LOCUS       NM_000553               7575 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens WRN RecQ like helicase (WRN), mRNA.
ACCESSION   NM_000553
VERSION     NM_000553.6
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 7575)
  AUTHORS   Silva,J.P.L., Donaires,F.S., Gutierrez-Rodrigues,F., Martins,D.J.,
            Carvalho,V.S., Santana,B.A., Cunha,R.L.G., Kajigaya,S.,
            Menck,C.F.M., Young,N.S., Kjeldsen,E. and Calado,R.T.
  TITLE     RecQ helicase expression in patients with telomeropathies
  JOURNAL   Mol Biol Rep 51 (1), 754 (2024)
   PUBMED   38874681
  REMARK    GeneRIF: RecQ helicase expression in patients with telomeropathies.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 7575)
  AUTHORS   Yoon,J.H., Sellamuthu,K., Prakash,L. and Prakash,S.
  TITLE     WRN exonuclease imparts high fidelity on translesion synthesis by Y
            family DNA polymerases
  JOURNAL   Genes Dev 38 (5-6), 213-232 (2024)
   PUBMED   38503516
  REMARK    GeneRIF: WRN exonuclease imparts high fidelity on translesion
            synthesis by Y family DNA polymerases.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 7575)
  AUTHORS   Zong,D., Koussa,N.C., Cornwell,J.A., Pankajam,A.V., Kruhlak,M.J.,
            Wong,N., Chari,R., Cappell,S.D. and Nussenzweig,A.
  TITLE     Comprehensive mapping of cell fates in microsatellite unstable
            cancer cells supports dual targeting of WRN and ATR
  JOURNAL   Genes Dev 37 (19-20), 913-928 (2023)
   PUBMED   37932011
  REMARK    GeneRIF: Comprehensive mapping of cell fates in microsatellite
            unstable cancer cells supports dual targeting of WRN and ATR.
REFERENCE   4  (bases 1 to 7575)
  AUTHORS   Shin,S., Hyun,K., Lee,J., Joo,D., Kulikowicz,T., Bohr,V.A., Kim,J.
            and Hohng,S.
  TITLE     Werner syndrome protein works as a dimer for unwinding and
            replication fork regression
  JOURNAL   Nucleic Acids Res 51 (1), 337-348 (2023)
   PUBMED   36583333
  REMARK    GeneRIF: Werner syndrome protein works as a dimer for unwinding and
            replication fork regression.
REFERENCE   5  (bases 1 to 7575)
  AUTHORS   Sezer,A., Kayhan,G., Gursoy,T.R., Eyuboglu,T.S. and Percin,F.E.
  TITLE     A homozygous missense variant in the WRN gene segregating in a
            family with progressive pulmonary failure with recurrent
            spontaneous pneumothorax and interstitial lung disease
  JOURNAL   Am J Med Genet A 191 (1), 220-227 (2023)
   PUBMED   36214313
  REMARK    GeneRIF: A homozygous missense variant in the WRN gene segregating
            in a family with progressive pulmonary failure with recurrent
            spontaneous pneumothorax and interstitial lung disease.
REFERENCE   6  (bases 1 to 7575)
  AUTHORS   Matsumoto,T., Imamura,O., Yamabe,Y., Kuromitsu,J., Tokutake,Y.,
            Shimamoto,A., Suzuki,N., Satoh,M., Kitao,S., Ichikawa,K.,
            Kataoka,H., Sugawara,K., Thomas,W., Mason,B., Tsuchihashi,Z.,
            Drayna,D., Sugawara,M., Sugimoto,M., Furuichi,Y. and Goto,M.
  TITLE     Mutation and haplotype analyses of the Werner's syndrome gene based
            on its genomic structure: genetic epidemiology in the Japanese
            population
  JOURNAL   Hum Genet 100 (1), 123-130 (1997)
   PUBMED   9225981
REFERENCE   7  (bases 1 to 7575)
  AUTHORS   Ye,L., Miki,T., Nakura,J., Oshima,J., Kamino,K., Rakugi,H.,
            Ikegami,H., Higaki,J., Edland,S.D., Martin,G.M. and Ogihara,T.
  TITLE     Association of a polymorphic variant of the Werner helicase gene
            with myocardial infarction in a Japanese population
  JOURNAL   Am J Med Genet 68 (4), 494-498 (1997)
   PUBMED   9021029
  REMARK    Erratum:[Am J Med Genet 1997 May 2;70(1):103]
REFERENCE   8  (bases 1 to 7575)
  AUTHORS   Yu,C.E., Oshima,J., Fu,Y.H., Wijsman,E.M., Hisama,F., Alisch,R.,
            Matthews,S., Nakura,J., Miki,T., Ouais,S., Martin,G.M., Mulligan,J.
            and Schellenberg,G.D.
  TITLE     Positional cloning of the Werner's syndrome gene
  JOURNAL   Science 272 (5259), 258-262 (1996)
   PUBMED   8602509
REFERENCE   9  (bases 1 to 7575)
  AUTHORS   Oshima,J., Martin,G.M. and Hisama,F.M.
  TITLE     Werner Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301687
REFERENCE   10 (bases 1 to 7575)
  AUTHORS   Goto,M., Rubenstein,M., Weber,J., Woods,K. and Drayna,D.
  TITLE     Genetic linkage of Werner's syndrome to five markers on chromosome
            8
  JOURNAL   Nature 355 (6362), 735-738 (1992)
   PUBMED   1741060
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC084736.5 and AC009563.12.
            
            On Jul 25, 2019 this sequence version replaced NM_000553.5.
            
            Summary: This gene encodes a member of the RecQ subfamily of DNA
            helicase proteins. The encoded nuclear protein is important in the
            maintenance of genome stability and plays a role in DNA repair,
            replication, transcription and telomere maintenance. This protein
            contains a N-terminal 3' to 5' exonuclease domain, an ATP-dependent
            helicase domain and RQC (RecQ helicase conserved region) domain in
            its central region, and a C-terminal HRDC (helicase RNase D
            C-terminal) domain and nuclear localization signal. Defects in this
            gene are the cause of Werner syndrome, an autosomal recessive
            disorder characterized by accelerated aging and an elevated risk
            for certain cancers. [provided by RefSeq, Aug 2017].
            
            Sequence Note: The RefSeq transcript and protein were derived from
            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 :: SRR14038197.890559.1, AF091214.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000298139.7/ ENSP00000298139.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-164               AC084736.5         65164-65327
            165-336             AC084736.5         89726-89897
            337-449             AC084736.5         90507-90619
            450-595             AC084736.5         95643-95788
            596-744             AC084736.5         96269-96417
            745-894             AC084736.5         98387-98536
            895-964             AC084736.5         99612-99681
            965-1079            AC084736.5         107527-107641
            1080-1509           AC084736.5         112221-112650
            1510-1590           AC084736.5         115053-115133
            1591-1671           AC084736.5         116520-116600
            1672-1816           AC084736.5         119130-119274
            1817-1892           AC084736.5         120244-120319
            1893-1960           AC084736.5         121819-121886
            1961-2069           AC084736.5         122188-122296
            2070-2138           AC084736.5         123184-123252
            2139-2221           AC084736.5         128122-128204
            2222-2328           AC084736.5         132203-132309
            2329-2513           AC084736.5         142969-143153
            2514-2688           AC084736.5         147708-147882
            2689-2870           AC084736.5         151597-151778
            2871-2972           AC084736.5         155876-155977
            2973-3065           AC084736.5         156262-156354
            3066-3207           AC084736.5         163719-163860
            3208-3378           AC084736.5         172784-172954
            3379-3473           AC084736.5         173035-173129
            3474-3549           AC084736.5         173980-174055
            3550-3623           AC084736.5         174904-174977
            3624-3699           AC084736.5         178407-178482
            3700-3812           AC084736.5         178718-178830
            3813-3927           AC009563.12        115544-115658       c
            3928-4059           AC009563.12        111244-111375       c
            4060-4222           AC009563.12        108469-108631       c
            4223-4431           AC009563.12        98769-98977         c
            4432-7575           AC009563.12        89861-93004         c
FEATURES             Location/Qualifiers
     source          1..7575
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8p12"
     gene            1..7575
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /note="WRN RecQ like helicase"
                     /db_xref="GeneID:7486"
                     /db_xref="HGNC:HGNC:12791"
                     /db_xref="MIM:604611"
     exon            1..164
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            165..336
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     CDS             241..4539
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /EC_number="5.6.2.4"
                     /note="Werner syndrome ATP-dependent helicase; Werner
                     syndrome protein; Werner syndrome, RecQ helicase-like;
                     exonuclease WRN; recQ protein-like 2; DNA helicase,
                     RecQ-like type 3; Werner syndrome RecQ like helicase"
                     /codon_start=1
                     /product="bifunctional 3'-5' exonuclease/ATP-dependent
                     helicase WRN"
                     /protein_id="NP_000544.2"
                     /db_xref="CCDS:CCDS6082.1"
                     /db_xref="GeneID:7486"
                     /db_xref="HGNC:HGNC:12791"
                     /db_xref="MIM:604611"
                     /translation="MSEKKLETTAQQRKCPEWMNVQNKRCAVEERKACVRKSVFEDDL
                     PFLEFTGSIVYSYDASDCSFLSEDISMSLSDGDVVGFDMEWPPLYNRGKLGKVALIQL
                     CVSESKCYLFHVSSMSVFPQGLKMLLENKAVKKAGVGIEGDQWKLLRDFDIKLKNFVE
                     LTDVANKKLKCTETWSLNSLVKHLLGKQLLKDKSIRCSNWSKFPLTEDQKLYAATDAY
                     AGFIIYRNLEILDDTVQRFAINKEEEILLSDMNKQLTSISEEVMDLAKHLPHAFSKLE
                     NPRRVSILLKDISENLYSLRRMIIGSTNIETELRPSNNLNLLSFEDSTTGGVQQKQIR
                     EHEVLIHVEDETWDPTLDHLAKHDGEDVLGNKVERKEDGFEDGVEDNKLKENMERACL
                     MSLDITEHELQILEQQSQEEYLSDIAYKSTEHLSPNDNENDTSYVIESDEDLEMEMLK
                     HLSPNDNENDTSYVIESDEDLEMEMLKSLENLNSGTVEPTHSKCLKMERNLGLPTKEE
                     EEDDENEANEGEEDDDKDFLWPAPNEEQVTCLKMYFGHSSFKPVQWKVIHSVLEERRD
                     NVAVMATGYGKSLCFQYPPVYVGKIGLVISPLISLMEDQVLQLKMSNIPACFLGSAQS
                     ENVLTDIKLGKYRIVYVTPEYCSGNMGLLQQLEADIGITLIAVDEAHCISEWGHDFRD
                     SFRKLGSLKTALPMVPIVALTATASSSIREDIVRCLNLRNPQITCTGFDRPNLYLEVR
                     RKTGNILQDLQPFLVKTSSHWEFEGPTIIYCPSRKMTQQVTGELRKLNLSCGTYHAGM
                     SFSTRKDIHHRFVRDEIQCVIATIAFGMGINKADIRQVIHYGAPKDMESYYQEIGRAG
                     RDGLQSSCHVLWAPADINLNRHLLTEIRNEKFRLYKLKMMAKMEKYLHSSRCRRQIIL
                     SHFEDKQVQKASLGIMGTEKCCDNCRSRLDHCYSMDDSEDTSWDFGPQAFKLLSAVDI
                     LGEKFGIGLPILFLRGSNSQRLADQYRRHSLFGTGKDQTESWWKAFSRQLITEGFLVE
                     VSRYNKFMKICALTKKGRNWLHKANTESQSLILQANEELCPKKLLLPSSKTVSSGTKE
                     HCYNQVPVELSTEKKSNLEKLYSYKPCDKISSGSNISKKSIMVQSPEKAYSSSQPVIS
                     AQEQETQIVLYGKLVEARQKHANKMDVPPAILATNKILVDMAKMRPTTVENVKRIDGV
                     SEGKAAMLAPLLEVIKHFCQTNSVQTDLFSSTKPQEEQKTSLVAKNKICTLSQSMAIT
                     YSLFQEKKMPLKSIAESRILPLMTIGMHLSQAVKAGCPLDLERAGLTPEVQKIIADVI
                     RNPPVNSDMSKISLIRMLVPENIDTYLIHMAIEILKHGPDSGLQPSCDVNKRRCFPGS
                     EEICSSSKRSKEEVGINTETSSAERKRRLPVWFAKGSDTSKKLMDKTKRGGLFS"
     exon            337..449
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            450..595
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            596..744
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            745..894
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            895..964
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            965..1079
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            1080..1509
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            1510..1590
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            1591..1671
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            1672..1816
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            1817..1892
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            1893..1960
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            1961..2069
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            2070..2138
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            2139..2221
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            2222..2328
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            2329..2513
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            2514..2688
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            2689..2870
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            2871..2972
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            2973..3065
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            3066..3207
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            3208..3378
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            3379..3473
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            3474..3549
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            3550..3623
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            3624..3699
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            3700..3812
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            3813..3927
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            3928..4059
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            4060..4222
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            4223..4431
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     exon            4432..7575
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5168..5173
                     /regulatory_class="polyA_signal_sequence"
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /note="hexamer: AATAAA"
     polyA_site      5193
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /note="major polyA site"
     regulatory      7335..7340
                     /regulatory_class="polyA_signal_sequence"
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /note="hexamer: AACAAG"
     polyA_site      7353
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
     regulatory      7544..7549
                     /regulatory_class="polyA_signal_sequence"
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
                     /note="hexamer: ATTAAA"
     polyA_site      7575
                     /gene="WRN"
                     /gene_synonym="RECQ3; RECQL2; RECQL3"
ORIGIN      
        1 gtgtactgtg tgcgccgggg aggcgccggc ttgtactcgg cagcgcggga ataaagtttg
       61 ctgatttggt gtctagcctg gatgcctggg ttgcaggccc tgcttgtggt ggcgctccac
      121 agtcatccgg ctgaagaaga cctgttggac tggatcttct cgggttttct ttcagatatt
      181 gttttgtatt tacccatgaa gacattgttt tttggactct gcaaatagga catttcaaag
      241 atgagtgaaa aaaaattgga aacaactgca cagcagcgga aatgtcctga atggatgaat
      301 gtgcagaata aaagatgtgc tgtagaagaa agaaaggcat gtgttcggaa gagtgttttt
      361 gaagatgacc tccccttctt agaattcact ggatccattg tgtatagtta cgatgctagt
      421 gattgctctt tcctgtcaga agatattagc atgagtctat cagatgggga tgtggtggga
      481 tttgacatgg agtggccacc attatacaat agagggaaac ttggcaaagt tgcactaatt
      541 cagttgtgtg tttctgagag caaatgttac ttgttccacg tttcttccat gtcagttttt
      601 ccccagggat taaaaatgtt gcttgaaaat aaagcagtta aaaaggcagg tgtaggaatt
      661 gaaggagatc agtggaaact tctacgtgac tttgatatca aattgaagaa ttttgtggag
      721 ttgacagatg ttgccaataa aaagctgaaa tgcacagaga cctggagcct taacagtctg
      781 gttaaacacc tcttaggtaa acagctcctg aaagacaagt ctatccgctg tagcaattgg
      841 agtaaatttc ctctcactga ggaccagaaa ctgtatgcag ccactgatgc ttatgctggt
      901 tttattattt accgaaattt agagattttg gatgatactg tgcaaaggtt tgctataaat
      961 aaagaggaag aaatcctact tagcgacatg aacaaacagt tgacttcaat ctctgaggaa
     1021 gtgatggatc tggctaagca tcttcctcat gctttcagta aattggaaaa cccacggagg
     1081 gtttctatct tactaaagga tatttcagaa aatctatatt cactgaggag gatgataatt
     1141 gggtctacta acattgagac tgaactgagg cccagcaata atttaaactt attatccttt
     1201 gaagattcaa ctactggggg agtacaacag aaacaaatta gagaacatga agttttaatt
     1261 cacgttgaag atgaaacatg ggacccaaca cttgatcatt tagctaaaca tgatggagaa
     1321 gatgtacttg gaaataaagt ggaacgaaaa gaagatggat ttgaagatgg agtagaagac
     1381 aacaaattga aagagaatat ggaaagagct tgtttgatgt cgttagatat tacagaacat
     1441 gaactccaaa ttttggaaca gcagtctcag gaagaatatc ttagtgatat tgcttataaa
     1501 tctactgagc atttatctcc caatgataat gaaaacgata cgtcctatgt aattgagagt
     1561 gatgaagatt tagaaatgga gatgcttaag catttatctc ccaatgataa tgaaaacgat
     1621 acgtcctatg taattgagag tgatgaagat ttagaaatgg agatgcttaa gtctttagaa
     1681 aacctcaata gtggcacggt agaaccaact cattctaaat gcttaaaaat ggaaagaaat
     1741 ctgggtcttc ctactaaaga agaagaagaa gatgatgaaa atgaagctaa tgaaggggaa
     1801 gaagatgatg ataaggactt tttgtggcca gcacccaatg aagagcaagt tacttgcctc
     1861 aagatgtact ttggccattc cagttttaaa ccagttcagt ggaaagtgat tcattcagta
     1921 ttagaagaaa gaagagataa tgttgctgtc atggcaactg gatatggaaa gagtttgtgc
     1981 ttccagtatc cacctgttta tgtaggcaag attggccttg ttatctctcc ccttatttct
     2041 ctgatggaag accaagtgct acagcttaaa atgtccaaca tcccagcttg cttccttgga
     2101 tcagcacagt cagaaaatgt tctaacagat attaaattag gtaaataccg gattgtatac
     2161 gtaactccag aatactgttc aggtaacatg ggcctgctcc agcaacttga ggctgatatt
     2221 ggtatcacgc tcattgctgt ggatgaggct cactgtattt ctgagtgggg gcatgatttt
     2281 agggattcat tcaggaagtt gggctcccta aagacagcac tgccaatggt tccaatcgtt
     2341 gcacttactg ctactgcaag ttcttcaatc cgggaagaca ttgtacgttg cttaaatctg
     2401 agaaatcctc agatcacctg tactggtttt gatcgaccaa acctgtattt agaagttagg
     2461 cgaaaaacag ggaatatcct tcaggatctg cagccatttc ttgtcaaaac aagttcccac
     2521 tgggaatttg aaggtccaac aatcatctac tgtccttcta gaaaaatgac acaacaagtt
     2581 acaggtgaac ttaggaaact gaatctatcc tgtggaacat accatgcggg catgagtttt
     2641 agcacaagga aagacattca tcataggttt gtaagagatg aaattcagtg tgtcatagct
     2701 accatagctt ttggaatggg cattaataaa gctgacattc gccaagtcat tcattacggt
     2761 gctcctaagg acatggaatc atattatcag gagattggta gagctggtcg tgatggactt
     2821 caaagttctt gtcacgtcct ctgggctcct gcagacatta acttaaatag gcaccttctt
     2881 actgagatac gtaatgagaa gtttcgatta tacaaattaa agatgatggc aaagatggaa
     2941 aaatatcttc attctagcag atgtaggaga caaatcatct tgtctcattt tgaggacaaa
     3001 caagtacaaa aagcctcctt gggaattatg ggaactgaaa aatgctgtga taattgcagg
     3061 tccagattgg atcattgcta ttccatggat gactcagagg atacatcctg ggactttggt
     3121 ccacaagcat ttaagctttt gtctgctgtg gacatcttag gcgaaaaatt tggaattggg
     3181 cttccaattt tatttctccg aggatctaat tctcagcgtc ttgccgatca atatcgcagg
     3241 cacagtttat ttggcactgg caaggatcaa acagagagtt ggtggaaggc tttttcccgt
     3301 cagctgatca ctgagggatt cttggtagaa gtttctcggt ataacaaatt tatgaagatt
     3361 tgcgccctta cgaaaaaggg tagaaattgg cttcataaag ctaatacaga atctcagagc
     3421 ctcatccttc aagctaatga agaattgtgt ccaaagaagt tgcttctgcc tagttcgaaa
     3481 actgtatctt cgggcaccaa agagcattgt tataatcaag taccagttga attaagtaca
     3541 gagaagaagt ctaacttgga gaagttatat tcttataaac catgtgataa gatttcttct
     3601 gggagtaaca tttctaaaaa aagtatcatg gtacagtcac cagaaaaagc ttacagttcc
     3661 tcacagcctg ttatttcggc acaagagcag gagactcaga ttgtgttata tggcaaattg
     3721 gtagaagcta ggcagaaaca tgccaataaa atggatgttc ccccagctat tctggcaaca
     3781 aacaagatac tggtggatat ggccaaaatg agaccaacta cggttgaaaa cgtaaaaagg
     3841 attgatggtg tttctgaagg caaagctgcc atgttggccc ctctgttgga agtcatcaaa
     3901 catttctgcc aaacaaatag tgttcagaca gacctctttt caagtacaaa acctcaagaa
     3961 gaacagaaga cgagtctggt agcaaaaaat aaaatatgca cactttcaca gtctatggcc
     4021 atcacatact ctttattcca agaaaagaag atgcctttga agagcatagc tgagagcagg
     4081 attctgcctc tcatgacaat tggcatgcac ttatcccaag cggtgaaagc tggctgcccc
     4141 cttgatttgg agcgagcagg cctgactcca gaggttcaga agattattgc tgatgttatc
     4201 cgaaaccctc ccgtcaactc agatatgagt aaaattagcc taatcagaat gttagttcct
     4261 gaaaacattg acacgtacct tatccacatg gcaattgaga tccttaaaca tggtcctgac
     4321 agcggacttc aaccttcatg tgatgtcaac aaaaggagat gttttcccgg ttctgaagag
     4381 atctgttcaa gttctaagag aagcaaggaa gaagtaggca tcaatactga gacttcatct
     4441 gcagagagaa agagacgatt acctgtgtgg tttgccaaag gaagtgatac cagcaagaaa
     4501 ttaatggaca aaacgaaaag gggaggtctt tttagttaag ctggcaatta ccagaacaat
     4561 tatgtttctt gctgtattat aagaggatag ctatatttta tttctgaaga gtaaggagta
     4621 gtattttggc ttaaaaatca ttctaattac aaagttcact gtttattgaa gaactggcat
     4681 cttaaatcag ccttccgcaa ttcatgtagt ttctgggtct tctgggagcc tacgtgagta
     4741 catcacctaa cagaatatta aattagactt cctgtaagat tgctttaaga aactgttact
     4801 gtcctgtttt ctaatctctt tattaaaaca gtgtatttgg aaaatgttat gtgctctgat
     4861 ttgatataga taacagatta gtagttacat ggtaattatg tgatataaaa tattcatata
     4921 ttatcaaaat tctgttttgt aaatgtaaga aagcatagtt attttacaaa ttgtttttac
     4981 tgtcttttga agaagttctt aaatacgttg ttaaatggta ttagttgacc agggcagtga
     5041 aaatgaaacc gcattttggg tgccattaaa tagggaaaaa acatgtaaaa aatgtaaaat
     5101 ggagaccaat tgcactaggc aagtgtatat tttgtatttt atatacaatt tctattattt
     5161 ttcaagtaat aaaacaatgt ttttcatact gaatattata tatatatttt ttagctttca
     5221 tttacttaat tattttaagt acctttattt ttccaggatg tcagaatttg attctaatct
     5281 ctcttatgta gcacatgtga cttaatttaa aacctatact gtgacacaga gttgggtaaa
     5341 cgatgattat ttaactttaa gcagttcacc atccatttca aagcctttga ttggcttttt
     5401 tgtaaataaa aataacttgt taagaaacaa atatatctgt catagaagaa ctagaaaatc
     5461 cagggaagtg agaaaaatga aaataaaaat cattcatagt tttactagta gctaatcaca
     5521 gtcaacctct tttgtgtatc ccaccagact tttttatatt catttgtttt tagttaaaat
     5581 ataaaagtct cgtatattcc catttttctg cattgcatta ccagaaggta gtggcgccta
     5641 ttaaatatgt gatatgttgt tgtccagcca tggcttctgc atttgcatgc ttttgtgtgt
     5701 gcatctgcaa taccctgtga atatcctgtg tgatggagtg gcaagtacgc acagacacgt
     5761 ctgctgcatg cctaggtacg aggctgtctc caggagaagc acttgtttga ttatttgagt
     5821 tgccaattga atttgctgct ttttttcatg gcttgccatt ttcactgaaa agaatgacta
     5881 atgaaaaacg atgattggtt attagatttg gatgtttggc agacattttc tcaaaattga
     5941 actaagttgg cctcttcacg gaaaacaact ggtatttgtt gtgccaatga taaaattgga
     6001 gatttctagc aaaatgtata attttggaaa agttgtgttc ctccactgga agcttgacag
     6061 ctttccttaa cataaagact tctctttctc ttcgctttca ctactactac tactaattct
     6121 tcttctgatt cttcttcttc tccttcttcc ttcttccttc cttcctcctc ctcctccttc
     6181 ttcttcctct tcctcttctt ctttctctct ttccttcctt cccttccctt ccccttcctt
     6241 ccttccttcc ttccttcctc cctccctccc tccctccctc cctccctcct ttctttttct
     6301 ttctctttct ttctttcttt ctctctctct ctctctttct ttctttttct ttctcttttt
     6361 ctttctttca agcagtcctc ccgcctcagt cccccaaaat agtgggatta caggtgtgag
     6421 ccaccatgca cagccttaca taaagccttt tctaatgaga tggatagtaa ttaacaaatg
     6481 tgagtttttg atattatata aagatttttt ctgtgtttcg aagatccgta taactcagtg
     6541 aatcagtatg ttctggatga ctaatatgtg atgttaagaa atcatgactg aggccgggcg
     6601 cggtggctca cgcctgtaat cccagcactt tgggaggccg aggcgggcgg atcacgagat
     6661 caggagatcg agaccaccct ggccaacatg gtgaaacccc gtctctacta aaaatacaaa
     6721 aattagctgg gtgtgttggt gcgtgcctat aatcccagct actcgggagg ctgaggcagg
     6781 agaatcgctt gaactcagga ggcggagatt gcagtgagct gagactgcgc cactgcaccc
     6841 cagcctggcg acagagcaag actccgtctc aaaaataaaa aaagaaatca tgactgggta
     6901 aaagatctgt tcagagtaca agatggacca atggatttga tatatttgaa tataacagag
     6961 tatgaaaaag tttattgata tagtttcaga ttacacactg caactaatct ttaagaaact
     7021 attacttgtc cactttttgg taaaatttca gagaacaatg tccaccatta tctgaacagg
     7081 ctattaaaat actcttctct tttccaacta cgtgcctgtg caaagtcaga tttttttcat
     7141 atacttcagc caaaacagca tatcaaaatg gattgaatgc agaagtagat ctgagaatac
     7201 agccactttt gttaagccag acaatgagat ttgcaaaatg taaacaatgc tgctgttctc
     7261 agtttttaaa aatatgtttt ttaaaagtat ttatgttaat gtgtacttgg tttactactg
     7321 ctatttttaa ataaaacaag aaacattttt aaatgtctgt tttaatttct aaagtggtag
     7381 tgatagatat aacccatatt aataaaagct ctttggggtc ctcagtgatt tttttttaag
     7441 agtatggaag ggttctcaga cctaagagat tgagaaatgc tgatgtaatg ttttattata
     7501 aaggtgtacc atgaattatg taccttactt catattgttg gacattaaag ttgctttcag
     7561 tttttttgtt ttaaa
//
