LOCUS       NM_013372              14575 bp    mRNA    linear   PRI 24-SEP-2024
DEFINITION  Homo sapiens gremlin 1, DAN family BMP antagonist (GREM1),
            transcript variant 1, mRNA.
ACCESSION   NM_013372
VERSION     NM_013372.7
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 14575)
  AUTHORS   Diao,S., Han,X., Ye,W.L., Zhang,C., Yang,D.M., Fan,Z.P. and
            Wang,S.L.
  TITLE     GREM1 Negatively Regulates Osteo-/Dentinogenic Differentiation of
            Dental Pulp Stem Cells via Association with YWHAH
  JOURNAL   Chin J Dent Res 27 (3), 203-213 (2024)
   PUBMED   39221981
  REMARK    GeneRIF: GREM1 Negatively Regulates Osteo-/Dentinogenic
            Differentiation of Dental Pulp Stem Cells via Association with
            YWHAH.
REFERENCE   2  (bases 1 to 14575)
  AUTHORS   Kupryte,M., Lesauskaite,V., Sirataviciute,V., Utkiene,L.,
            Jusiene,L. and Pangonyte,D.
  TITLE     Expression of Osteopontin and Gremlin 1 Proteins in Cardiomyocytes
            in Ischemic Heart Failure
  JOURNAL   Int J Mol Sci 25 (15), 8240 (2024)
   PUBMED   39125809
  REMARK    GeneRIF: Expression of Osteopontin and Gremlin 1 Proteins in
            Cardiomyocytes in Ischemic Heart Failure.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 14575)
  AUTHORS   Deng,J., Martin,S., Searl,T., Ohlander,S., Harrington,D.A.,
            McVary,K.T. and Podlasek,C.A.
  TITLE     SHH regulates penile morphology and smooth muscle through a
            mechanism involving BMP4 and GREM1
  JOURNAL   J Sex Med 21 (5), 379-390 (2024)
   PUBMED   38451321
  REMARK    GeneRIF: SHH regulates penile morphology and smooth muscle through
            a mechanism involving BMP4 and GREM1.
REFERENCE   4  (bases 1 to 14575)
  AUTHORS   Deng,J., Searl,T., Ohlander,S., Dynda,D., Harrington,D.A.,
            McVary,K.T. and Podlasek,C.A.
  TITLE     BMP4 and GREM1 are targets of SHH signaling and downstream
            regulators of collagen in the penis
  JOURNAL   J Sex Med 21 (5), 367-378 (2024)
   PUBMED   38451311
  REMARK    GeneRIF: BMP4 and GREM1 are targets of SHH signaling and downstream
            regulators of collagen in the penis.
REFERENCE   5  (bases 1 to 14575)
  AUTHORS   Faizal,A.M., Elias,M.H., Jin,N.M., Abu,M.A., Syafruddin,S.E.,
            Zainuddin,A.A., Suzuki,N. and Karim,A.K.A.
  TITLE     Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in
            cumulus cells: implications for human oocyte development competency
            - a systematic review and integrated bioinformatic analysis
  JOURNAL   Front Endocrinol (Lausanne) 15, 1274376 (2024)
   PUBMED   38524634
  REMARK    GeneRIF: Unravelling the role of HAS2, GREM1, and PTGS2 gene
            expression in cumulus cells: implications for human oocyte
            development competency - a systematic review and integrated
            bioinformatic analysis.
            Review article
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 14575)
  AUTHORS   Park,W.S., Park,J.Y., Oh,R.R., Yoo,N.J., Lee,S.H., Shin,M.S.,
            Lee,H.K., Han,S., Yoon,S.K., Kim,S.Y., Choi,C., Kim,P.J., Oh,S.T.
            and Lee,J.Y.
  TITLE     A distinct tumor suppressor gene locus on chromosome 15q21.1 in
            sporadic form of colorectal cancer
  JOURNAL   Cancer Res 60 (1), 70-73 (2000)
   PUBMED   10646855
REFERENCE   7  (bases 1 to 14575)
  AUTHORS   Merino,R., Rodriguez-Leon,J., Macias,D., Ganan,Y., Economides,A.N.
            and Hurle,J.M.
  TITLE     The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and
            programmed cell death in the developing limb
  JOURNAL   Development 126 (23), 5515-5522 (1999)
   PUBMED   10556075
REFERENCE   8  (bases 1 to 14575)
  AUTHORS   Tomlinson,I., Rahman,N., Frayling,I., Mangion,J., Barfoot,R.,
            Hamoudi,R., Seal,S., Northover,J., Thomas,H.J., Neale,K.,
            Hodgson,S., Talbot,I., Houlston,R. and Stratton,M.R.
  TITLE     Inherited susceptibility to colorectal adenomas and carcinomas:
            evidence for a new predisposition gene on 15q14-q22
  JOURNAL   Gastroenterology 116 (4), 789-795 (1999)
   PUBMED   10092300
REFERENCE   9  (bases 1 to 14575)
  AUTHORS   Murphy,M., Godson,C., Cannon,S., Kato,S., Mackenzie,H.S., Martin,F.
            and Brady,H.R.
  TITLE     Suppression subtractive hybridization identifies high glucose
            levels as a stimulus for expression of connective tissue growth
            factor and other genes in human mesangial cells
  JOURNAL   J Biol Chem 274 (9), 5830-5834 (1999)
   PUBMED   10026205
REFERENCE   10 (bases 1 to 14575)
  AUTHORS   Hsu,D.R., Economides,A.N., Wang,X., Eimon,P.M. and Harland,R.M.
  TITLE     The Xenopus dorsalizing factor Gremlin identifies a novel family of
            secreted proteins that antagonize BMP activities
  JOURNAL   Mol Cell 1 (5), 673-683 (1998)
   PUBMED   9660951
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK095890.1, AC090877.4 and
            W19275.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_013372.6.
            
            Summary: This gene encodes a member of the BMP (bone morphogenic
            protein) antagonist family. Like BMPs, BMP antagonists contain
            cystine knots and typically form homo- and heterodimers. The CAN
            (cerberus and dan) subfamily of BMP antagonists, to which this gene
            belongs, is characterized by a C-terminal cystine knot with an
            eight-membered ring. The antagonistic effect of the secreted
            glycosylated protein encoded by this gene is likely due to its
            direct binding to BMP proteins. As an antagonist of BMP, this gene
            may play a role in regulating organogenesis, body patterning, and
            tissue differentiation. In mouse, this protein has been shown to
            relay the sonic hedgehog (SHH) signal from the polarizing region to
            the apical ectodermal ridge during limb bud outgrowth.
            Alternatively spliced transcript variants encoding different
            isoforms have been found for this gene. [provided by RefSeq, Jul
            2010].
            
            Transcript Variant: This variant (1) is the longest transcript and
            encodes the longest 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 :: SRR1803612.144525.1,
                                           SRR1660803.112155.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000651154.1/ ENSP00000498748.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-273               AK095890.1         1-273
            274-3804            AC090877.4         65315-68845
            3805-4138           W19275.1           13-346              c
            4139-14575          AC090877.4         69180-79616
FEATURES             Location/Qualifiers
     source          1..14575
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q13.3"
     gene            1..14575
                     /gene="GREM1"
                     /gene_synonym="C15DUPq; CKTSF1B1; CRAC1; CRCS4; DAND2;
                     DRM; DUP15q; GREMLIN; HMPS; HMPS1; IHG-2; MPSH; PIG2"
                     /note="gremlin 1, DAN family BMP antagonist"
                     /db_xref="GeneID:26585"
                     /db_xref="HGNC:HGNC:2001"
                     /db_xref="MIM:603054"
     exon            1..158
                     /gene="GREM1"
                     /gene_synonym="C15DUPq; CKTSF1B1; CRAC1; CRCS4; DAND2;
                     DRM; DUP15q; GREMLIN; HMPS; HMPS1; IHG-2; MPSH; PIG2"
                     /inference="alignment:Splign:2.1.0"
     exon            159..14575
                     /gene="GREM1"
                     /gene_synonym="C15DUPq; CKTSF1B1; CRAC1; CRCS4; DAND2;
                     DRM; DUP15q; GREMLIN; HMPS; HMPS1; IHG-2; MPSH; PIG2"
                     /inference="alignment:Splign:2.1.0"
     CDS             160..714
                     /gene="GREM1"
                     /gene_synonym="C15DUPq; CKTSF1B1; CRAC1; CRCS4; DAND2;
                     DRM; DUP15q; GREMLIN; HMPS; HMPS1; IHG-2; MPSH; PIG2"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; cysteine knot superfamily 1, BMP antagonist 1;
                     increased in high glucose-2; gremlin 1-like protein; DAN
                     domain family member 2; colorectal adenoma and carcinoma
                     1; cell proliferation-inducing gene 2 protein;
                     down-regulated in Mos-transformed cells protein; gremlin
                     1, cysteine knot superfamily, homolog; hereditary mixed
                     polyposis syndrome"
                     /codon_start=1
                     /product="gremlin-1 isoform 1 precursor"
                     /protein_id="NP_037504.1"
                     /db_xref="CCDS:CCDS10029.1"
                     /db_xref="GeneID:26585"
                     /db_xref="HGNC:HGNC:2001"
                     /db_xref="MIM:603054"
                     /translation="MSRTAYTVGALLLLLGTLLPAAEGKKKGSQGAIPPPDKAQHNDS
                     EQTQSPQQPGSRNRGRGQGRGTAMPGEEVLESSQEALHVTERKYLKRDWCKTQPLKQT
                     IHEEGCNSRTIINRFCYGQCNSFYIPRHIRKEEGSFQSCSFCKPKKFTTMMVTLNCPE
                     LQPPTKKKRVTRVKQCRCISIDLD"
     regulatory      4113..4118
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GREM1"
                     /gene_synonym="C15DUPq; CKTSF1B1; CRAC1; CRCS4; DAND2;
                     DRM; DUP15q; GREMLIN; HMPS; HMPS1; IHG-2; MPSH; PIG2"
                     /note="hexamer: AATAAA"
     polyA_site      4134
                     /gene="GREM1"
                     /gene_synonym="C15DUPq; CKTSF1B1; CRAC1; CRCS4; DAND2;
                     DRM; DUP15q; GREMLIN; HMPS; HMPS1; IHG-2; MPSH; PIG2"
                     /note="major polyA site"
     regulatory      5418..5423
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GREM1"
                     /gene_synonym="C15DUPq; CKTSF1B1; CRAC1; CRCS4; DAND2;
                     DRM; DUP15q; GREMLIN; HMPS; HMPS1; IHG-2; MPSH; PIG2"
                     /note="hexamer: AAGAAA"
     polyA_site      5441
                     /gene="GREM1"
                     /gene_synonym="C15DUPq; CKTSF1B1; CRAC1; CRCS4; DAND2;
                     DRM; DUP15q; GREMLIN; HMPS; HMPS1; IHG-2; MPSH; PIG2"
     regulatory      14555..14560
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GREM1"
                     /gene_synonym="C15DUPq; CKTSF1B1; CRAC1; CRCS4; DAND2;
                     DRM; DUP15q; GREMLIN; HMPS; HMPS1; IHG-2; MPSH; PIG2"
                     /note="hexamer: AATAAA"
     polyA_site      14575
                     /gene="GREM1"
                     /gene_synonym="C15DUPq; CKTSF1B1; CRAC1; CRCS4; DAND2;
                     DRM; DUP15q; GREMLIN; HMPS; HMPS1; IHG-2; MPSH; PIG2"
ORIGIN      
        1 actcggtgcg ccttccgcgg accgggcgac ccagtgcacg gccgccgcgt cactctcggt
       61 cccgctgacc ccgcgccgag ccccggcggc tctggccgcg gccgcactca gcgccacgcg
      121 tcgaaagcgc aggccccgag gacccgccgc actgacagta tgagccgcac agcctacacg
      181 gtgggagccc tgcttctcct cttggggacc ctgctgccgg ctgctgaagg gaaaaagaaa
      241 gggtcccaag gtgccatccc cccgccagac aaggcccagc acaatgactc agagcagact
      301 cagtcgcccc agcagcctgg ctccaggaac cgggggcggg gccaagggcg gggcactgcc
      361 atgcccgggg aggaggtgct ggagtccagc caagaggccc tgcatgtgac ggagcgcaaa
      421 tacctgaagc gagactggtg caaaacccag ccgcttaagc agaccatcca cgaggaaggc
      481 tgcaacagtc gcaccatcat caaccgcttc tgttacggcc agtgcaactc tttctacatc
      541 cccaggcaca tccggaagga ggaaggttcc tttcagtcct gctccttctg caagcccaag
      601 aaattcacta ccatgatggt cacactcaac tgccctgaac tacagccacc taccaagaag
      661 aagagagtca cacgtgtgaa gcagtgtcgt tgcatatcca tcgatttgga ttaagccaaa
      721 tccaggtgca cccagcatgt cctaggaatg cagccccagg aagtcccaga cctaaaacaa
      781 ccagattctt acttggctta aacctagagg ccagaagaac ccccagctgc ctcctggcag
      841 gagcctgctt gtgcgtagtt cgtgtgcatg agtgtggatg ggtgcctgtg ggtgttttta
      901 gacaccagag aaaacacagt ctctgctaga gagcactccc tattttgtaa acatatctgc
      961 tttaatgggg atgtaccaga aacccacctc accccggctc acatctaaag gggcggggcc
     1021 gtggtctggt tctgactttg tgtttttgtg ccctcctggg gaccagaatc tcctttcgga
     1081 atgaatgttc atggaagagg ctcctctgag ggcaagagac ctgttttagt gctgcattcg
     1141 acatggaaaa gtccttttaa cctgtgcttg catcctcctt tcctcctcct cctcacaatc
     1201 catctcttct taagttgata gtgactatgt cagtctaatc tcttgtttgc caaggttcct
     1261 aaattaattc acttaaccat gatgcaaatg tttttcattt tgtgaagacc ctccagactc
     1321 tgggagaggc tggtgtgggc aaggacaagc aggatagtgg agtgagaaag ggagggtgga
     1381 gggtgaggcc aaatcaggtc cagcaaaagt cagtagggac attgcagaag cttgaaaggc
     1441 caataccaga acacaggctg atgcttctga gaaagtcttt tcctagtatt taacagaacc
     1501 caagtgaaca gaggagaaat gagattgcca gaaagtgatt aactttggcc gttgcaatct
     1561 gctcaaacct aacaccaaac tgaaaacata aatactgacc actcctatgt tcggacccaa
     1621 gcaagttagc taaaccaaac caactcctct gctttgtccc tcaggtggaa aagagaggta
     1681 gtttagaact ctctgcatag gggtgggaat taatcaaaaa cctcagaggc tgaaattcct
     1741 aatacctttc ctttatcgtg gttatagtca gctcatttcc attccactat ttcccataat
     1801 gcttctgaga gccactaact tgattgataa agatcctgcc tctgctgagt gtacctgaca
     1861 gtagtctaag atgagagagt ttagggacta ctctgtttta gcaagagata ttttgggggt
     1921 ctttttgttt taactattgt caggagattg ggctaaagag aagacgacga gagtaaggaa
     1981 ataaagggaa ttgcctctgg ctagagagta gttaggtgtt aatacctggt agagatgtaa
     2041 gggatatgac ctccctttct ttatgtgctc actgaggatc tgaggggacc ctgttaggag
     2101 agcatagcat catgatgtat tagctgttca tctgctactg gttggatgga cataactatt
     2161 gtaactattc agtatttact ggtaggcact gtcctctgat taaacttggc ctactggcaa
     2221 tggctactta ggattgatct aagggccaaa gtgcagggtg ggtgaacttt attgtacttt
     2281 ggatttggtt aacctgtttt cttcaagcct gaggttttat atacaaactc cctgaatact
     2341 ctttttgcct tgtatcttct cagcctccta gccaagtcct atgtaatatg gaaaacaaac
     2401 actgcagact tgagattcag ttgccgatca aggctctggc attcagagaa cccttgcaac
     2461 tcgagaagct gtttttattt cgtttttgtt ttgatccagt gctctcccat ctaacaacta
     2521 aacaggagcc atttcaaggc gggagatatt ttaaacaccc aaaatgttgg gtctgatttt
     2581 caaactttta aactcactac tgatgattct cacgctaggc gaatttgtcc aaacacatag
     2641 tgtgtgtgtt ttgtatacac tgtatgaccc caccccaaat ctttgtattg tccacattct
     2701 ccaacaataa agcacagagt ggatttaatt aagcacacaa atgctaaggc agaattttga
     2761 gggtgggaga gaagaaaagg gaaagaagct gaaaatgtaa aaccacacca gggaggaaaa
     2821 atgacattca gaaccagcaa acactgaatt tctcttgttg ttttaactct gccacaagaa
     2881 tgcaatttcg ttaacggaga tgacttaagt tggcagcagt aatcttcttt taggagcttg
     2941 taccacagtc ttgcacataa gtgcagattt ggctcaagta aagagaattt cctcaacact
     3001 aacttcactg ggataatcag cagcgtaact accctaaaag catatcacta gccaaagagg
     3061 gaaatatctg ttcttcttac tgtgcctata ttaagactag tacaaatgtg gtgtgtcttc
     3121 caactttcat tgaaaatgcc atatctatac catattttat tcgagtcact gatgatgtaa
     3181 tgatatattt tttcattatt atagtagaat atttttatgg caagatattt gtggtcttga
     3241 tcatacctat taaaataatg ccaaacacca aatatgaatt ttatgatgta cactttgtgc
     3301 ttggcattaa aagaaaaaaa cacacatcct ggaagtctgt aagttgtttt ttgttactgt
     3361 aggtcttcaa agttaagagt gtaagtgaaa aatctggagg agaggataat ttccactgtg
     3421 tggaatgtga atagttaaat gaaaagttat ggttatttaa tgtaattatt acttcaaatc
     3481 ctttggtcac tgtgatttca agcatgtttt ctttttctcc tttatatgac tttctctgag
     3541 ttgggcaaag aagaagctga cacaccgtat gttgttagag tcttttatct ggtcagggga
     3601 aacaaaatct tgacccagct gaacatgtct tcctgagtca gtgcctgaat ctttattttt
     3661 taaattgaat gttccttaaa ggttaacatt tctaaagcaa tattaagaaa gactttaaat
     3721 gttattttgg aagacttacg atgcatgtat acaaacgaat agcagataat gatgactagt
     3781 tcacacataa agtcctttta aggagaaaat ctaaaatgaa aagtggataa acagaacatt
     3841 tataagtgat cagttaatgc ctaagagtga aagtagttct attgacattc ctcaagatat
     3901 ttaatatcaa ctgcattatg tattatgtct gcttaaatca tttaaaaacg gcaaagaatt
     3961 atatagacta tgaggtacct tgctgtgtag gaggatgaaa ggggagttga tagtctcata
     4021 aaactaattt ggcttcaagt ttcatgaatc tgtaactaga atttaatttt caccccaata
     4081 atgttctata tagcctttgc taaagagcaa ctaataaatt aaacctattc tttctgtgtg
     4141 tgtgagcgtg cgtttgtgtt tggtagtgtt cctagggcag aggtggagca gggatgcact
     4201 tatcatggga agggaggtag aaaagagaat tggatagcct gtgatctttg gtggaattta
     4261 ttccttttgc ctaggccttt cagaccctgc ttgatttccg taggacactt caggttgtgg
     4321 caagggagag ctggtctgca atcggaagta ccagcctctt ccctagagca caactagaaa
     4381 gaagaactat agagtgttat aagggaggcc ctgagatgga aggaccatca cacagaaatg
     4441 ataatatctt catttcaggg tgttccaggg gaaaagcagg agaaagattt ggggctcagt
     4501 agaaggaaaa gcttcctagt ggtaagagtg attggcaata ccatgaggta cctttaaaag
     4561 atagtgaact cctgtccttg gaaatattaa accacaggct agatatcatt taatagggat
     4621 gtgaagtaga gtaagtcact gcccttggtg tgcaattgtg aacttgtcaa tttctgaggt
     4681 ccctttctac ttagatatat aatacaagat ttctattagg tatgggtgct ctgatgataa
     4741 tgaaaatccc agcagctatg tatgggatgg ttacaccaga cactgtgcta aggattttct
     4801 ttgaattgtt tctcactcaa tcttcacggt agctcagtga ggtaggtacc attatcactg
     4861 ctagaaagca gtgaacttat atggtcttac tgtggcactg ggtccttaaa cattatgcaa
     4921 aactgtgagc aacttttatc ggtttgttct tttaagaaca taacacagca ctctaaaaat
     4981 agatctaact agattgttca catctagcga ttaaggccac cctgagatta tagctgcatc
     5041 atcaggaacc caagatctga agcattcagt caaagcctct tggccacctc tctttttgtc
     5101 atggccttct tggacttgga gggggagaat ggaagcaagt accaaggaga aagtgttctc
     5161 agaaaagcca cacccattag aaaaatacaa ggcctgaaag gtgtgagtgg gacttgacac
     5221 ggaagagcat ttcaagctta agaaaaaaaa aaaaaagaag aatgtgggag gatgtcagca
     5281 acaatgcttg agattccctg gtcccccaaa gagtctctcc tccataaaac taatgagaat
     5341 gtgacaaaaa tagattcaac ttcttatagc tctggaaatt aactgaagat gtatagcaat
     5401 ttgcagagca tttattcaag aaaaagacta aatctctgtg agcactgtga tattgtaact
     5461 tgcactactc tcatctcccc ctctccagct ccacaatagc tttgaaacca acagcctgca
     5521 attaccatga aaatcagcag tctggcagcc actgaaggtg acagaatgga gttggagttc
     5581 tttcaaagtc ccattcctag acaattgtca ctatttgacc tgtttggcag gccctggaag
     5641 ctccacttgc aaggctatat ttgacctgac tggaagcttc ccagggtaaa aaactttgtc
     5701 aaaacaacta gaggcaattg attctctttg tggctgcctg gggtaatgta taacagttgg
     5761 ggaaagcaat tggctaaata aaaagcctaa aaggagaagc tggaaaaaga gattttcata
     5821 gggactttga aaagctccaa agtgttattg gcaatctaga ctgccaaatg cataaatagg
     5881 actccatcca tgcccaggac tgtgcagatg ctcaggaaaa acccaagaaa gccttaagct
     5941 ctcacttcaa gctgatcttg aggctctgca caagccataa gtaaagggaa tgcagagttg
     6001 tcaattgcat ggcggagtgt tgagtgtgcc tcagcattca cacagagctc cttggcagag
     6061 actggttgaa ttattgattc caagtgtttg aggaaatccg tgtacaacta ttagatgact
     6121 actaaccaag cagagacttc agtgtccaca cacaacaaaa aatacagact ttacagaatt
     6181 agttcagaaa agtcattaaa caaagaaaca acaacaaacc ctggggaaat gacagtacga
     6241 tcaaaccatg catggccctg cctgcatgtg ggaatcctca tccaagtcat actttctaaa
     6301 catcataaaa agcccaaacc agtctccttt cctggctctc tcaagtcatt ttcagaccag
     6361 gttaggagac gtgagctgct ctccacaaaa agcctcatgt gagtaataaa tgtttcatac
     6421 tctcttgggg tgtgtgtaac atcatcagtc tcagcatcta aaccaaattt tggtgacatt
     6481 tcatcttgtt tatgcagatg tccaccacac ctataaataa acaaactact gaaactgatt
     6541 caagaaaaaa taaaaatctg aatagagcta tcacaagtaa agagattaaa taagcaatca
     6601 aataacttcc cagaaagaaa agcccaattt aggatgtctt aactgattaa tgttagcaaa
     6661 tatttaaaga agaattggta caaattcttc acaaactctt ccagaaatgg aagaggagga
     6721 aacactttcc accttatttt ctataactag tattaccttg ataccaaatt ctgacaaata
     6781 catcaaaaat aaaaccatag accaatatct cttttaagtg taaatgcaaa aaaattcaac
     6841 aaaatgctag ataactgggt ccaacaacat atggaaagga ttatatacct tgaccaagtg
     6901 ggatttgccc caggaatgca agattgattt aaccatcagt gtaatgcatc atattaatag
     6961 aataaagaca gaaaccacac aatcatctcg atacacgcag aaaaatcatt tggcaaaatt
     7021 caacacccct ttgtaataaa atcactcaac acactaggaa gagaagggaa cttcttcaac
     7081 ctcacacatg gcatctatga aaaacccaca gctggccggg tatggtggct caagcctgta
     7141 atcccagcac tttgggaggc tgagccaggc ggatcacctg aggtcaggag ttcgagacca
     7201 acctgaccaa catggagaaa ccctgtatct actaaaaata caaaaaatta gcccggcgtg
     7261 gtggcaaatg cctgtaatcc cagctgcttg ggaggctgag gcaggagaat cggttgaacc
     7321 caggaggtgg aggttctggt gagccgagat cacgccattg tactccagcc tgggcaacaa
     7381 gaacaaaact ctgtctcaaa aaaaaaaaaa aaaagaaaag aaaaacccac agctaacatc
     7441 atacttaaag gtgaaagact gaaagctttc ccccaagagg aactaacagg atatctgctg
     7501 tcactatttt tattcaatat tatactggag gttctaccta gggtaattag gcaaaaaaaa
     7561 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aagaaaagaa aaaagtcatc
     7621 cagattggaa aagaaataaa atgatttcaa ttttaagatg acataatatt gtatgtagaa
     7681 atcctaagga atttacaaaa gaactattag agctaataca tgatttcagc aaggttgcag
     7741 gatacaagat caacatacag atataaattg tattctacac acttgtaatg aaaaatctga
     7801 aaataaaatt aagaaaatag caccctttga atagtatcaa aaagaataaa atacatagaa
     7861 aaaatgtaac aggaagtgca agactggtac attgaaaaca ataaaacatt gttaaaaaat
     7921 ttaaaatcat caaaatagat ggaaataaaa cctgtgttca tggatgaaaa aaattaacat
     7981 tgctctacag attcaataca attcttatca aaatcccagg tggcttaaga aattgacaag
     8041 ttaatcctaa aattcataag aaattgaaag ggatccacaa tagccaaaat aatcttaaaa
     8101 aagattttaa aaagttggag aactcacact tcctggtttc ataacataca ccaggctggg
     8161 catggtggtt catgcccata atcccagcac tttgggaagt tgaggcagaa ggatcacttg
     8221 agcacaggag tttgagacca gcctggacga tatagtgaga ccttgtctct actaaaaatt
     8281 taaaaaggaa ttagccaggt gtggtaacat gcacctgttg tcccagctac ttaggaggct
     8341 gaggcatgag gatcacttga gcccagaaga ttgtaccact gcactccagc ctacatgaca
     8401 gagtaagtct ctgtctcaaa aacaaaacaa acaacaaaaa tactgaaagc tttccccata
     8461 caggaactaa caggatatct gctgtcacta tttttattca atattgttct ggaggttcta
     8521 gctagggcaa ttaggcaaaa aaaggaaaaa gaagtcatcc agattagaaa agaaataaaa
     8581 taatttcaat tttcagatga cataatattg tatgtagaaa tcctaaggaa tttacaaaag
     8641 aactgctacc ctgaaagaat tgttgtaagg caaatacccc tgtaattacc attaggggaa
     8701 gaaatttttc catgcttcac agaaactctc cttatacccc acctcaattt taatcttttt
     8761 ctgtaccact acagttataa ttctcctaaa gcttaaagca attacctcct tgtttatatt
     8821 tatagtttca tcactgaagt gtgcattcct aaactcaaca ccttagtctg gttgcaaaca
     8881 gtttaaatga gaaaagataa ggcctgaatt aaggcagcag ccctaaacct ttttctataa
     8941 tcctgatagt gattaccacc taggggatta taaatgtttg cttcttcctc tggcaccaac
     9001 aagtttactg agcagaagtt taaaataatt ggataatggg gcaggtgaca tcagcaagat
     9061 gttgtattag caaatgctgg acccttcttc aatccacaaa cacatctatt ctgcaaaaat
     9121 tcatggctaa attcctttgt gaggaatcca gaaactaaaa ggctcctgca ctcccagcaa
     9181 atgcaaaaac cagactcacc aaagctggta gagagatttg agataccacc ttgtccgaat
     9241 ccctaacccc agcacagtgc catgtagtca gcaagagact ccctagcact cagtttctcc
     9301 caggtgagag gagttggttc acatatccaa gacctccaac ttttctgagg agattcccag
     9361 aggactggct tctatcttgt cagtcttgga gctctgacag aattggtact atctagctac
     9421 ctggggaagg acagagacag aggtttagac cagtagatga catggcaccc tgccctctac
     9481 tgcctcacct cctggctcag cacagacagg acaaaaatca tggctaccta catttccctg
     9541 gagaaggaat gatttgttaa aggcccccaa atcactgggc agacttattg gtgggggtct
     9601 tctcctctga ggcccagctg tgaggactgg gacaggtgac tgctttgtct aatgtgcaga
     9661 caccaacaca aagagtcaag gaaaatgaat aatcatacga agatgttcca aaccaaagaa
     9721 caagataaat ctctggaaac tgagctaatg aaataaactt atgtgattta cctgacagag
     9781 aattcagaat agctctcata aagattctca ccagagtcaa gagaacaatg catgaaaaaa
     9841 gttaagaatt ttgacaaaga gatagagtat atttaaaagt accaaaaaga aatggaactg
     9901 aagaacacaa caactgaact gaaaaaattt atgacaggac atcaacagga gacaagatta
     9961 atcagaagaa agaatcaatg aacttgaaga caggtcattg gaaataattc agttagagga
    10021 gaaattaaaa tgaaaaagag tgaaaaaaag cccaagggtc ttatgggcaa catcaagctg
    10081 aacaatatac tcattattgg catcacagaa taaaagagag aaaagaactg agaacgtatt
    10141 caaagaaata atggctgaac acttcccaaa tatgaggaag aaaatgaaca ttctgatcca
    10201 agaagcccaa aggtcataaa aaagtgatcc caaagcctac aggcatatta taagttgtca
    10261 tcctagagaa agaaaaatat ctttctccca gcctccatat tcaaatctta aggaaaattc
    10321 ttatggactt agcttgagtt tcaagttcat ttctaaaatc aatcatggtg gccaaacgga
    10381 atgagcattc tgatttgcca gtgtggtctc atgttacccc tgtgcctaga aaggaaacag
    10441 gagatgaaaa gcatggtgat aagaagactg gatggcacca catgggatag ggggaaagta
    10501 gttgaaaaaa aatagttgta aggaaaagag atacaaggag tcaaaaataa caaatatcta
    10561 cttaaaagcc ttttccacat ttaatgtttt ttgttcactg tggtgtagta ataaatgtct
    10621 atacttaagg ggtgaggatt gatatattta aagtgaatgg tctggaaggc aaggaagctc
    10681 attccaacag attcatgcta cattgtttag tgacaaataa ggggaacaga acagagaaag
    10741 tgatttcagc tataaatata ggagataata aaatccttta gtaaacagta tctaagcctt
    10801 gtttttatga tattggggaa cagtaacaga tcaaagtact gtagtcttca gtatgcagac
    10861 ctttcacttt cttagtttat tccagggtct tttttttttt tgctgctatt acaaatagca
    10921 ttgttttcct aatttttgtt taagatagtt catcgttggt atagaaatgc cattgatttt
    10981 tgtatgttga ttttgtatcc tccaacttta ctgaatttat tagttctaac agttttttga
    11041 tggagtcttt agggttttct atgtataaga ttatgtcatc tgcaaacagc aacaatttta
    11101 ccctttgttt tcaacgtgag cgtcttttat ttatttttct tgcctaattg ctttagctag
    11161 gacttccagc actaaattga atagaagtga tgagagtggg catgtatgcc ttgtttctgg
    11221 tcttaaagaa aaacatttca gttttccatt attcggtata atgttagtta tgggttttta
    11281 aaaatatata tgacctttat taggttgagg tacttttcct ctattcttag tttattgaat
    11341 gtttttctca tgaaagtgtg ttaaattttg tcaaaacctt ttttacatcc atcaaatgat
    11401 tatgtaattt ttatccttta ttctgttaat ggattatcac attaactaat tttcatatct
    11461 tgaagcatac ttgcatccta ggaataaatc ccactttgtc atagtctttg atccttttaa
    11521 tataatgtta aatttggttt gccagtattt tgttgaggat ttttgcatct atatattcat
    11581 caaggatatt gggctgtaat tttcttttct tgtggtgtct ttgtccggct ttagtataaa
    11641 ggtaattctg gcttcataaa ataagttaga aagtgttctc tcttctttga tttttttgga
    11701 agagtttgag aataattggc attagttttg ttaaatgttt ggttgaattc actagtgaaa
    11761 ttatttggtc ctgggatttt ctttactggg agttttttga ttacttgttc aatctttacg
    11821 ctagtcatag gtctgtccag tctttgtatt tcttcatgat ttagtcatca tgtattcatg
    11881 ggttgtaaga cttaatattc ttaaaatgcc catattaccc aaagtgatct atagattcat
    11941 gcaatcccca tcaaaaatcc cagtggcatt tttatttaca gaaatagaat aattctaaaa
    12001 ttcatctgaa gccacaaaag acaatgaata aacaaatcaa tcttgaaaaa gaagaacaaa
    12061 gctggaggca ttatacttcc tgatttcaaa atatcctgca aaggtacagt aatcaaaaca
    12121 gtatgttacc agcataaaga caaacacaca gaccaataga acagaataga gagctcagca
    12181 acaaatccgt gaatatacag tcaactgaca tttggcaatg gtgccaagca tactcagtgg
    12241 gagaaatgat aatctcttca acaaatggtg ttgggaaaac tgaatatcca catgcaaaag
    12301 aataaaattg gaccctatct tataccaaaa atcaactcaa aatggattat ttaaatgtaa
    12361 gacttgaaac agtaaaactc ctagaagtaa acagaagaga aagtttcatg acattgccct
    12421 tggcaatgat ttcatgtaca taacaacaaa agcacaggta ataaaaacaa aaatagacaa
    12481 atgggactac ctcaaattaa aatgtttctg cacagcaaac gaccaactga atgaaaaggc
    12541 aatctatgga acagaagaca cggggtgaca tgagaccact ttggcaaatc agaatgctca
    12601 ttccatttgg ccaccatgat tggttttaga aatggacttg aagctcaaag aaagcccata
    12661 atatattcct taagatttga atatagaggc tggaagaaag atttttttct ttctctagga
    12721 tgacaagtta tatataataa gcctgtaggc caatatctgc tggcagccac ctttcccagg
    12781 tatatggatg aaactatctg aaggatgaag cctccattca cagaaaatca gagctgtaaa
    12841 gggaagagga tatcctgatg aatttttttc ttggattgag ccatgtctga agtcaagcca
    12901 acttttgaag tatcctatag tacttatata ttgcttggta acaaattatg ccaaaattta
    12961 gtagcttaaa acaacaaaca tctattatct catgcatttc tgatatagat ataggagtga
    13021 ctaatctggg tggttctggg tcagaatctc tggtgagtgt gtaggcaagg tgtcagtagg
    13081 gggctgcaat tatctaaagg cttgcctggg gctggagacg cactttcaat gtggtgtact
    13141 cacgtggctg ttggttggag gccaaatgtg ctaggcaaag cctcatgcac atttctctgt
    13201 aaggaaacaa agctggctta cttgggggca ggattttttt ttttcccagt tgttcttcaa
    13261 aatgaagttt cccgctccaa gtcccagcca gatatgtgaa aaacaatcct tgcagaacaa
    13321 ccctattagc agttctgcaa ggatttttag gaaccgtatt agcaagttcc tcagttcctc
    13381 accatgtgaa cctctcttca cgacttagta actggcttcc tctagagtga ctaatccaag
    13441 agacagcaag gattgacagc catgacagca cagtgccttt catgacttac tctccaaagt
    13501 tacaaacctt tacttttgct ttatcttatt tgttagagca agtcactaaa tttgcccaca
    13561 tctaagatga gggtatttgg gcttcacctc ttgaatggag aagcacccaa aaatctgtgg
    13621 cctttttttt taattacact ctcagttaca tgaatcaata aattccattt ttggcttagc
    13681 ttctattggg tttctatcac ttgcaaccaa agtgccctaa ccagtatcta catctgagtc
    13741 attaagaaag tttcagacag ggctgggcgc ggtggctcac acctgttaat cccagacttt
    13801 gggaggccga ggcaggcgga tcacgtggtc aggagatcga gaccatcctg gctaacacgg
    13861 tgaaacctta tctctactaa aaatacaaaa aattagccgg gtgtggtggc aggtgcctga
    13921 agtcccagct actcgggagg ctgaggcagg ggaatggcgt gaacccggga gacggagctt
    13981 gcagtgagcc gagatcacgc cactgcgctc cagcctgggc gacagagtga gactcagctt
    14041 caaaaaaaaa aaaaaaaaag aaagtttcag atattattgt ttattgcttt taatctagtg
    14101 aattcataaa tcgtcactta actcaagcaa aacaatgtta ctctctttgt acattgtaca
    14161 gatgcaggat aacaatgcag tgttatcctg catctgtaca atcaagcacc caaactggtt
    14221 ctgtagaggc aggaccttag catatagcag agataactta tcttccagca gatccggagc
    14281 tccattttgt agacagaaat gaatgctctg tgccacagaa ggagctgttg cactattcat
    14341 tcccgtttcc tcccattcac tctccacatc tccaatcctg gcattgtctg ctttgttact
    14401 tgttaaaaac ttgatttcgt agattgcttt aaaataagaa caaaatgtac tttgacacac
    14461 atcattttgt ttggttctca ttaattttga gagaaaggca agatagatat ttaaatgacc
    14521 cctattttag tggtaaacaa gctgaaatta gataaataaa atgatttgcc taatg
//
