LOCUS       NM_018151              14662 bp    mRNA    linear   PRI 23-APR-2024
DEFINITION  Homo sapiens replication timing regulatory factor 1 (RIF1),
            transcript variant 1, mRNA.
ACCESSION   NM_018151
VERSION     NM_018151.5
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 14662)
  AUTHORS   Kordowitzki,P., Graczyk,S., Mechsner,S. and Sehouli,J.
  TITLE     Shedding Light on the Interaction Between Rif1 and Telomeres in
            Ovarian Cancer
  JOURNAL   Aging Dis 15 (2), 535-545 (2024)
   PUBMED   37548940
  REMARK    GeneRIF: Shedding Light on the Interaction Between Rif1 and
            Telomeres in Ovarian Cancer.
            Review article
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 14662)
  AUTHORS   Harvey-Jones,E., Raghunandan,M., Robbez-Masson,L.,
            Magraner-Pardo,L., Alaguthurai,T., Yablonovitch,A., Yen,J.,
            Xiao,H., Brough,R., Frankum,J., Song,F., Yeung,J., Savy,T.,
            Gulati,A., Alexander,J., Kemp,H., Starling,C., Konde,A., Marlow,R.,
            Cheang,M., Proszek,P., Hubank,M., Cai,M., Trendell,J., Lu,R.,
            Liccardo,R., Ravindran,N., Llop-Guevara,A., Rodriguez,O.,
            Balmana,J., Lukashchuk,N., Dorschner,M., Drusbosky,L., Roxanis,I.,
            Serra,V., Haider,S., Pettitt,S.J., Lord,C.J. and Tutt,A.N.J.
  TITLE     Longitudinal profiling identifies co-occurring BRCA1/2 reversions,
            TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant
            advanced breast cancer
  JOURNAL   Ann Oncol 35 (4), 364-380 (2024)
   PUBMED   38244928
  REMARK    GeneRIF: Longitudinal profiling identifies co-occurring BRCA1/2
            reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP
            inhibitor-resistant advanced breast cancer.
REFERENCE   3  (bases 1 to 14662)
  AUTHORS   Yao,W., Wang,Y., Huang,M., Zhou,J., Zheng,R., Jin,C. and Zhang,Y.
  TITLE     MiR-30a-5p Enhances Cisplatin Sensitivity by Downregulating RIF1 in
            Ovarian Cancer
  JOURNAL   Ann Clin Lab Sci 53 (3), 418-426 (2023)
   PUBMED   37437929
  REMARK    GeneRIF: MiR-30a-5p Enhances Cisplatin Sensitivity by
            Downregulating RIF1 in Ovarian Cancer.
REFERENCE   4  (bases 1 to 14662)
  AUTHORS   Kong,N., Liu,Z. and Chan,Y.W.
  TITLE     RIF1 suppresses the formation of single-stranded ultrafine anaphase
            bridges via protein phosphatase 1
  JOURNAL   Cell Rep 42 (2), 112032 (2023)
   PUBMED   36719798
  REMARK    GeneRIF: RIF1 suppresses the formation of single-stranded ultrafine
            anaphase bridges via protein phosphatase 1.
REFERENCE   5  (bases 1 to 14662)
  AUTHORS   Tang,M., Chen,Z., Wang,C., Feng,X., Lee,N., Huang,M., Zhang,H.,
            Li,S., Xiong,Y. and Chen,J.
  TITLE     Histone chaperone ASF1 acts with RIF1 to promote DNA end joining in
            BRCA1-deficient cells
  JOURNAL   J Biol Chem 298 (6), 101979 (2022)
   PUBMED   35472331
  REMARK    GeneRIF: Histone chaperone ASF1 acts with RIF1 to promote DNA end
            joining in BRCA1-deficient cells.
REFERENCE   6  (bases 1 to 14662)
  AUTHORS   Esteves,S.L., Domingues,S.C., da Cruz e Silva,O.A., Fardilha,M. and
            da Cruz e Silva,E.F.
  TITLE     Protein phosphatase 1alpha interacting proteins in the human brain
  JOURNAL   OMICS 16 (1-2), 3-17 (2012)
   PUBMED   22321011
REFERENCE   7  (bases 1 to 14662)
  AUTHORS   Shimada,M., Miyagawa,T., Kawashima,M., Tanaka,S., Honda,Y.,
            Honda,M. and Tokunaga,K.
  TITLE     An approach based on a genome-wide association study reveals
            candidate loci for narcolepsy
  JOURNAL   Hum Genet 128 (4), 433-441 (2010)
   PUBMED   20677014
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   8  (bases 1 to 14662)
  AUTHORS   Wang,H., Zhao,A., Chen,L., Zhong,X., Liao,J., Gao,M., Cai,M.,
            Lee,D.H., Li,J., Chowdhury,D., Yang,Y.G., Pfeifer,G.P., Yen,Y. and
            Xu,X.
  TITLE     Human RIF1 encodes an anti-apoptotic factor required for DNA repair
  JOURNAL   Carcinogenesis 30 (8), 1314-1319 (2009)
   PUBMED   19483192
  REMARK    GeneRIF: High RIF1 expression is associated with breast tumors.
REFERENCE   9  (bases 1 to 14662)
  AUTHORS   Xu,L. and Blackburn,E.H.
  TITLE     Human Rif1 protein binds aberrant telomeres and aligns along
            anaphase midzone microtubules
  JOURNAL   J Cell Biol 167 (5), 819-830 (2004)
   PUBMED   15583028
  REMARK    GeneRIF: In telophase, hRif1 localized to chromosomes, and in
            interphase, it was intranuclear. These results define a novel
            subcellular localization behavior for hRif1 during the cell cycle.
REFERENCE   10 (bases 1 to 14662)
  AUTHORS   Silverman,J., Takai,H., Buonomo,S.B., Eisenhaber,F. and de Lange,T.
  TITLE     Human Rif1, ortholog of a yeast telomeric protein, is regulated by
            ATM and 53BP1 and functions in the S-phase checkpoint
  JOURNAL   Genes Dev 18 (17), 2108-2119 (2004)
   PUBMED   15342490
  REMARK    GeneRIF: Rif1 functions in the intra-S-phase checkpoint that serves
            to slow down DNA synthesis when DNA damage has occurred.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AY727913.1, AY584066.1 and
            AC009497.3.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_018151.4.
            
            Summary: This gene encodes a protein that shares homology with the
            yeast teleomere binding protein, Rap1 interacting factor 1. This
            protein localizes to aberrant telomeres may be involved in DNA
            repair. Alternate splicing results in multiple transcript variants.
            [provided by RefSeq, Apr 2010].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript 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 :: AY727913.1, SRR1803614.2216.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000444746.7/ ENSP00000390181.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-142               AY727913.1         20-161
            143-7561            AY584066.1         1-7419
            7562-14662          AC009497.3         53455-60555
FEATURES             Location/Qualifiers
     source          1..14662
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q23.3"
     gene            1..14662
                     /gene="RIF1"
                     /note="replication timing regulatory factor 1"
                     /db_xref="GeneID:55183"
                     /db_xref="HGNC:HGNC:23207"
                     /db_xref="MIM:608952"
     exon            1..132
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            133..246
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     CDS             143..7561
                     /gene="RIF1"
                     /note="isoform 1 is encoded by transcript variant 1;
                     telomere-associated protein RIF1; rap1-interacting factor
                     1 homolog; RAP1 interacting factor homolog"
                     /codon_start=1
                     /product="telomere-associated protein RIF1 isoform 1"
                     /protein_id="NP_060621.3"
                     /db_xref="CCDS:CCDS2194.1"
                     /db_xref="GeneID:55183"
                     /db_xref="HGNC:HGNC:23207"
                     /db_xref="MIM:608952"
                     /translation="MTARGQSPLAPLLETLEDPSASHGGQTDAYLTLTSRMTGEEGKE
                     VITEIEKKLPRLYKVLKTHISSQNSELSSAALQALGFCLYNPKITSELSEANALELLS
                     KLNDTIKNSDKNVRTRALWVISKQTFPSEVVGKMVSSIIDSLEILFNKGETHSAVVDF
                     EALNVIVRLIEQAPIQMGEEAVRWAKLVIPLVVHSAQKVHLRGATALEMGMPLLLQKQ
                     QEIASITEQLMTTKLISELQKLFMSKNETYVLKLWPLFVKLLGRTLHRSGSFINSLLQ
                     LEELGFRSGAPMIKKIAFIAWKSLIDNFALNPDILCSAKRLKLLMQPLSSIHVRTETL
                     ALTKLEVWWYLLMRLGPHLPANFEQVCVPLIQSTISIDSNASPQGNSCHVATSPGLNP
                     MTPVHKGASSPYGAPGTPRMNLSSNLGGMATIPSIQLLGLEMLLHFLLGPEALSFAKQ
                     NKLVLSLEPLEHPLISSPSFFSKHANTLITAVHDSFVAVGKDAPDVVVSAIWKELISL
                     VKSVTESGNKKEKPGSEVLTLLLKSLESIVKSEVFPVSKTLVLMEITIKGLPQKVLGS
                     PAYQVANMDILNGTPALFLIQLIFNNFLECGVSDERFFLSLESLVGCVLSGPTSPLAF
                     SDSVLNVINQNAKQLENKEHLWKMWSVIVTPLTELINQTNEVNQGDALEHNFSAIYGA
                     LTLPVNHIFSEQRFPVATMKTLLRTWSELYRAFARCAALVATAEENLCCEELSSKIMS
                     SLEDEGFSNLLFVDRIIYIITVMVDCIDFSPYNIKYQPKVKSPQRPSDWSKKKNEPLG
                     KLTSLFKLIVKVIYSFHTLSFKEAHSDTLFTIGNSITGIISSVLGHISLPSMIRKIFA
                     TLTRPLALFYENSKLDEVPKVYSCLNNKLEKLLGEIIACLQFSYTGTYDSELLEQLSP
                     LLCIIFLHKNKQIRKQSAQFWNATFAKVMMLVYPEELKPVLTQAKQKFLLLLPGLETV
                     EMMEESSGPYSDGTENSQLNVKISGMERKSNGKRDSFLAQTKNKKENMKPAAKLKLES
                     SSLKVKGEILLEEEKSTDFVFIPPEGKDAKERILTDHQKEVLKTKRCDIPAMYNNLDV
                     SQDTLFTQYSQEEPMEIPTLTRKPKEDSKMMITEEQMDSDIVIPQDVTEDCGMAEHLE
                     KSSLSNNECGSLDKTSPEMSNSNNDERKKALISSRKTSTECASSTENSFVVSSSSVSN
                     TTVAGTPPYPTSRRQTFITLEKFDGSENRPFSPSPLNNISSTVTVKNNQETMIKTDFL
                     PKAKQREGTFSKSDSEKIVNGTKRSSRRAGKAEQTGNKRSKPLMRSEPEKNTEESVEG
                     IVVLENNPPGLLNQTECVSDNQVHLSESTMEHDNTKLKAATVENAVLLETNTVEEKNV
                     EINLESKENTPPVVISADQMVNEDSQVQITPNQKTLRRSSRRRSEVVESTTESQDKEN
                     SHQKKERRKEEEKPLQKSPLHIKDDVLPKQKLIAEQTLQENLIEKGSNLHEKTLGETS
                     ANAETEQNKKKADPENIKSEGDGTQDIVDKSSEKLVRGRTRYQTRRASQGLLSSIENS
                     ESDSSEAKEEGSRKKRSGKWKNKSNESVDIQDQEEKVVKQECIKAENQSHDYKATSEE
                     DVSIKSPICEKQDESNTVICQDSTVTSDLLQVPDDLPNVCEEKNETSKYAEYSFTSLP
                     VPESNLRTRNAIKRLHKRDSFDNCSLGESSKIGISDISSLSEKTFQTLECQHKRSRRV
                     RRSKGCDCCGEKSQPQEKSLIGLKNTENNDVEISETKKADVQAPVSPSETSQANPYSE
                     GQFLDEHHSVNFHLGLKEDNDTINDSLIVSETKSKENTMQESLPSGIVNFREEICDMD
                     SSEAMSLESQESPNENFKTVGPCLGDSKNVSQESLETKEEKPEETPKMELSLENVTVE
                     GNACKVTESNLEKAKTMELNVGNEASFHGQERTKTGISEEAAIEENKRNDDSEADTAK
                     LNAKEVATEEFNSDISLSDNTTPVKLNAQTEISEQTAAGELDGGNDVSDLHSSEETNT
                     KMKNNEEMMIGEAMAETGHDGETENEGITTKTSKPDEAETNMLTAEMDNFVCDTVEMS
                     TEEGIIDANKTETNTEYSKSEEKLDNNQMVMESDILQEDHHTSQKVEEPSQCLASGTA
                     ISELIIEDNNASPQKLRELDPSLVSANDSPSGMQTRCVWSPLASPSTSILKRGLKRSQ
                     EDEISSPVNKVRRVSFADPIYQAGLADDIDRRCSIVRSHSSNSSPIGKSVKTSPTTQS
                     KHNTTSAKGFLSPGSRSPKFKSSKKCLISEMAKESIPCPTESVYPPLVNCVAPVDIIL
                     PQITSNMWARGLGQLIRAKNIKTIGDLSTLTASEIKTLPIRSPKVSNVKKALRIYHEQ
                     QVKTRGLEEIPVFDISEKTVNGIENKSLSPDEERLVSDIIDPVALEIPLSKNLLAQIS
                     ALALQLDSEDLHNYSGSQLFEMHEKLSCMANSVIKNLQSRWRSPSHENSI"
     exon            247..325
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            326..422
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            423..550
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            551..645
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            646..835
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            836..928
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            929..1067
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            1068..1219
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            1220..1337
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            1338..1514
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            1515..1625
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            1626..1688
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            1689..1789
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            1790..1876
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            1877..1947
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            1948..2128
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            2129..2236
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            2237..2386
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            2387..2486
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            2487..2751
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            2752..2794
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            2795..2997
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            2998..3097
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            3098..3217
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            3218..3369
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            3370..3450
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            3451..3505
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            3506..6742
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            6743..6889
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            6890..6967
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            6968..7083
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            7084..7237
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            7238..7346
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     exon            7347..14662
                     /gene="RIF1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      9810..9815
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RIF1"
                     /note="hexamer: AACAAA"
     polyA_site      9833
                     /gene="RIF1"
     regulatory      14642..14647
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RIF1"
                     /note="hexamer: AATAAA"
     polyA_site      14662
                     /gene="RIF1"
                     /note="major polyA site"
ORIGIN      
        1 agccgccatc ttggtctagg agggagcgcg ccgcacgcgt gagtaaacag ccggagctgg
       61 gaaagtcgag ctctggcagc gtctgggtgc tgaggggcag aggcggagag aaccctgtcc
      121 tgatcttcct agggtggccg acatgacggc caggggtcag agccccctcg cgccgctgtt
      181 ggagactttg gaagaccctt ctgcctccca tggagggcag actgacgctt acctgactct
      241 gaccagtcgt atgactggag aagaaggaaa agaagtaatt acagaaattg agaaaaaact
      301 tcctcggctg tacaaagttt taaagactca catttccagt caaaactcgg agctgagtag
      361 tgctgctcta caagccctgg ggttttgctt atataatccc aaaattacct cagaattatc
      421 agaggcaaat gctctagaat tgctttcaaa attgaatgat accattaaga attcagacaa
      481 aaatgtacgt actagagcac tttgggtgat atctaagcag acatttccct ctgaagtggt
      541 tggcaaaatg gtatccagta taattgattc attagaaata ctgtttaaca aaggagagac
      601 gcattctgct gttgttgatt ttgaagcatt aaatgttatc gtaaggctaa ttgaacaagc
      661 cccaattcaa atgggagaag aggcagtgag gtgggcaaaa ctggtcatac ctttagtggt
      721 tcattcagca caaaaggtac atttgcgggg agcaactgct ctggagatgg gaatgccatt
      781 attgcttcag aaacagcaag aaatagcatc tattacggag cagcttatga ctactaaatt
      841 aatctcagaa cttcagaagc tatttatgag taaaaatgag acttacgtgt taaaattatg
      901 gcctttgttt gtcaaactac ttggaaggac cttgcatcga agtgggagtt tcatcaattc
      961 tctcttgcaa ctagaagaac ttggatttcg tagtggagca cccatgatta aaaagatagc
     1021 ttttattgct tggaagagtt taatagataa ttttgcttta aatccagata tactatgtag
     1081 tgcaaaaaga ctcaagttgt taatgcagcc tttgagttcc atccatgtga gaacagaaac
     1141 tctagcatta acaaaactag aagtctggtg gtatttactg atgagacttg gacctcatct
     1201 tcctgctaat tttgaacagg tttgtgtgcc tctgattcaa agtacaataa gcattgattc
     1261 taatgcctca cctcagggca attcgtgtca tgtagctaca tctccaggtt taaatcctat
     1321 gactcctgta cacaaaggtg cttcctcccc gtacggagcc ccgggaactc cccgaatgaa
     1381 cctgagttcg aatttaggtg gaatggccac aatcccatcc attcaacttt tgggacttga
     1441 aatgttgctt catttcttgt tgggtccaga agccttgagt tttgctaagc aaaataaact
     1501 tgtgctgagc ttagagccat tggaacatcc gttaatcagc agcccttcct ttttttccaa
     1561 acatgcaaat acacttatca ctgctgttca tgatagcttt gttgcagttg gaaaagatgc
     1621 ccccgatgtg gttgtcagtg ctatctggaa ggagctaatt agcttggtga agtcagttac
     1681 tgaatcaggt aacaaaaaag agaaaccagg ttctgaagtt ttgactctct tattaaagtc
     1741 tttggaaagc atagtaaagt ctgaagtatt tcctgtatca aaaacgctgg tcctcatgga
     1801 aattacaatt aaaggacttc ctcagaaagt attaggttca ccagcatatc aggttgctaa
     1861 tatggatatt cttaatggaa ctccagcttt gttcttaatt caattaattt tcaacaattt
     1921 cttggaatgt ggtgtatcag atgaaaggtt ctttctcagt ttggaatcac ttgtaggctg
     1981 tgttctttct ggtccaactt caccactagc tttcagtgac tcagttttaa atgttattaa
     2041 tcaaaatgca aagcagttgg aaaataagga gcatctctgg aaaatgtgga gtgttatagt
     2101 caccccatta actgaattga ttaatcagac caatgaagta aatcaaggtg atgccttaga
     2161 acataatttt agtgccatct atggtgcatt gactttacca gtaaaccaca ttttttcaga
     2221 acagagattt ccagtggcca ccatgaagac tttgcttaga acttggtcag aattatatag
     2281 agcatttgct cgttgtgctg ctttggtggc aacagcagaa gagaacttgt gctgtgagga
     2341 actttcttcc aagataatgt ccagtttgga agatgaaggc ttttctaatt tgttgttcgt
     2401 ggatagaatt atttatatta ttactgtaat ggttgattgc attgacttct caccatataa
     2461 tattaaatat cagcccaaag ttaaatcacc acagagacct tcagattggt ccaaaaagaa
     2521 gaatgagccc ctagggaaat tgacttcttt atttaaactt attgtgaaag tgatctattc
     2581 tttccacaca ctgagcttca aggaagcaca ttctgatacc ctcttcacta ttggcaactc
     2641 aatcaccggc attatttcca gtgtacttgg gcatatttct ttgccttcta tgatccgaaa
     2701 aatatttgca actttaacaa gacctctggc attattttat gaaaactcaa agcttgatga
     2761 agttcctaaa gtatatagtt gtctgaacaa caagttagaa aagctactgg gagaaattat
     2821 tgcttgtctg caattcagct acaccggaac ttatgatagt gaacttcttg aacaactctc
     2881 cccactatta tgcataatat ttctgcacaa gaataaacag attcgaaaac agagtgctca
     2941 gttctggaat gccacttttg ccaaagtgat gatgttggtt tatcctgaag agttaaaacc
     3001 agtactaaca caagccaaac aaaaatttct gctcctgttg cctggtttgg aaactgttga
     3061 aatgatggag gaatccagtg gaccatattc tgatggaaca gaaaattcac aactaaatgt
     3121 gaagataagt ggcatggaga gaaaatcaaa tggaaaaaga gattcatttt tggcacaaac
     3181 aaagaataaa aaagaaaata tgaaaccagc agccaaactg aaacttgaat cttcgtcttt
     3241 aaaagtaaag ggtgaaattc ttttggaaga ggaaaagtct actgactttg tgtttatacc
     3301 tccagaagga aaagatgcaa aggaaagaat attaactgat catcaaaaag aagttctcaa
     3361 aacaaagcgg tgtgatattc ctgccatgta taataatctg gatgtttccc aagatacctt
     3421 atttactcag tatagtcagg aagagcctat ggaaattcct actttaacca gaaaaccaaa
     3481 ggaggattct aagatgatga ttacggagga gcaaatggac agtgacattg tcattcctca
     3541 agatgtcacg gaagactgtg gtatggctga acatcttgaa aagtcctccc tttcgaataa
     3601 tgagtgtggt tctcttgaca aaaccagtcc agaaatgtca aacagtaata atgatgaaag
     3661 aaaaaaagct ttaatttcat caaggaaaac atcaactgaa tgtgcatcta gtacagaaaa
     3721 ttctttcgtt gtcagcagta gttcagtttc taataccact gttgctggaa ctcccccata
     3781 ccctacaagt cggaggcaaa cctttattac tttggagaag tttgatggtt cagaaaatag
     3841 accttttagt ccatccccct tgaataatat ttcatcaact gttacagtga aaaataacca
     3901 ggaaaccatg attaaaacag attttctacc aaaagcaaag caaagagaag ggactttttc
     3961 aaaatctgat tctgaaaaaa tagtgaatgg aactaagaga tcaagccgga gagctggtaa
     4021 agctgaacaa acagggaata aaaggtctaa gcccttaatg agatctgagc cggagaaaaa
     4081 tactgaggaa tctgttgaag gcattgtagt cttagaaaat aacccacctg gtttgcttaa
     4141 tcaaacagaa tgtgtgtcag ataatcaggt tcatctttct gaatctacaa tggagcatga
     4201 caatacaaag cttaaagcag caacagtgga aaatgctgta ttattggaaa ctaatactgt
     4261 agaggagaaa aatgtagaaa ttaatttgga atccaaagag aatacacccc cagtagtaat
     4321 atcagcagat caaatggtaa atgaggatag tcaggttcag ataactccaa atcagaaaac
     4381 ccttagacgg tcttcaaggc gacgttcaga agtagtagag tctaccactg aaagccaaga
     4441 taaggaaaat agtcatcaaa aaaaggaacg acgtaaggaa gaagaaaaac ctcttcagaa
     4501 gagtccattg catataaaag atgatgtgtt acctaaacaa aaactgattg ctgaacaaac
     4561 tctacaggag aatttaattg agaaaggaag taatttacat gagaagactc ttggggaaac
     4621 tagtgctaat gcagaaactg aacaaaataa aaaaaaggca gaccctgaga acattaagtc
     4681 tgagggggat ggtacccagg acattgtaga taagtcctct gagaaactag tcagaggccg
     4741 aacacggtat caaactagaa gagcatctca gggtttgctt tccagcattg aaaactcaga
     4801 atctgatagt tcggaggcaa aagaagaagg ttctaggaag aagagatctg gaaaatggaa
     4861 aaacaaaagc aatgaaagtg ttgacattca agatcaagaa gagaaagtgg tgaaacagga
     4921 atgtataaaa gctgaaaatc agtcacatga ttataaagca acttctgaag aagatgtaag
     4981 cataaaatct ccgatttgcg aaaaacaaga tgaaagtaat actgtaatat gtcaggattc
     5041 tacagtaact tcagatttgt tgcaagttcc tgatgattta ccaaatgtgt gtgaggaaaa
     5101 aaatgaaact agcaaatatg cagaatattc ctttacaagt ctacctgtgc cagaatcaaa
     5161 tctaaggact agaaatgcca ttaagagatt acataagcga gactcttttg ataattgtag
     5221 tttgggagaa tcctcaaaaa tagggatatc agatatttct tcgctttcag aaaaaacttt
     5281 tcaaacactt gaatgccaac acaagagaag taggagggtg aggagatcta aaggttgtga
     5341 ttgctgtggg gaaaaatcac aacctcagga aaagtcactc attgggttaa agaatacaga
     5401 aaataatgac gtagagatta gtgaaacaaa aaaggcagat gtgcaagcac ctgtaagccc
     5461 atcagaaact tctcaagcta atccatattc tgaaggacaa tttttagatg aacatcatag
     5521 tgtgaatttt catttgggtc tcaaagagga taatgatact attaatgatt cattaattgt
     5581 ttctgaaacc aaatcaaaag aaaacactat gcaagaatct cttccttctg gaatagtaaa
     5641 ctttagagag gaaatttgtg atatggattc tagtgaagca atgtctcttg aaagccagga
     5701 gtcacctaat gaaaatttta aaactgttgg cccgtgttta ggagactcga aaaatgtttc
     5761 acaggaatct ttggagacaa aagaagaaaa accagaagaa accccaaaaa tggaactgag
     5821 tctagagaat gttactgttg aaggaaatgc atgtaaagta acagaatcca atctagagaa
     5881 agcaaaaact atggaattga atgtaggaaa tgaagctagc tttcatggac aagagagaac
     5941 caaaactggt atttctgaag aagcagcaat agaagaaaat aaaagaaatg atgactctga
     6001 agcagacaca gctaaactga atgccaaaga agtagcaact gaggaattta attcagatat
     6061 tagtctttct gataatacta cacctgtaaa attgaatgct caaactgaga tttctgaaca
     6121 aacagcagct ggggaactag atggaggaaa tgatgtatct gatctacact catctgaaga
     6181 aacgaatacc aaaatgaaaa ataatgaaga aatgatgatc ggcgaggcaa tggctgaaac
     6241 tggccatgat ggtgaaacag agaatgaggg cataactacc aaaacctcaa agcctgatga
     6301 agctgaaaca aacatgttga ctgcagaaat ggacaacttt gtttgtgaca cagttgaaat
     6361 gagcactgaa gaaggaatca ttgacgctaa taaaactgaa acaaatactg agtatagtaa
     6421 atctgaagaa aaattagata acaatcaaat ggtaatggaa agtgatattt tacaggaaga
     6481 tcaccatact tcacagaaag tggaggaacc atcacagtgt ctggcatctg gaacagctat
     6541 ctctgagcta ataatagaag acaataatgc atctcctcaa aaactaaggg aacttgatcc
     6601 ttcacttgtg tcagcaaatg acagtcctag tggcatgcag acacgctgtg tctggtctcc
     6661 tttggcttct ccgtctacga gcattttaaa gagaggacta aaaagatccc aagaagatga
     6721 aatctcatca cctgttaata aggttcgccg tgtctccttt gcagatccaa tataccaagc
     6781 aggattggca gatgacattg atagacggtg ctctattgtt aggtcccatt cttccaatag
     6841 ttctcccata ggaaaaagtg ttaaaacttc tcctactaca caatctaagc ataataccac
     6901 ttcagccaaa ggatttctgt ccccaggatc acgtagccct aaatttaaga gctcaaagaa
     6961 gtgtttaatt tcagaaatgg ccaaagaatc cataccatgc ccaacagaaa gtgtttaccc
     7021 accattggtg aactgtgtgg caccagttga catcatttta cctcagatta catcaaacat
     7081 gtgggcaaga ggcctgggac aactcattag agctaagaat ataaaaacta ttggtgattt
     7141 gagtactctt acagcatctg aaataaaaac tcttcctatc cgttctccaa aagtgtccaa
     7201 tgtaaaaaag gctctcagaa tatatcatga gcagcaggtg aagactcgtg gactagaaga
     7261 gattccagtt tttgatattt ctgaaaaaac agtaaatgga atagaaaata aatctttgtc
     7321 acctgatgaa gaaagacttg tctcagatat aattgatcct gttgctttag aaattccatt
     7381 atccaaaaac cttctggcac agattagtgc tcttgctctt cagctggatt cagaagatct
     7441 tcataattat tcaggaagcc aactatttga aatgcacgag aaactaagtt gtatggcaaa
     7501 ctctgtaata aaaaatctac agtcacgttg gagatcacca tcccatgaaa attctattta
     7561 gtattttcag agaaaattga aggttttttt aaacatcact ggatttcttg attgaggaaa
     7621 caagttctga aataatagca caatttcaaa gaagagactc tttgcaaagt tgataacatt
     7681 tcaaaccctg aaggacagtg acttattatg taagttcaat tttgtaagtt cattatgtaa
     7741 gatccttttt tttttcataa tatgtattct tggctgctat gcgtggtttt tcaggaaatt
     7801 taattatctt actgagatgt gaaagcaaaa ctagtaacag aacttacatt ttatttcatg
     7861 ctttcttaaa cccgtgcata ttctggtgaa acatgtaaaa tactttaagt aaaattgaac
     7921 atttttattt gaatttttgc tgaactgata aaggtgttta tatttttgtt tgttggtttg
     7981 tttaattcat gtttgttggg actgaggttt aggaagtttg ttactggtta aaaacctcaa
     8041 atgaaatgcg aaagaatttg aatttttcct gcatatgtca actttggaca gctttcaaga
     8101 aaaatgagaa aagtttcaac ttctggcggt taaaatatta atgcagaatt tactaagatt
     8161 ttattcattt gcattagcaa atattcatgc agcagcagtt gactgaaaat ttattcttat
     8221 gagacgtata gtattcattt ttaaatgcat gattgtacat tatgtataga cgacaatgtt
     8281 tttaatttat aaatttcatt ctttgttaat tgcatgggtt tttctgcagc ttattgtgaa
     8341 taccttggtt ctgttcaata gaaacatttt gtatatatta aatactgaaa tatcagtatc
     8401 gacggtggaa gtgcttcatg ggcttgctgc acatatttgt aggatactgt atctgcaaat
     8461 gcaacaacaa atagttttgt acttggttaa cagtcttagt taaaacatga gtttattttc
     8521 taaaagtatc cagaataagt aaaattatag aaataagaaa atgttacaca actttgctgt
     8581 tcataccctt accttcttac tacttttggt ttggaggagg gtatcaccac tagaaagtgt
     8641 gcctccttaa gatttcttaa aggaaagtta gtttcagtat ttcacagcaa gttggactac
     8701 aaaatctaga gttgatctgc tttttaaacc ttcatttaaa agcaaacttg gaagaaattt
     8761 gaaactgatg tttttaatat atgtctgtgt tgcctaggtt ttcttttttt aaagaggtat
     8821 gtaattaaaa cctttgtaaa atttgccaac taatattagt gcctgacttc ccatatttgt
     8881 ttcatctttt taactgacag tatatctcac ttcttctttg aatagaatga gtgagtgatc
     8941 tcagttttca cattttattc agaagctaat ccctacttag caaggcacac attctacagc
     9001 aagtcataga aagtttaatc cttgtgcctc cttagctctc gtatattcag ggatctctat
     9061 aaaagttggt gtcttttttc atcatcataa attcatcata atcacagata tttttgggtc
     9121 taagatattc atataccaag gatggttttg taaagaattc tgggatcatt gaattaagga
     9181 ttgtggcttg aagtaactaa agaaaaatac taatttcctt aaaaggaatt ataattatga
     9241 tttacatttt acatcattaa tttcccaaat tatatttaac cgtaaggagg tgcacatgag
     9301 tttttagcaa acaggtatga ataagcagct atgtatatgt gtttggggca gaggggagca
     9361 gattacttta acacacttca gaattaaaat cagttcgttt catgactctg tgccttaacg
     9421 tttgtgtgaa ctaaacttgc tgattgaatg aaattcttgg gaagccgaac agtaatagca
     9481 gaaaatgtga ccaaatgagt atcatgtact taaatcactg aattttatat aagcacaagt
     9541 attaatttta aaaacattat agtttaataa agctgcattt aaaaatattt gggagcaaag
     9601 acaagcatgc taaatcttca ttttgctatg gctataagca tatatttttg gcaacttatt
     9661 tgcaatattc ttgccttaaa gtttcctgca aatttccccc ttagtaattc ccgaatagca
     9721 aaacattaat attccatgat tagctctact gtgttgtctc actattaaaa tggaattcgt
     9781 tttttcagat cttttctaat ggttaataaa acaaatgtca gatcataata acactcaaat
     9841 gtgtcttaat tgtcttatgc atatttaaga agaaaaaact agtggcatac aggattgtca
     9901 tgtagtatct tttttttttt ttgagacaca gtcttgctct gttgcctatg ctggagtgca
     9961 atggtgcgat ctcggttcac tgcaagctct gcctcccagg tttacaccat tctcctgcct
    10021 cagcctccca agtagctggg actacaggtg cccgccacca tgcccggcta attttttata
    10081 tttttagtag agaaggggtt cactgtgtta gccaggatgg tcttgatctg acctcgtgat
    10141 ccgcctgcct cggcctccca aagtgctggg attacaggcg tgagccaccc cacctggcca
    10201 ttttcttttt tttttgaggt ggagttttcg cccttgctgc ccaggctgga gtgcagtggt
    10261 acgatctcag ctcactgcaa cctccacctc ctgggttcaa gcgattctcc tgcctcagcc
    10321 tcccaaatag ctgggattac aggtgcctgc caccaccact ggttaatttt tgtattttta
    10381 gtagatacgg ggtttcacca tgtcagccag gctggtctca aacttctgac ctcagatatc
    10441 cacctgcctc agcctcctaa aatggtggca ttacaggcgt gagccaccgc tcctggccca
    10501 tcatttccat atctatgaaa tctattttgg attttagagt ggatttaaat tttcaatatt
    10561 tcagtgacct cattgttaaa gctgctttgc cacttgtaca agtttgaaaa ccattgttga
    10621 atcatatgga gctttactct aattccaaat agttaaagga tgaatcaggt taaataatgc
    10681 tgttggataa tacaggcaaa aacaggattt aaacccgcac attaaaagca tgactgaagg
    10741 cccggcaggt ggatcacttt ggcccaggag ttcaaaactg acctgaacaa tgtggcgaaa
    10801 tcctgtctct actaaaaata caaaaaccag ccaggcatgt tggcgcatac ttgtaatctc
    10861 agctactcag gaggctgaga catgagaatt gcttgaacct tttaggcgga ggttgcagtg
    10921 agccgagatc atgccattgc gcgacagagc aagtctctgt ctcgcaaaaa aaaaaaaaaa
    10981 gtttaattct aacattgccc atggattttt ttttttctgt acagcttgaa gataagatag
    11041 ttaaagactc tgttacaatt taaacatcat aaaaatgtga agagtaagtg gtgaggcaag
    11101 aaacaaaatt gggggaaatg gtggggatcg tgaatatata agtgaagttt tattttttta
    11161 aggtgtaaag gagtgagaat agagtaattg ctttttaaaa agaaagtata aatgggttaa
    11221 tttttttctt ccaactttga ctttaattca gtaagaaagg cctaggtttc atctcatatt
    11281 cttcataatt gattttcaag aagttaattt gtcattcagc ctaggaggct ataaaacagc
    11341 agttagttgg cattattaga ctaaaacttg ggtgggggga ggagactgtt tcctcattgc
    11401 tgcaacccat ggtctatcct attcctaagc cattagaaag accttgtact ttgtatagaa
    11461 acattagagt gaggttttga tttttaacat agtactctca aactttgatg tgcatatgaa
    11521 caagtggatt ctgattcagt agatctgcat tgggccccgt gagtcttttt aaacacagtc
    11581 ccaggtgatt catgcagatg cctgtgaact gcgctggtag atgggcctaa gaggcttcag
    11641 gctgtgtttt aggttttggt aagccaggca gattcaagtc cttttataac tgtcaatttt
    11701 gtgaattggg gatgcagact ggttttgaag gcttaaagtt caaaaattat aagaaagtta
    11761 agaattttgc ttaagagcct tttaaaaata tggacgattt attttttaag taggcagact
    11821 aagaatttca agttataaag aatcttattg ataaggcaaa gtagacaaag tattttctca
    11881 tgagtatttg tgggttatgt ttttgttaat ataaaagttg atttctaagt attagaatat
    11941 atttagtctc taaataaatc ttgccttcta ttatggatca tcgttattaa taaacatgga
    12001 aaatcaacac tacccctaat attaatctgg cagttaaatt tagtagtgct ataatgaata
    12061 agtcagtcta gcagatatgc cctgtcatta tactgcggac ctctggtcac ttaattttct
    12121 gttatattat gtggttgaaa attcctgttt catcgtaaag tgaaatttga aagatggagt
    12181 tgaataatat gattctcgaa aagtgagttt ttcttggaat tctgttaagg tgttagattt
    12241 tcctcacata tttaaataat ctgtaagaac taccctgaaa gcactaagga aaatgtagcc
    12301 gaaagttaag taataggttt taaaaattta tcaaaattta ttgatagttt gatctgtaaa
    12361 acaaattggg tttcgtgctt tctgatgtcc agttaataag tatattatgt gccaggcttt
    12421 acatattgct ctttgcaagt agccgttaaa gtgtaagtca ttgaagtttg aagatctata
    12481 aatatttaat atagtagtct aaacagttgt gagaatttac tcagttctga aatagaatgt
    12541 taaattttcc gatgtggtcc taatcatttt tttctttaca tactaagcct tcctttctcc
    12601 aaagaacagt taaaaccaaa tgtgttatgg taagctgtaa ataccgttgg aataaaagat
    12661 aaccgttcat cttacctaaa aaattgaaga caatattttc cattgttgat gtcacaagta
    12721 agaaaaaaac tctaactttt gtactctact tgtagcagag ggaatatttt tggccacagt
    12781 gtgccaattt ataattgtag ataaagctga atttactggg cagcaagctt atatgctgat
    12841 agaagttgat gcactgagaa gtgatgagtt gaagagaatg gaaaaggcag attgagctgg
    12901 aattttaatg catagtacat ttagtagaga gacaagctgt cctatatact cctgtatact
    12961 tcagaaatag ctgatagcct atagtctctg agagctattc tgtacatagc acagtattat
    13021 aattgatgtt cataaatacc ctgagagatt atgttaaaat acattattaa tactcccaca
    13081 aaagcagtaa gttaataagt atttccaaca aaaggcagct ttgtttctta aacggataaa
    13141 caacatataa ctaggaagat catcttcaaa ataaagtgtc atggaactga aaatagagta
    13201 tagtctaaca attattttga tacactattg aatagctaac aagtgtctaa agaatttttt
    13261 atttttatag aataggaagt ttctaaaaga aaacaattaa gagcaaaatt ggttttgagt
    13321 atagaaactg aaggatggca gtcttaactc ctaagttttt tacagagcac agattggtaa
    13381 actagcatgc cacctgtttt ttgtactatc tgtgagctga gactggtttt tacatttttt
    13441 aatggtgaaa aaagtcaaaa gaaggacatt ttgtgacaca tgaaaacata ttaaattaaa
    13501 atttcagtat ccagaaataa agttttattg gaacagctgt gcttattgtc tttagctgct
    13561 ttcctggtac agtggctgag tttagtagta tagcagagtc tgtatggctt ccaacagtca
    13621 aaatactgcc tggcctttta aagagtttgt caatcccttt tatggaggaa ggttttgctc
    13681 atgcatggca tgttagtcaa tttagttatt tgcttctagc tggcagaatg tggtcttgat
    13741 tacttaattt ctgttacccc tgtgttttcc agaatggctt ctcctgattt tacttacgtg
    13801 ttttactatt gctcaaatta cagatactag gaaacactac tactttataa gtacacttct
    13861 ttttcctact taaactctca aactacagtt acgtatttgc catgatgtta agggaccttg
    13921 atggtctgtg aattatcagt tgctttctgc actacctcct gtagatagac ctgactgata
    13981 gcacttacaa aaagactgat agatgccaaa tcagtcattt attaaccctc taatattgtt
    14041 gtcccgatca tttggtaaac gctaagagag cttagtttta cattcacaaa gtatttgtat
    14101 ttgataagtc ttaaaaatga tttaagttga agcctaacag aagtacttgt tcattcctca
    14161 gttacctgca aataatggaa ataatggtgc agtcagtttt atttgattgt gtaatgcttt
    14221 atactagggg tctcaaaccc ctgggtggca ttagattctt acaggagcgt gaaccctatt
    14281 gtgaactgca catgcaagag atctaggttg tgcgctcatt atgagaatct aatacccgat
    14341 gatctgaggt ggaacagtct catcctgaaa ccatctaccc caacacctgt gtctgtggaa
    14401 attgtctcca cgaaaccggt ccctgttgaa aaaaggttag gggaccactg ctttatacag
    14461 tgtttgaagt aggcacactt acagttacta tttctggttc tttatgactg ttgagggggg
    14521 gcagaattct atgtttgatt cacagtaaaa cttttcatga atcattgagg gttaactgtt
    14581 atcacttgcc aatggaaact ggatattgaa acattttttt aagaaatgca cttttacctg
    14641 aaataaaact ataaaaacta aa
//
