHSYLPIIDPILSKSKSYKNEVTPSS
                     TTASVARKRKSDGSMEDANVRVAITEHTEVREIKRIHFSPSEPKTSAVKKTKNVTTPI
                     SKRISNREKLNLKKKTDLSIFRTPISKTNKRTKPIIAVAQSSLTFIKPLKTDIPRHPM
                     PFAAKNMFYDERWKEKQEQGFTWWLNFILTPDDFTVKTNISEVNAATLLLGIENQHKI
                     SVPRAPTKEEMSLRAYTARCRLNRLRRAACRLFTSEKMVKAIKKLEIEIEARRLIVRK
                     DRHLWKDVGERQKVLNWLLSYNPLWLRIGLETTYGELISLEDNSDVTGLAMFILNRLL
                     WNPDIAAEYRHPTVPHLYRDGHEEALSKFTLKKLLLLVCFLDYAKISRLIDHDPCLFC
                     KDAEFKASKEILLAFSRDFLSGEGDLSRHLGLLGLPVNHVQTPFDEFDFAVTNLAVDL
                     QCGVRLVRTMELLTQNWDLSKKLRIPAISRLQKMHNVDIVLQVLKSRGIELSDEHGNT
                     ILSKDIVDRHREKTLRLLWKIAFAFQVDISLNLDQLKEEIAFLKHTKSIKKTISLLSC
                     HSDDLINKKKGKRDSGSFEQYSENIKLLMDWVNAVCAFYNKKVENFTVSFSDGRVLCY
                     LIHHYHPCYVPFDAICQRTTQTVECTQTGSVVLNSSSESDDSSLDMSLKAFDHENTSE
                     LYKELLENEKKNFHLVRSAVRDLGGIPAMINHSDMSNTIPDEKVVITYLSFLCARLLD
                     LRKEIRAARLIQTTWRKYKLKTDLKRHQEREKAARIIQLAVINFLAKQRLRKRVNAAL
                     VIQKYWRRVLAQRKLLMLKKEKLEKVQNKAASLIQGYWRRYSTRQRFLKLKYYSIILQ
                     SRIRMIIAVTSYKRYLWATVTIQRHWRAYLRRKQDQQRYEMLKSSTLIIQSMFRKWKQ
                     RKMQSQVKATVILQRAFREWHLRKQAKEENSAIIIQSWYRMHKELRKYIYIRSCVVII
                     QKRFRCFQAQKLYKRRKESILTIQKYYKAYLKGKIERTNYLQKRAAAIQLQAAFRRLK
                     AHNLCRQIRAACVIQSYWRMRQDRVRFLNLKKTIIKFQAHVRKHQQRQKYKKMKKAAV
                     IIQTHFRAYIFAMKVLASYQKTRSAVIVLQSAYRGMQARKMYIHILTSVIKIQSYYRA
                     YVSKKEFLSLKNATIKLQSTVKMKQTRKQYLHLRAAALFIQQCYRSKKIAAQKREEYM
                     QMRESCIKLQAFVRGYLVRKQMRLQRKAVISLQSYFRMRKARQYYLKMYKAIIVIQNY
                     YHAYKAQVNQRKNFLQVKKAATCLQAAYRGYKVRQLIKQQSIAALKIQSAFRGYNKRV
                     KYQSVLQSIIKIQRWYRAYKTLHDTRTHFLKTKAAVISLQSAYRGWKVRKQIRREHQA
                     ALKIQSAFRMAKAQKQFRLFKTAALVIQQNFRAWTAGRKQCMEYIELRHAVLVLQSMW
                     KGKTLRRQLQRQHKCAIIIQSYYRMHVQQKKWKIMKKAALLIQKYYRAYSIGREQNHL
                     YLKTKAAVVTLQSAYRGMKVRKRIKDCNKAAVTIQSKYRAYKTKKKYATYRASAIIIQ
                     RWYRGIKITNHQHKEYLNLKKTAIKIQSVYRGIRVRRHIQHMHRAATFIKAMFKMHQS
                     RISYHTMRKAAIVIQVRCRAYYQGKMQREKYLTILKAVKVLQASFRGVRVRRTLRKMQ
                     TAATLIQSNYRRYRQQTYFNKLKKITKTVQQRYWAMKERNIQFQRYNKLRHSVIYIQA
                     IFRGKKARRHLKMMHIAATLIQRRFRTLMMRRRFLSLKKTAILIQRKYRAHLCTKHHL
                     QFLQVQNAVIKIQSSYRRWMIRKRMREMHRAATFIQSTFRMHRLHMRYQALKQASVVI
                     QQQYQANRAAKLQRQHYLRQRHSAVILQAAFRGMKTRRHLKSMHSSATLIQSRFRSLL
                     VRRRFISLKKATIFVQRKYRATICAKHKLYQFLHLRKAAITIQSSYRRLMVKKKLQEM
                     QRAAVLIQATFRMYRTYITFQTWKHASILIQQHYRTYRAAKLQRENYIRQWHSAVVIQ
                     AAYKGMKARQLLREKHKASIVIQSTYRMYRQYCFYQKLQWATKIIQEKYRANKKKQKV
                     FQHNELKKETCVQAGFQDMNIKKQIQEQHQAAIIIQKHCKAFKIRKHYLHLRATVVSI
                     QRRYRKLTAVRTQAVICIQSYYRGFKVRKDIQNMHRAATLIQSFYRMHRAKVDYETKK
                     TAIVVIQNYYRLYVRVKTERKNFLAVQKSVRTIQAAFRGMKVRQKLKNVSEEKMAAIV
                     NQSALCCYRSKTQYEAVQSEGVMIQEWYKASGLACSQEAEYHSQSRAAVTIQKAFCRM
                     VTRKLETQKCAALRIQFFLQMAVYRRRFVQQKRAAITLQHYFRTWQTRKQFLLYRKAA
                     VVLQNHYRAFLSAKHQRQVYLQIRSSVIIIQARSKGFIQKRKFQEIKNSTIKIQAMWR
                     RYRAKKYLCKVKAACKIQAWYRCWRAHKEYLAILKAVKIIQGCFYTKLERTRFLNVRA
                     SAIIIQRKWRAILPAKIAHEHFLMIKRHRAACLIQAHYRGYKGRQVFLRQKSAALIIQ
                     KYIRAREAGKHERIKYIEFKKSTVILQALVRGWLVRKRFLEQRAKIRLLHFTAAAYYH
                     LNAVRIQRAYKLYLAVKNANKQVNSVICIQRWFRARLQEKRFIQKYHSIKKIEHEGQE
                     CLSQRNRAASVIQKAVRHFLLRKKQEKFTSGIIKIQALWRGYSWRKKNDCTKIKAIRL
                     SLQVVNREIREENKLYKRTALALHYLLTYKHLSAILEALKHLEVVTRLSPLCCENMAQ
                     SGAISKIFVLIRSCNRSIPCMEVIRYAVQVLLNVSKYEKTTSAVYDVENCIDILLELL
                     QIYREKPGNKVADKGGSIFTKTCCLLAILLKTTNRASDVRSRSKVVDRIYSLYKLTAH
                     KHKMNTERILYKQKKNSSISIPFIPETPVRTRIVSRLKPDWVLRRDNMEEITNPLQAI
                     QMVMDTLGIPY"
     exon            530..673
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            674..2153
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            2154..2258
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            2259..2405
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            2406..2651
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            2652..2719
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            2720..2861
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            2862..2992
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            2993..3168
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            3169..3314
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            3315..3400
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            3401..3622
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            3623..3830
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            3831..3973
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            3974..4102
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            4103..4297
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            4298..9052
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            9053..9219
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            9220..9316
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            9317..9526
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            9527..9676
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            9677..9868
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            9869..10061
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            10062..10216
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            10217..10393
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            10394..10563
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     exon            10564..10863
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /inference="alignment:Splign:2.1.0"
     regulatory      10706..10711
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /note="hexamer: ATTAAA"
     polyA_site      10731
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /note="major polyA site"
     regulatory      10839..10844
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /note="hexamer: AATAAA"
     polyA_site      10863
                     /gene="ASPM"
                     /gene_synonym="ASP; Calmbp1; MCPH5"
                     /note="major polyA site"
ORIGIN      
        1 agagtcaaaa cgccatactt gtttggctcc tctttttaat ttgcgagttt attgggcttg
       61 ttttctgttt tctagggagt aggttagtgg aaaagaaaaa gggccgaatt cactcccacg
      121 acctctacag ccgcccctga ggggaagcgg tcagcgtaag tcccggatcc ccgctccgga
      181 gccgcctcgt gggagcgggg caaggagatc caggaggggt ctcgaatctg ccatggcgaa
      241 ccggcgagtg gggcgaggct gctgggaagt gagcccgacc gagcggaggc cgcccgcggg
      301 gctgcggggc cccgcggccg aggaggaggc gtcttccccg ccggtcctgt ctctcagcca
      361 cttctgcagg tctcctttcc tttgcttcgg ggacgttctc ctgggagcct cacggacgct
      421 gtctctggcc ctagacaacc ctaacgagga ggtggcagaa gtgaagatct cccacttccc
      481 ggccgcggac ctgggcttca gtgtgtcgca gcgctgtttc gtgttgcagc ctaaagagaa
      541 aattgttatt tctgttaact ggacaccact caaagaaggc cgagtaagag agattatgac
      601 atttcttgta aatgatgttc tgaaacacca agctatatta ctaggaaatg cagaagagca
      661 gaaaaagaaa aagaggagtc tttgggatac cattaaaaag aagaaaattt cagcctctac
      721 aagtcacaac agaagggttt caaatattca gaatgttaat aaaacattta gtgtttccca
      781 aaaagttgac agagttagga gcccactaca agcttgtgaa aacttggcta tgaatgaagg
      841 cggtccccca acagaaaaca attctttaat acttgaagaa aataaaatac ccatatcacc
      901 tattagccct gctttcaatg aatgccatgg tgcaacttgc ttgccactct ctgtacgtcg
      961 atctactacc tactcatctc ttcatgcatc agaaaatagg gaactattaa atgtacacag
     1021 tgccaacgtt tcaaaagttt cttttaatga gaaagctgta actgaaactt cctttaattc
     1081 cgtaaatgtt aatggccaaa gaggagagaa tagtaaactt agtcttaccc ccaactgttc
     1141 ttcaactttg aacattacac aaagccaaat acattttcta agtccagatt cttttgtaaa
     1201 taatagtcat ggagctaata atgaactaga attagtaaca tgtctttcat cagatatgtt
     1261 tatgaaagat aattcacagc ctgtgcattt ggaatcaaca attgcacatg aaatttatca
     1321 gaaaatttta agtccagatt ctttcataaa agataattat ggactaaatc aggatctaga
     1381 atcagagtca gttaatccta ttttatcccc taatcaattt ttaaaagata acatggcata
     1441 tatgtgtaca tctcagcaaa catgtaaagt accattatca aatgaaaatt ctcaagtccc
     1501 acagtctcct gaagattgga gaaaaagtga agtttcgcca cgtattcctg aatgtcaggg
     1561 ttcaaaatct cccaaagcta tttttgaaga actagtagaa atgaagtcaa attactacag
     1621 ttttataaaa caaaataatc ctaaattttc tgcagttcag gatatttcta gtcatagcca
     1681 caataaacaa cctaagagac gtccaatact ttctgccact gttactaaaa ggaaggccac
     1741 ctgtaccaga gaaaaccaaa ctgagattaa taaaccaaaa gcaaaaagat gtctcaacag
     1801 tgcagtgggt gaacatgaaa aagtaataaa taatcaaaag gaaaaagaag attttcattc
     1861 ttatcttcca attatagatc caatattaag taaatctaag agttataaaa acgaggtaac
     1921 accctcttcg acaacagctt cagttgctcg gaaaagaaag agcgatggaa gcatggaaga
     1981 tgcaaatgtg agagttgcaa ttacagaaca tacagaagtg cgagaaatca aaagaatcca
     2041 tttttctccc tcagagccta aaacatcagc tgttaagaaa acaaaaaatg tgacaacacc
     2101 catctcaaaa cgtattagca acagagagaa attaaacctg aagaagaaaa ctgatttatc
     2161 aatattcaga actccaattt ctaaaacaaa caaaaggaca aaacccatta tcgctgtggc
     2221 acagtccagt ttgaccttca taaaaccatt aaaaacagat attcccagac acccgatgcc
     2281 atttgctgca aaaaacatgt tttatgatga acgctggaag gaaaagcagg aacagggctt
     2341 cacttggtgg ttaaatttta tattaacccc tgatgacttc actgtaaaaa caaatatttc
     2401 tgaagtaaat gctgctactc ttcttttggg aatagagaat caacataaaa taagtgttcc
     2461 tagagcacct acaaaagagg aaatgtctct cagagcttat actgctcggt gtaggttaaa
     2521 cagactacgt cgtgcagcat gccgtttgtt tacttctgaa aaaatggtta aagctattaa
     2581 aaagcttgaa attgaaattg aagctaggcg gttaattgtt cgaaaagata gacacctatg
     2641 gaaagatgtg ggagaacgtc agaaagtcct gaattggctg ttgtcctaca atcctttgtg
     2701 gcttcgaatt ggtctagaga caacttatgg agaactcata tctttggaag ataacagtga
     2761 tgtcacaggg ttggctatgt ttattctgaa tcgcctactt tggaatcctg atatagcagc
     2821 tgagtataga caccccactg ttcctcacct gtatagagat ggtcatgaag aagctttgtc
     2881 caagtttaca ttgaaaaagt tattgttgtt ggtctgtttt cttgattatg ctaaaatttc
     2941 cagactcatt gatcatgatc cttgtctctt ctgtaaagat gccgaattca aggctagtaa
     3001 agaaatcctt ttggcttttt cacgagattt cctaagtggt gaaggtgacc tttcccgtca
     3061 ccttggctta ttgggattac ctgttaacca tgttcagaca ccatttgatg aatttgattt
     3121 tgccgttaca aatcttgccg tagacttgca atgtggagtg cgccttgtgc gaaccatgga
     3181 acttctcaca cagaactggg acctctcaaa gaaactcagg attccggcaa taagtcgtct
     3241 tcaaaagatg cacaatgttg acattgttct tcaagttctt aaatcacgag gaattgaatt
     3301 aagtgatgag catggaaata caattctatc taaggatatt gtggataggc acagagaaaa
     3361 aactctcagg ttgctttgga aaatagcgtt tgcttttcag gtggatattt cccttaactt
     3421 agatcaatta aaggaagaaa ttgcctttct aaaacacaca aagagtataa agaaaacaat
     3481 atctctacta tcatgccatt ctgatgatct tattaataag aaaaaaggca aaagggatag
     3541 tggttccttt gaacaatata gtgaaaacat aaagttattg atggattggg taaatgctgt
     3601 ttgtgccttc tataataaaa aggtggagaa ttttacagtg tctttctcag acggccgtgt
     3661 gttatgttac ctgatccacc attaccatcc ttgctatgtg ccatttgacg ctatatgtca
     3721 gcgtactact caaactgtgg aatgtacgca aactggttca gtggtattaa attcatcatc
     3781 tgaatctgat gacagttctc tggatatgtc tcttaaagca tttgatcatg aaaatacttc
     3841 agagctatac aaagagctcc tagaaaatga aaagaaaaat tttcacttgg ttaggtctgc
     3901 agttagagac cttggtggaa tacctgctat gattaatcat tcagatatgt caaatacaat
     3961 tccagatgaa aaggtggtta ttacctattt gtcatttctt tgtgcaaggc ttttggatct
     4021 tcgtaaagaa ataagagctg ctcgactcat acaaacaaca tggagaaaat ataaactaaa
     4081 aacagatctc aaacgccatc aggagagaga gaaagctgca agaattattc aattggctgt
     4141 aatcaatttt ctagcaaaac aaagattgag aaaaagagtt aatgcagcac tcgtcattca
     4201 gaaatattgg cgaagagtct tagcacagag aaaattatta atgttaaaaa aggaaaagct
     4261 ggaaaaagtt caaaataaag cagcatcact tattcaggga tattggagaa gatattccac
     4321 tagacaaaga tttctgaaat tgaaatatta ttcaatcatc ctgcaatcta ggataagaat
     4381 gataattgct gttacatctt ataaacgata tctttgggct acagttacaa ttcagaggca
     4441 ttggcgtgct tatttaagaa gaaaacaaga tcaacaaaga tatgaaatgc taaaatcatc
     4501 aactcttata atccaatcta tgttcagaaa atggaagcaa cgtaaaatgc aatcacaagt
     4561 aaaagctaca gtaatattgc aaagagcttt tagagaatgg catttaagaa aacaagctaa
     4621 agaagaaaat tctgctatta tcatacaatc atggtataga atgcataaag aattacggaa
     4681 atatatttat attagatctt gtgttgttat cattcagaaa agatttcggt gctttcaagc
     4741 ccaaaagtta tataaaagaa gaaaagagtc catactaacc atccagaagt actacaaagc
     4801 atatctgaaa ggaaagattg agcgcaccaa ctatttgcag aaacgagctg cagccattca
     4861 attacaagct gcttttagga gactgaaagc tcataattta tgtagacaaa ttagagctgc
     4921 ttgtgttatt cagtcatact ggagaatgag acaagacaga gttcgatttt taaaccttaa
     4981 gaagactatt atcaaatttc aggcacatgt aagaaaacat caacaacgac agaaatataa
     5041 gaagatgaag aaagcagctg ttataattca gactcatttc cgagcttata tttttgccat
     5101 gaaagttcta gcatcttacc agaaaacacg ctctgctgtc attgtgctgc agtctgcata
     5161 tagagggatg caagccagga aaatgtatat tcacatcctc acatctgtta taaagattca
     5221 atcatattat cgtgcttatg tttctaaaaa ggaatttttg agcctaaaaa atgctacaat
     5281 aaaattgcag tcaactgtta agatgaaaca aacacgtaaa caatatttgc atttaagagc
     5341 agctgcacta tttatccagc aatgttaccg ttccaaaaaa atagctgcac aaaagagaga
     5401 agagtatatg cagatgcggg aatcttgtat caaactgcaa gcatttgtta gaggatacct
     5461 tgtccgaaag cagatgaggt tacaaagaaa agctgttatt tcactacagt cttatttcag
     5521 aatgagaaag gctcggcagt attatctgaa aatgtataaa gcaattattg tcattcagaa
     5581 ttactatcat gcatacaaag cacaggtcaa tcagaggaag aacttcttgc aagtcaaaaa
     5641 agcagctact tgcttgcaag cagcttacag aggttataaa gtacgccagc taatcaaaca
     5701 acaatctata gctgctctta aaattcagtc tgcttttaga ggctataata aaagggtaaa
     5761 atatcaatct gtgcttcaat ctataataaa gattcagaga tggtacaggg cgtacaagac
     5821 tcttcatgat acaagaacac attttttgaa gacaaaggca gctgtgattt ccctccagtc
     5881 tgcttatcgt ggctggaagg ttcggaaaca gattagaagg gaacatcaag ctgccttgaa
     5941 gattcagtct gcttttagaa tggccaaggc ccagaaacag tttagattgt ttaaaacagc
     6001 agcattagtc atccagcaaa atttcagagc atggactgca ggaaggaagc aatgtatgga
     6061 gtatattgaa ctccgtcatg cggtactggt gcttcaatct atgtggaagg gaaaaacact
     6121 gagaagacag cttcaaaggc aacataaatg tgctatcatc atacagtcat actatagaat
     6181 gcatgtgcaa caaaagaagt ggaaaatcat gaaaaaagct gctcttctga ttcaaaagta
     6241 ttatagggct tacagtattg gaagagaaca gaatcattta tatttgaaaa caaaagcagc
     6301 tgtagtaact ttacagtcag cttatcgtgg tatgaaagtg agaaaaagaa taaaggattg
     6361 caacaaagca gcagtcacta tacagtctaa atacagagct tacaaaacca aaaagaaata
     6421 tgcaacctat agagcttcag ctattataat tcagagatgg tatcgaggta ttaaaattac
     6481 aaaccatcag cataaggagt atcttaattt gaagaagaca gcaattaaaa tccaatctgt
     6541 ttatagaggt attagagtta gaagacatat tcaacacatg cacagggcag ccacttttat
     6601 taaagccatg tttaaaatgc atcagtcaag aataagttac catacaatga gaaaagcagc
     6661 tattgttatt caagtaagat gtagagcata ttatcaaggt aaaatgcagc gtgaaaagta
     6721 cctgacaatt ttgaaagctg ttaaagtcct tcaggcaagt tttagaggag taagagttag
     6781 acggactctt agaaagatgc agactgcagc aacactcatt cagtcaaact acagaagata
     6841 cagacagcaa acatacttta ataagttaaa gaaaataaca aaaacagtac agcaaagata
     6901 ctgggcaatg aaagaaagaa acatacaatt tcaaaggtat aacaaactga ggcattctgt
     6961 aatatacatt caggctattt ttaggggaaa gaaagctaga agacatttaa aaatgatgca
     7021 tatagccgca actctcattc agaggagatt tagaactcta atgatgagaa gaagattcct
     7081 ctctctcaag aaaactgcta ttttgattca gagaaaatat cgggcacatc tttgtacaaa
     7141 gcatcactta cagttccttc aggtacaaaa tgcagttatt aaaatccagt catcatacag
     7201 aagatggatg ataaggaaaa ggatgcgaga gatgcacagg gctgctactt tcatccagtc
     7261 tactttcaga atgcacagat tacatatgag atatcaggct ttgaaacagg cctccgttgt
     7321 gatccaacag caataccaag caaatagagc tgcaaaactg cagaggcagc attatctcag
     7381 acaaagacac tctgctgtga tccttcaggc tgcattcagg ggtatgaaaa ctagaagaca
     7441 tttgaagagt atgcattcct ctgcaaccct tattcagagt aggtttagat cattactggt
     7501 gaggagaaga ttcatttccc tcaaaaaagc tactattttt gttcagagga aatatcgagc
     7561 caccatttgt gccaaacata aattgtacca attcttgcac ttaagaaagg cagccattac
     7621 aatacagtca tcttacagaa gactgatggt aaagaagaag ttacaagaaa tgcaaagggc
     7681 tgcagttctc attcaggcta ctttcaggat gtacagaaca tatattacat ttcagacttg
     7741 gaaacatgct tcaattctaa ttcagcaaca ttatcgaaca tatagagctg caaaattaca
     7801 aagagaaaat tatatcagac aatggcattc tgctgtggtt attcaggctg catataaagg
     7861 aatgaaagca agacaacttt taagggaaaa acacaaagct tctatcgtaa tacaaagcac
     7921 ctacagaatg tataggcagt attgtttcta ccaaaagctt cagtgggcta caaaaatcat
     7981 acaagaaaaa tatagagcaa ataaaaagaa acagaaagta tttcaacaca atgaacttaa
     8041 gaaagagact tgtgttcagg caggttttca ggacatgaac ataaaaaaac agattcagga
     8101 acagcaccag gctgccatta ttattcagaa gcattgtaaa gcctttaaaa taaggaagca
     8161 ttatctccac cttagagcaa cagtagtttc tattcaaaga agatacagaa aactaactgc
     8221 agtgcgtacc caagcagtta tttgtataca gtcttattac agaggcttta aagtacgaaa
     8281 ggatattcaa aatatgcacc gggctgccac actaattcag tcattctatc gaatgcacag
     8341 ggccaaagtt gattatgaaa caaagaaaac tgcaattgtg gttatacaga attattatag
     8401 gttgtatgtt agagtaaaaa cagaaagaaa aaacttttta gcagttcaga aatctgtacg
     8461 aactattcag gctgctttta gaggcatgaa agttagacaa aaattgaaaa atgtatcaga
     8521 ggaaaagatg gcagccattg ttaaccaatc tgcactctgc tgttacagaa gtaaaactca
     8581 gtatgaagct gttcaaagtg aaggtgttat gattcaagag tggtataaag cttctggcct
     8641 tgcttgttca caggaagcag agtatcattc tcaaagtagg gctgcagtaa caattcaaaa
     8701 agctttttgt agaatggtca caagaaaact ggaaacacag aaatgtgctg ccctacggat
     8761 tcagttcttc cttcagatgg ctgtgtatcg gagaagattt gttcagcaga aaagagctgc
     8821 tatcacttta cagcattatt ttaggacgtg gcaaaccaga aaacagtttt tactatatag
     8881 aaaagcagca gtggttttac aaaatcacta cagagcattt ctgtctgcaa aacatcaaag
     8941 acaagtctat ttacagatca gaagcagtgt tatcattatt caagctagaa gtaaaggatt
     9001 tatacagaaa cggaagtttc aggaaattaa aaatagcacc ataaaaattc aggctatgtg
     9061 gaggagatat agagccaaga aatatttatg taaagtgaaa gctgcctgca agattcaagc
     9121 ctggtataga tgttggagag cacacaaaga atatctagct atattaaaag ctgttaaaat
     9181 tattcaaggt tgcttctata ccaaactaga gagaacacgg tttttgaatg tgagagcatc
     9241 agcaattatc attcagagaa aatggagagc tatacttcct gcaaagatag ctcatgaaca
     9301 cttcttaatg ataaaaagac atcgagctgc ttgtttgatc caagcacatt atagaggata
     9361 taaaggaagg caggtctttc ttcggcagaa atctgctgct ttgatcatac aaaaatatat
     9421 acgagccagg gaggctggaa agcatgaaag gataaaatat attgaattta aaaaatctac
     9481 agttatccta caagcactgg tgcgtggttg gctagtacga aaaagatttt tagaacagag
     9541 agccaaaatt cgacttcttc acttcactgc agctgcatat tatcacctga atgctgttag
     9601 aattcaaaga gcctataaac tttacctggc tgtgaagaat gctaacaagc aggttaattc
     9661 agtcatctgt attcagagat ggtttcgagc aagattacaa gaaaagagat ttattcagaa
     9721 atatcatagc atcaaaaaga ttgagcatga aggtcaagaa tgtctgagcc agcgaaatag
     9781 ggctgcatca gtaatacaga aagcagtgcg ccattttctc ctccgtaaaa agcaggaaaa
     9841 attcactagt ggaatcatta aaattcaggc attatggaga ggctattctt ggaggaagaa
     9901 aaatgattgt acaaaaatta aagctatacg actaagtctt caagttgtta atagggagat
     9961 tcgagaagaa aacaaactct acaaaagaac tgcacttgca cttcattacc ttttgacata
    10021 taagcacctt tctgccattc ttgaggcctt aaaacaccta gaggtagtta ctagattgtc
    10081 tccactttgt tgtgagaaca tggcccagag tggagcaatt tctaaaatat ttgttttgat
    10141 ccgaagttgt aatcgcagta ttccttgtat ggaagtcatc agatatgctg tgcaagtctt
    10201 gcttaatgta tctaagtatg agaaaactac ttcagcagtt tatgatgtag aaaattgtat
    10261 agatatacta ttggagcttt tgcagatata ccgagaaaag cctggtaata aagttgcaga
    10321 caaaggcgga agcattttta caaaaacttg ttgtttgttg gctattttac tgaagacaac
    10381 aaatagagcc tctgatgtac gaagtaggtc caaagttgtt gaccgtattt acagtctcta
    10441 caaacttaca gctcataaac ataaaatgaa tactgaaaga atactttaca agcaaaagaa
    10501 gaattcttct ataagcattc cttttatccc agaaacacct gtaaggacca gaatagtttc
    10561 aagacttaag ccagattggg ttttgagaag agataacatg gaagaaatca caaatcccct
    10621 gcaagctatt caaatggtga tggatacgct tggcattcct tattagtaaa tgtaaacatt
    10681 ttcagtatgt atagtgtaaa gaaatattaa agccaatcat gagtacgtaa agtgattttt
    10741 gctctccgtg tacaactttt aaaatctgac tttgttttaa aaaaacataa actgttcatt
    10801 acattcttca tttttatcat ttatagtttt atgcatgtaa taaactaata tgtcataaga
    10861 tga
//
