LOCUS       NM_001297732            6824 bp    mRNA    linear   PRI 05-DEC-2024
DEFINITION  Homo sapiens cytochrome c oxidase assembly factor COX18 (COX18),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_001297732 XM_005265679
VERSION     NM_001297732.2
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 6824)
  AUTHORS   Ronchi,D., Garbellini,M., Magri,F., Menni,F., Meneri,M.,
            Bedeschi,M.F., Dilena,R., Cecchetti,V., Picciolli,I., Furlan,F.,
            Polimeni,V., Salani,S., Pezzoli,L., Fortunato,F., Bellini,M.,
            Piga,D., Ripolone,M., Zanotti,S., Napoli,L., Ciscato,P.,
            Sciacco,M., Mangili,G., Mosca,F., Corti,S., Iascone,M. and
            Comi,G.P.
  TITLE     A biallelic variant in COX18 cause isolated Complex IV deficiency
            associated with neonatal encephalo-cardio-myopathy and axonal
            sensory neuropathy
  JOURNAL   Eur J Hum Genet 31 (12), 1414-1420 (2023)
   PUBMED   37468577
  REMARK    GeneRIF: A biallelic variant in COX18 cause isolated Complex IV
            deficiency associated with neonatal encephalo-cardio-myopathy and
            axonal sensory neuropathy.
REFERENCE   2  (bases 1 to 6824)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   3  (bases 1 to 6824)
  AUTHORS   Bourens,M. and Barrientos,A.
  TITLE     Human mitochondrial cytochrome c oxidase assembly factor COX18 acts
            transiently as a membrane insertase within the subunit 2 maturation
            module
  JOURNAL   J Biol Chem 292 (19), 7774-7783 (2017)
   PUBMED   28330871
  REMARK    GeneRIF: COX20 stabilizes COX2 during insertion of its N-proximal
            transmembrane domain, and subsequently, COX18 transiently interacts
            with COX2 to promote translocation across the inner membrane of the
            COX2 C-tail that contains the apo-CuA site. The release of COX18
            from this complex coincides with the binding of the SCO1-SCO2-COA6
            copper metallation module to COX2-COX20 to finalize COX2
            biogenesis.
REFERENCE   4  (bases 1 to 6824)
  AUTHORS   Al Olama,A.A., Kote-Jarai,Z., Berndt,S.I., Conti,D.V.,
            Schumacher,F., Han,Y., Benlloch,S., Hazelett,D.J., Wang,Z.,
            Saunders,E., Leongamornlert,D., Lindstrom,S., Jugurnauth-Little,S.,
            Dadaev,T., Tymrakiewicz,M., Stram,D.O., Rand,K., Wan,P., Stram,A.,
            Sheng,X., Pooler,L.C., Park,K., Xia,L., Tyrer,J., Kolonel,L.N., Le
            Marchand,L., Hoover,R.N., Machiela,M.J., Yeager,M., Burdette,L.,
            Chung,C.C., Hutchinson,A., Yu,K., Goh,C., Ahmed,M., Govindasami,K.,
            Guy,M., Tammela,T.L., Auvinen,A., Wahlfors,T., Schleutker,J.,
            Visakorpi,T., Leinonen,K.A., Xu,J., Aly,M., Donovan,J.,
            Travis,R.C., Key,T.J., Siddiq,A., Canzian,F., Khaw,K.T.,
            Takahashi,A., Kubo,M., Pharoah,P., Pashayan,N., Weischer,M.,
            Nordestgaard,B.G., Nielsen,S.F., Klarskov,P., Roder,M.A.,
            Iversen,P., Thibodeau,S.N., McDonnell,S.K., Schaid,D.J.,
            Stanford,J.L., Kolb,S., Holt,S., Knudsen,B., Coll,A.H.,
            Gapstur,S.M., Diver,W.R., Stevens,V.L., Maier,C., Luedeke,M.,
            Herkommer,K., Rinckleb,A.E., Strom,S.S., Pettaway,C., Yeboah,E.D.,
            Tettey,Y., Biritwum,R.B., Adjei,A.A., Tay,E., Truelove,A., Niwa,S.,
            Chokkalingam,A.P., Cannon-Albright,L., Cybulski,C., Wokolorczyk,D.,
            Kluzniak,W., Park,J., Sellers,T., Lin,H.Y., Isaacs,W.B.,
            Partin,A.W., Brenner,H., Dieffenbach,A.K., Stegmaier,C., Chen,C.,
            Giovannucci,E.L., Ma,J., Stampfer,M., Penney,K.L., Mucci,L.,
            John,E.M., Ingles,S.A., Kittles,R.A., Murphy,A.B., Pandha,H.,
            Michael,A., Kierzek,A.M., Blot,W., Signorello,L.B., Zheng,W.,
            Albanes,D., Virtamo,J., Weinstein,S., Nemesure,B., Carpten,J.,
            Leske,C., Wu,S.Y., Hennis,A., Kibel,A.S., Rybicki,B.A.,
            Neslund-Dudas,C., Hsing,A.W., Chu,L., Goodman,P.J., Klein,E.A.,
            Zheng,S.L., Batra,J., Clements,J., Spurdle,A., Teixeira,M.R.,
            Paulo,P., Maia,S., Slavov,C., Kaneva,R., Mitev,V., Witte,J.S.,
            Casey,G., Gillanders,E.M., Seminara,D., Riboli,E., Hamdy,F.C.,
            Coetzee,G.A., Li,Q., Freedman,M.L., Hunter,D.J., Muir,K.,
            Gronberg,H., Neal,D.E., Southey,M., Giles,G.G., Severi,G.,
            Cook,M.B., Nakagawa,H., Wiklund,F., Kraft,P., Chanock,S.J.,
            Henderson,B.E., Easton,D.F., Eeles,R.A. and Haiman,C.A.
  CONSRTM   Breast and Prostate Cancer Cohort Consortium (BPC3); PRACTICAL
            (Prostate Cancer Association Group to Investigate Cancer-Associated
            Alterations in the Genome) Consortium; COGS (Collaborative
            Oncological Gene-environment Study) Consortium; GAME-ON/ELLIPSE
            Consortium
  TITLE     A meta-analysis of 87,040 individuals identifies 23 new
            susceptibility loci for prostate cancer
  JOURNAL   Nat Genet 46 (10), 1103-1109 (2014)
   PUBMED   25217961
REFERENCE   5  (bases 1 to 6824)
  AUTHORS   Eeles,R.A., Olama,A.A., Benlloch,S., Saunders,E.J.,
            Leongamornlert,D.A., Tymrakiewicz,M., Ghoussaini,M., Luccarini,C.,
            Dennis,J., Jugurnauth-Little,S., Dadaev,T., Neal,D.E., Hamdy,F.C.,
            Donovan,J.L., Muir,K., Giles,G.G., Severi,G., Wiklund,F.,
            Gronberg,H., Haiman,C.A., Schumacher,F., Henderson,B.E., Le
            Marchand,L., Lindstrom,S., Kraft,P., Hunter,D.J., Gapstur,S.,
            Chanock,S.J., Berndt,S.I., Albanes,D., Andriole,G., Schleutker,J.,
            Weischer,M., Canzian,F., Riboli,E., Key,T.J., Travis,R.C.,
            Campa,D., Ingles,S.A., John,E.M., Hayes,R.B., Pharoah,P.D.,
            Pashayan,N., Khaw,K.T., Stanford,J.L., Ostrander,E.A.,
            Signorello,L.B., Thibodeau,S.N., Schaid,D., Maier,C., Vogel,W.,
            Kibel,A.S., Cybulski,C., Lubinski,J., Cannon-Albright,L.,
            Brenner,H., Park,J.Y., Kaneva,R., Batra,J., Spurdle,A.B.,
            Clements,J.A., Teixeira,M.R., Dicks,E., Lee,A., Dunning,A.M.,
            Baynes,C., Conroy,D., Maranian,M.J., Ahmed,S., Govindasami,K.,
            Guy,M., Wilkinson,R.A., Sawyer,E.J., Morgan,A., Dearnaley,D.P.,
            Horwich,A., Huddart,R.A., Khoo,V.S., Parker,C.C., Van As,N.J.,
            Woodhouse,C.J., Thompson,A., Dudderidge,T., Ogden,C., Cooper,C.S.,
            Lophatananon,A., Cox,A., Southey,M.C., Hopper,J.L., English,D.R.,
            Aly,M., Adolfsson,J., Xu,J., Zheng,S.L., Yeager,M., Kaaks,R.,
            Diver,W.R., Gaudet,M.M., Stern,M.C., Corral,R., Joshi,A.D.,
            Shahabi,A., Wahlfors,T., Tammela,T.L., Auvinen,A., Virtamo,J.,
            Klarskov,P., Nordestgaard,B.G., Roder,M.A., Nielsen,S.F.,
            Bojesen,S.E., Siddiq,A., Fitzgerald,L.M., Kolb,S., Kwon,E.M.,
            Karyadi,D.M., Blot,W.J., Zheng,W., Cai,Q., McDonnell,S.K.,
            Rinckleb,A.E., Drake,B., Colditz,G., Wokolorczyk,D.,
            Stephenson,R.A., Teerlink,C., Muller,H., Rothenbacher,D.,
            Sellers,T.A., Lin,H.Y., Slavov,C., Mitev,V., Lose,F.,
            Srinivasan,S., Maia,S., Paulo,P., Lange,E., Cooney,K.A.,
            Antoniou,A.C., Vincent,D., Bacot,F., Tessier,D.C., Kote-Jarai,Z.
            and Easton,D.F.
  CONSRTM   COGS-Cancer Research UK GWAS-ELLIPSE (part of GAME-ON) Initiative;
            Australian Prostate Cancer Bioresource; UK Genetic Prostate Cancer
            Study Collaborators/British Association of Urological Surgeons'
            Section of Oncology; UK ProtecT (Prostate testing for cancer and
            Treatment) Study Collaborators; PRACTICAL (Prostate Cancer
            Association Group to Investigate Cancer-Associated Alterations in
            the Genome) Consortium
  TITLE     Identification of 23 new prostate cancer susceptibility loci using
            the iCOGS custom genotyping array
  JOURNAL   Nat Genet 45 (4), 385-391 (2013)
   PUBMED   23535732
REFERENCE   6  (bases 1 to 6824)
  AUTHORS   Zhang,X., Yang,H., Lee,J.J., Kim,E., Lippman,S.M., Khuri,F.R.,
            Spitz,M.R., Lotan,R., Hong,W.K. and Wu,X.
  TITLE     MicroRNA-related genetic variations as predictors for risk of
            second primary tumor and/or recurrence in patients with early-stage
            head and neck cancer
  JOURNAL   Carcinogenesis 31 (12), 2118-2123 (2010)
   PUBMED   20819778
  REMARK    GeneRIF: Observational study of gene-disease association and
            gene-gene interaction. (HuGE Navigator)
REFERENCE   7  (bases 1 to 6824)
  AUTHORS   Karasik,D., Hsu,Y.H., Zhou,Y., Cupples,L.A., Kiel,D.P. and
            Demissie,S.
  TITLE     Genome-wide pleiotropy of osteoporosis-related phenotypes: the
            Framingham Study
  JOURNAL   J Bone Miner Res 25 (7), 1555-1563 (2010)
   PUBMED   20200953
  REMARK    GeneRIF: Observational study and genome-wide association study of
            gene-disease association. (HuGE Navigator)
REFERENCE   8  (bases 1 to 6824)
  AUTHORS   Sacconi,S., Salviati,L. and Trevisson,E.
  TITLE     Mutation analysis of COX18 in 29 patients with isolated cytochrome
            c oxidase deficiency
  JOURNAL   J Hum Genet 54 (7), 419-421 (2009)
   PUBMED   19373256
  REMARK    GeneRIF: COX18 mutations may be very rare or associated with other
            phenotypes than isolated COX deficiency in infancy.
REFERENCE   9  (bases 1 to 6824)
  AUTHORS   Gaisne,M. and Bonnefoy,N.
  TITLE     The COX18 gene, involved in mitochondrial biogenesis, is
            functionally conserved and tightly regulated in humans and fission
            yeast
  JOURNAL   FEMS Yeast Res 6 (6), 869-882 (2006)
   PUBMED   16911509
REFERENCE   10 (bases 1 to 6824)
  AUTHORS   Sacconi,S., Trevisson,E., Pistollato,F., Baldoin,M.C.,
            Rezzonico,R., Bourget,I., Desnuelle,C., Tenconi,R., Basso,G.,
            DiMauro,S. and Salviati,L.
  TITLE     hCOX18 and hCOX19: two human genes involved in cytochrome c oxidase
            assembly
  JOURNAL   Biochem Biophys Res Commun 337 (3), 832-839 (2005)
   PUBMED   16212937
  REMARK    GeneRIF: Both hCox18p and hCox19p present significant amino acid
            identity with the corresponding yeast polypeptides and reveal
            highly conserved functional domains.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA385228.1, BC143642.1 and
            AC095053.3.
            
            On Jun 2, 2019 this sequence version replaced NM_001297732.1.
            
            Summary: This gene encodes a cytochrome c oxidase assembly protein.
            The encoded protein is essential for integral membrane protein
            insertion into the mitochondrial inner membrane. It is also
            required for cytochrome c oxidase assembly and activity.
            Alternative splicing results in multiple transcript variants.
            [provided by RefSeq, Jul 2014].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes 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 :: SRR1803612.205678.1, BC143642.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000507544.3/
                                                  ENSP00000425261.3
            RefSeq Select criteria             :: based on manual assertion,
                                                  conservation
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-24                DA385228.1         44-67
            25-1110             BC143642.1         1-1086
            1111-6824           AC095053.3         72734-78447         c
FEATURES             Location/Qualifiers
     source          1..6824
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="4"
                     /map="4q13.3"
     gene            1..6824
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /note="cytochrome c oxidase assembly factor COX18"
                     /db_xref="GeneID:285521"
                     /db_xref="HGNC:HGNC:26801"
                     /db_xref="MIM:610428"
     exon            1..400
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /inference="alignment:Splign:2.1.0"
     CDS             68..1072
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /note="isoform 1 is encoded by transcript variant 1;
                     mitochondrial inner membrane protein COX18; cytochrome c
                     oxidase assembly protein 18; COX18, cytochrome c oxidase
                     assembly factor; cytochrome c oxidase assembly homolog 18;
                     cytochrome c oxidase assembly protein COX18,
                     mitochondrial"
                     /codon_start=1
                     /product="cytochrome c oxidase assembly protein COX18,
                     mitochondrial isoform 1"
                     /protein_id="NP_001284661.1"
                     /db_xref="CCDS:CCDS75139.1"
                     /db_xref="GeneID:285521"
                     /db_xref="HGNC:HGNC:26801"
                     /db_xref="MIM:610428"
                     /translation="MLCRLGGRWLRPLPALQLWARDLPLAPVPTSGAKRPTLPVWAVA
                     PVSAVHANGWYEALAASSPVRVAEEVLLGVHAATGLPWWGSILLSTVALRGAVTLPLA
                     AYQHYILAKVENLQPEIKTIARHLNQEVAVRANQLGWSKRDARLTYLKNMRRLISELY
                     VRDNCHPFKATVLVWIQLPMWIFMSFALRNLSTGAAHSEAGFSVQEQLATGGILWFPD
                     LTAPDSTWILPISVGVINLLIVEICALQKIGMSRFQTYITYFVRAMSVLMIPIAATVP
                     SSIVLYWLCSSFVGLSQNLLLRSPGFRQLCRIPSTKSDSETPYKDIFAAFNTKFISRK
                     "
     exon            401..501
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            502..665
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            666..790
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            791..898
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /inference="alignment:Splign:2.1.0"
     exon            899..6824
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2507..2512
                     /regulatory_class="polyA_signal_sequence"
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /note="hexamer: AATAAA"
     polyA_site      2528
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /note="major polyA site"
     regulatory      3084..3089
                     /regulatory_class="polyA_signal_sequence"
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /note="hexamer: AATAAA"
     polyA_site      3106
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
     regulatory      4462..4467
                     /regulatory_class="polyA_signal_sequence"
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /note="hexamer: AATGAA"
     polyA_site      4486
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
     regulatory      6704..6709
                     /regulatory_class="polyA_signal_sequence"
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /note="hexamer: ATTAAA"
     polyA_site      6734
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
     regulatory      6806..6811
                     /regulatory_class="polyA_signal_sequence"
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
                     /note="hexamer: AATACA"
     polyA_site      6824
                     /gene="COX18"
                     /gene_synonym="COX18HS; OXA1L2"
ORIGIN      
        1 cttggctggc cggtgtatgt ccgctggatt gtgaggcccg ggatctgggc tccgccgtgg
       61 tgcagaaatg ctgtgccggc tcggcggtcg gtggctgcgg ccgctccctg ccctgcagct
      121 ttgggctagg gacctgccgc ttgcgccggt tcctacgagc ggcgccaagc gccccactct
      181 cccagtgtgg gcagtggcac cagtctctgc agtacatgcg aacggctggt acgaggccct
      241 ggccgcgtct tcgccggtgc gggttgcgga ggaagtactg ctcggcgtgc acgccgccac
      301 gggcctgccc tggtggggca gcattctgct ctccaccgtg gccttacggg gtgctgtcac
      361 gctgcctttg gcagcctacc agcactacat cctggccaag gtggaaaatt tgcagccaga
      421 aataaaaact attgccaggc atcttaacca agaagttgca gttcgtgcaa atcagttggg
      481 gtggtccaaa agagatgcca ggctcactta tctaaagaat atgaggaggc taatttcaga
      541 gctatatgtg cgagataact gccacccttt caaagccact gtgttggttt ggattcagct
      601 tccaatgtgg atcttcatgt cttttgctct ccggaattta agcacggggg cagcacattc
      661 agaagcaggt ttttctgttc aggaacagtt agctactggt ggaattctgt ggtttcctga
      721 cctcactgca cccgactcca cttggattct gcctatctct gttggcgtca tcaatttgtt
      781 aatagtggag atttgtgctc tacaaaaaat tggaatgtct cgttttcaga cgtatattac
      841 gtactttgtc cgtgcaatgt cggtgttgat gataccaatt gctgcaacgg taccctcatc
      901 aattgttctc tactggttat gctccagctt cgtgggcctt tcacagaatt tgctgctgcg
      961 ttctcctgga tttcgccaac tttgccgaat accatcgacc aagtcagatt cagaaactcc
     1021 ttataaagac atatttgctg cctttaatac caagttcatt tcaagaaaat gacatatttt
     1081 ccaataattt tgaaacagtt gcaggagtca ctatcatcta aatgtattta gacttagaaa
     1141 ttcagatgtt acttgatttc cttttattta aaatcattaa cttcatgaaa tattgtaggt
     1201 taagatgtaa tccagaccag gcacagtggc tcatgcctgt aatcccagca ctttgggagg
     1261 tcgaggtggg tggatcacct gaggtctgga gtttgagacc agcctggcca acatggtgaa
     1321 accctgtctg tactaaaata acaaaaaaat tagctgggct tagtggcagg tgcctgtaat
     1381 cccagctact tgggaggctg aggcaggaga atcgcttgaa cctggaatac agaggtttca
     1441 gtgagctgag atcaccccat tgcactccag cctggacaac aagagtgaaa cgctatcaaa
     1501 gaaaaaaaaa agatgtaatc cagatatatt tgacagtaat taaaatcttt taaatgttat
     1561 aaatgcagta tgtttgtgaa agtattagaa tagaaccaaa gtgcctgtct ctgtttataa
     1621 agttacagtt tgttagagct accagaactt tggagaatag ggttagctac tgaatgatgg
     1681 caagttaaac taaacaatac tgcatattac tgttttgtaa aataagagga tcagtgagat
     1741 gattcatgtt tttttttttt gagatggagt ctcactgtgt cacccaggct ggagtgcagt
     1801 ggcgcaatct cagctcactg caacctccat ctcccggatt ccagtgattt tcctgcctca
     1861 gcctccaagt atctgggatt gcaggtgcac accaccacgc ccagctaatt tttgtatttt
     1921 tagtagagat ggggtttcac catgttggac aggctggtct ggaactgctg acctcaacta
     1981 atccaccctc cttggcctcc catagtgctg ggattacagg catgagccac ctcacccagc
     2041 attttttttt tttaattttt ttaatgagac agagtctctc tctgtcacct aggctggagt
     2101 gcagtggcac gatctcggct cactgcaacc tctgcctccc gtgttcaagc aattctccta
     2161 cctcagccta ctgggtagct gggactacag gggtgcacca ccatgcccag ctaagttttg
     2221 tatttttagt agagatggga tttcaccatg ttggctaggc tggtcttgaa ctcctggcct
     2281 caagtgatct gcccaccttg gcctcccaaa gtgctgggat tacaggcgtg agccactgtg
     2341 cccagctgag atgtttctta ttattttgga ggtggagagg attttagacc tctttgagca
     2401 tctgaaaaaa ggctatatat gtatggtttt ctcttcagaa aaatcttaag actcacaata
     2461 cggggacttc cttgttacca ggaagatttt ctggcaattc ctagttaata aatcttattc
     2521 taatggaaca tacattgatc ttgagttaat gcgtggttga aaaaaaaagc gggggcaact
     2581 tgaaatatat gcagtaaagt agtccatgca tacaagtccc taacatggta gatgatgttg
     2641 cctcccggcc ctgctcagaa agaatacaaa aagtgtacat tcctttttct ataatttaag
     2701 aagtctggaa tacagagtgt aacactgtgt actgctagca cccaaagtgg aaaatcttaa
     2761 gcattcagat tgtttagtca aagaagaaaa ccagaagggc agttgcctat tgaggtgatt
     2821 ttaaacctgt ttatttgtaa ggattaagta ccctaatagg cttaaactat gatagaggtt
     2881 taatacagaa aaaattgaca ggtattataa attgtggatc cagttacttg cttatttaat
     2941 ttgtaaagag gtaaaattag ctctggttga gatatcaagt atggcaggta tttgagaagg
     3001 ctataaatca taattttcat ttagttaaaa tatggacctg attctgggaa accctatcat
     3061 tccatctcaa tgttttacaa taaaataaaa actaaagtga aattcattag tcatttcttt
     3121 gattgatgtc tcttaaattt tagttcacct gcttaatgaa gttatgacat tttttaatag
     3181 aaaaaatgta cagcatacag aggtaagaat tctgcttccc tgagaattta ttttagacat
     3241 agatggtggc aattaagact aggttctttt ttcatacaag ttcctagtcc tggtttctga
     3301 ctgtcctatt ggggcaattg tgctttccaa ccacattgaa ggaattgaaa tatcctcatt
     3361 atttgtggat tttatatttg taaatttgcc tccttgctca aatctatcca taaccccaga
     3421 accagtactt gcacaagtgc ttttgagcca tttgtaggca aaaatgtgag tcacctccca
     3481 acagaagtga aacaaatggt actctgcctt ctagtttcag ctctcatacc gtaaacatgt
     3541 atcctttttg agtctactta gtcccatctc ttcctaattt ctgttctttt tgttggtgat
     3601 tttactgttt aaaatggcct ccaaatgccc tgctggagtg ctttctgatg ttcctaagct
     3661 caggaaggct taggagaaaa taagtatatt agataagctt cattcatgca caagttataa
     3721 tgctgttggc agagagttca gtgttactga atcaacaata tgttgcattg ttctgttgac
     3781 aaaaacaaag cttgcagaaa cctaaccctg tatgttttct aggagcagtg atttggtatt
     3841 cactacttca gtgtttgtgg actttatgga acataagtac cacaaataat gcaaattgac
     3901 tatatttgca gcgtgtacaa tcaaggatgc agaggcagaa atgtgtgtgc agcttaggtc
     3961 atagtaaaaa gaggaaagaa tttgaggaaa attttgccag ttacatatta cctctggaat
     4021 aactttgcct ttgccgtgtg tgttactgtg tacactcaga tatttttctc ataatggcct
     4081 ttgccgtgtg tgttactgag tgagtacact cagatatttt tctcataatg gcatgaggga
     4141 aatcagtctc cttttcccat tgtgtttgtc acttttgctg agacgcaaaa aataacgtgc
     4201 tatgatattg tgaaatatgt atttggtctt tatccccaat ccctgacatc cagcggaatc
     4261 tgcagagtta agtgtctttt gtatgctcat gtgatgactg gtggctgggg gcccctagaa
     4321 agtttcagga tagggcagat ccttgtggcc aggagttcca gatcagcctg ggcaacatag
     4381 tgagaccttg tctgtacaaa aaagaaagta ggaaaaaaca tctttggttt ttcctatctc
     4441 cagatacttc cttttcaaat aaatgaatct tctttcatgt gcataattta ccttgtttac
     4501 tgtgagtccc cttgatttca aaatgtatat ttgtatcttt acaaatgtat attgtgctta
     4561 gtttcctgtt gctctcccat tgtcaaactt tcaaacttga aatttctttt caaatatata
     4621 caggaagttt gagaatacaa ggcccttcct ccaagatctc aaaataattt ctcacaagtg
     4681 ggggttgctg ggatcttggg ataaacccat gtataaagaa aactggtgta ttatgaactg
     4741 aagtgaatca gttacctgaa cttacctgac ttcaggatgg taaatactct tgattttttt
     4801 cttcaggcag atttttttta gtaaagagca aaaaatctgt attgtatttc agaaaattgc
     4861 aagtctgtgg tcttatttct aacagtttgt catagcctgg agcagttcca gaacctgaat
     4921 gaagtcaggg ctacagaaca gggaatatgc atgctcttaa gaccccttga tgtcttgctg
     4981 tctggcttgc ctatatcccc tcagttgctg aggctctgcg ctgggccctg cagagttcag
     5041 gaaggttttt gtctccttag atgaggactg taatgtttgt gttacccttc cccacagggg
     5101 tgttacccac ccttctcgtc cttacaggag atctgttttt cctgtgggtc tcatttttgt
     5161 ctctaggcca gattcactgt cttaatgaat gcttctcatt tcaagagtca ggaagggaga
     5221 ctcactcctg gatcaattta tagtatttat accattagga tacctgagtt caaaagtata
     5281 ttaatagata gaattggcgt atctgaaatg atcccaaatt acttttccct gggaccgtta
     5341 gaagagaaaa ctgaacaaat cccatcctag tcagatgtcc taagtgggaa gatgaggctt
     5401 acaaaggaaa accaaaattc ttaattgcca ccctgacaga taacccagga gaaggtgcaa
     5461 agcctcatta agaacctcga gggaaaagcc aaacttgggg agaagacttt tcaggtacct
     5521 ttaacagcac ttaagagcta aagaccatat cttcatctaa gaaccaccca tttacccgtc
     5581 caaaccgaaa gaacagactt ggagacctga agaacagtgg aagcaagact tttaatggca
     5641 gtcttgcaag attgggtgtc tggtgggcag gcacacctgg ggcagttaca gcaggtaatt
     5701 tatctcctag cacacaagtc cttcccccag tttctgattg gttaagtact atgggattac
     5761 agtcttccca gacatcgcgt aagtttcatt atcccccttg taaggttata taccccattc
     5821 ccttcccccc ttaagttttg atttcccaat aacgaaactt tcttcccttt tatgggctga
     5881 ctcctcctct acattctgtt cgtttattgt gaccttctag gtgcatgagc agtgcggttt
     5941 gttacatacc aaggctggct gccagtgctt agatttatca tgccttgaaa atggaccatt
     6001 taaaatgttt tcccacagtt cacatctcag aggaggtaca gaggtcctcc tagatgacat
     6061 tgggaaaatt gtagttagtg tgaaaaaatg agtgcccaaa aaaaccttgg taccttctgt
     6121 gttttgttcc tatttttttt ttattggacg cataatctgc ttatattttg cacctattct
     6181 taaatcacac ttataccttc atattttatt cttctaagaa tcccaggaat cacctttttt
     6241 ttttttttag gagtcacctt taaaattgcc tatatgtcag atttaagtcc cagaagcagt
     6301 aggaatgcag accctagaaa aaaaattaaa gaatgtagtt tattttttcc tctggggtgt
     6361 taactgcagc tactacagaa tgcagacttt ggaatttcag gcataacatc tgaaaccatg
     6421 caagaattta gatttctgta ttaaagctaa atcttcatgt aaatatggtg taaaacaatg
     6481 cattatcatt ataaacactg tgccttacga gctggttcaa gcagaaccca gataattgga
     6541 aattatatga atttatagat tttccatttg aaccttatta gtgttgttta aacttgtaat
     6601 aatggatatt ttctagttat ctgttttctt tttttcatac actgtgatgg tattttatga
     6661 aatcatttgg ttttgggaag ttggaatttc ctaaagccac agcattaaag tcagataatt
     6721 ttatttaccc aaaagtttct ggaacgctgt ggttctgtac tgtgtataca actaaaataa
     6781 gaatataaat ttatataaaa ataaaaatac aactatataa gtaa
//
