LOCUS       NM_016953               9305 bp    mRNA    linear   PRI 06-JUN-2024
DEFINITION  Homo sapiens phosphodiesterase 11A (PDE11A), transcript variant 4,
            mRNA.
ACCESSION   NM_016953
VERSION     NM_016953.4
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 9305)
  AUTHORS   Faja,F., Finocchi,F., Carlini,T., Rizzo,F., Pallotti,F.,
            Spaziani,M., Balercia,G., Lenzi,A., Paoli,D. and Lombardo,F.
  TITLE     PDE11A gene polymorphism in testicular cancer: sperm parameters and
            hormonal profile
  JOURNAL   J Endocrinol Invest 44 (10), 2273-2284 (2021)
   PUBMED   33661511
  REMARK    GeneRIF: PDE11A gene polymorphism in testicular cancer: sperm
            parameters and hormonal profile.
REFERENCE   2  (bases 1 to 9305)
  AUTHORS   Qin,W., Zhou,A., Zuo,X., Jia,L., Li,F., Wang,Q., Li,Y., Wei,Y.,
            Jin,H., Cruchaga,C., Benitez,B.A. and Jia,J.
  TITLE     Exome sequencing revealed PDE11A as a novel candidate gene for
            early-onset Alzheimer's disease
  JOURNAL   Hum Mol Genet 30 (9), 811-822 (2021)
   PUBMED   33835157
  REMARK    GeneRIF: Exome sequencing revealed PDE11A as a novel candidate gene
            for early-onset Alzheimer's disease.
REFERENCE   3  (bases 1 to 9305)
  AUTHORS   Ohlsson,T., Lindgren,A., Engstrom,G., Jern,C. and Melander,O.
  TITLE     A stop-codon of the phosphodiesterase 11A gene is associated with
            elevated blood pressure and measures of obesity
  JOURNAL   J Hypertens 34 (3), 445-51 (2016)
   PUBMED   26820475
  REMARK    GeneRIF: One percent of the Swedish population carries a PDE11A
            loss-of-function mutation which is associated with elevated BP,
            abdominal obesity, and risk of ischemic stroke.
REFERENCE   4  (bases 1 to 9305)
  AUTHORS   Pathak,A., Stewart,D.R., Faucz,F.R., Xekouki,P., Bass,S., Vogt,A.,
            Zhang,X., Boland,J., Yeager,M., Loud,J.T., Nathanson,K.L.,
            McGlynn,K.A., Stratakis,C.A., Greene,M.H. and Mirabello,L.
  TITLE     Rare inactivating PDE11A variants associated with testicular germ
            cell tumors
  JOURNAL   Endocr Relat Cancer 22 (6), 909-917 (2015)
   PUBMED   26459559
  REMARK    GeneRIF: Testicular germ cell tumors had 55 PDE11A variants: 20
            missense (10 new, 9 in transcript variant 4, 1 in transcript
            variant 3), 4 splice-site, 2 nonsense, 7 synonymous, and 22
            intronic.  p.F258Y, p.G291R, p.V820M, p.R545X, and p.K568R were
            only in cases.
REFERENCE   5  (bases 1 to 9305)
  AUTHORS   den Hoed,M., Eijgelsheim,M., Esko,T., Brundel,B.J., Peal,D.S.,
            Evans,D.M., Nolte,I.M., Segre,A.V., Holm,H., Handsaker,R.E.,
            Westra,H.J., Johnson,T., Isaacs,A., Yang,J., Lundby,A., Zhao,J.H.,
            Kim,Y.J., Go,M.J., Almgren,P., Bochud,M., Boucher,G.,
            Cornelis,M.C., Gudbjartsson,D., Hadley,D., van der Harst,P.,
            Hayward,C., den Heijer,M., Igl,W., Jackson,A.U., Kutalik,Z.,
            Luan,J., Kemp,J.P., Kristiansson,K., Ladenvall,C., Lorentzon,M.,
            Montasser,M.E., Njajou,O.T., O'Reilly,P.F., Padmanabhan,S., St
            Pourcain,B., Rankinen,T., Salo,P., Tanaka,T., Timpson,N.J.,
            Vitart,V., Waite,L., Wheeler,W., Zhang,W., Draisma,H.H.,
            Feitosa,M.F., Kerr,K.F., Lind,P.A., Mihailov,E., Onland-Moret,N.C.,
            Song,C., Weedon,M.N., Xie,W., Yengo,L., Absher,D., Albert,C.M.,
            Alonso,A., Arking,D.E., de Bakker,P.I., Balkau,B., Barlassina,C.,
            Benaglio,P., Bis,J.C., Bouatia-Naji,N., Brage,S., Chanock,S.J.,
            Chines,P.S., Chung,M., Darbar,D., Dina,C., Dorr,M., Elliott,P.,
            Felix,S.B., Fischer,K., Fuchsberger,C., de Geus,E.J., Goyette,P.,
            Gudnason,V., Harris,T.B., Hartikainen,A.L., Havulinna,A.S.,
            Heckbert,S.R., Hicks,A.A., Hofman,A., Holewijn,S.,
            Hoogstra-Berends,F., Hottenga,J.J., Jensen,M.K., Johansson,A.,
            Junttila,J., Kaab,S., Kanon,B., Ketkar,S., Khaw,K.T., Knowles,J.W.,
            Kooner,A.S., Kors,J.A., Kumari,M., Milani,L., Laiho,P.,
            Lakatta,E.G., Langenberg,C., Leusink,M., Liu,Y., Luben,R.N.,
            Lunetta,K.L., Lynch,S.N., Markus,M.R., Marques-Vidal,P., Mateo
            Leach,I., McArdle,W.L., McCarroll,S.A., Medland,S.E., Miller,K.A.,
            Montgomery,G.W., Morrison,A.C., Muller-Nurasyid,M., Navarro,P.,
            Nelis,M., O'Connell,J.R., O'Donnell,C.J., Ong,K.K., Newman,A.B.,
            Peters,A., Polasek,O., Pouta,A., Pramstaller,P.P., Psaty,B.M.,
            Rao,D.C., Ring,S.M., Rossin,E.J., Rudan,D., Sanna,S., Scott,R.A.,
            Sehmi,J.S., Sharp,S., Shin,J.T., Singleton,A.B., Smith,A.V.,
            Soranzo,N., Spector,T.D., Stewart,C., Stringham,H.M., Tarasov,K.V.,
            Uitterlinden,A.G., Vandenput,L., Hwang,S.J., Whitfield,J.B.,
            Wijmenga,C., Wild,S.H., Willemsen,G., Wilson,J.F., Witteman,J.C.,
            Wong,A., Wong,Q., Jamshidi,Y., Zitting,P., Boer,J.M., Boomsma,D.I.,
            Borecki,I.B., van Duijn,C.M., Ekelund,U., Forouhi,N.G., Froguel,P.,
            Hingorani,A., Ingelsson,E., Kivimaki,M., Kronmal,R.A., Kuh,D.,
            Lind,L., Martin,N.G., Oostra,B.A., Pedersen,N.L., Quertermous,T.,
            Rotter,J.I., van der Schouw,Y.T., Verschuren,W.M., Walker,M.,
            Albanes,D., Arnar,D.O., Assimes,T.L., Bandinelli,S., Boehnke,M., de
            Boer,R.A., Bouchard,C., Caulfield,W.L., Chambers,J.C., Curhan,G.,
            Cusi,D., Eriksson,J., Ferrucci,L., van Gilst,W.H., Glorioso,N., de
            Graaf,J., Groop,L., Gyllensten,U., Hsueh,W.C., Hu,F.B.,
            Huikuri,H.V., Hunter,D.J., Iribarren,C., Isomaa,B., Jarvelin,M.R.,
            Jula,A., Kahonen,M., Kiemeney,L.A., van der Klauw,M.M.,
            Kooner,J.S., Kraft,P., Iacoviello,L., Lehtimaki,T., Lokki,M.L.,
            Mitchell,B.D., Navis,G., Nieminen,M.S., Ohlsson,C., Poulter,N.R.,
            Qi,L., Raitakari,O.T., Rimm,E.B., Rioux,J.D., Rizzi,F., Rudan,I.,
            Salomaa,V., Sever,P.S., Shields,D.C., Shuldiner,A.R., Sinisalo,J.,
            Stanton,A.V., Stolk,R.P., Strachan,D.P., Tardif,J.C.,
            Thorsteinsdottir,U., Tuomilehto,J., van Veldhuisen,D.J.,
            Virtamo,J., Viikari,J., Vollenweider,P., Waeber,G., Widen,E.,
            Cho,Y.S., Olsen,J.V., Visscher,P.M., Willer,C., Franke,L.,
            Erdmann,J., Thompson,J.R., Pfeufer,A., Sotoodehnia,N.,
            Newton-Cheh,C., Ellinor,P.T., Stricker,B.H., Metspalu,A.,
            Perola,M., Beckmann,J.S., Smith,G.D., Stefansson,K., Wareham,N.J.,
            Munroe,P.B., Sibon,O.C., Milan,D.J., Snieder,H., Samani,N.J. and
            Loos,R.J.
  CONSRTM   Global BPgen Consortium; CARDIoGRAM Consortium; PR GWAS Consortium;
            QRS GWAS Consortium; QT-IGC Consortium; CHARGE-AF Consortium
  TITLE     Identification of heart rate-associated loci and their effects on
            cardiac conduction and rhythm disorders
  JOURNAL   Nat Genet 45 (6), 621-631 (2013)
   PUBMED   23583979
REFERENCE   6  (bases 1 to 9305)
  AUTHORS   Hetman,J.M., Robas,N., Baxendale,R., Fidock,M., Phillips,S.C.,
            Soderling,S.H. and Beavo,J.A.
  TITLE     Cloning and characterization of two splice variants of human
            phosphodiesterase 11A
  JOURNAL   Proc Natl Acad Sci U S A 97 (23), 12891-12895 (2000)
   PUBMED   11050148
REFERENCE   7  (bases 1 to 9305)
  AUTHORS   Yuasa,K., Kotera,J., Fujishige,K., Michibata,H., Sasaki,T. and
            Omori,K.
  TITLE     Isolation and characterization of two novel phosphodiesterase
            PDE11A variants showing unique structure and tissue-specific
            expression
  JOURNAL   J Biol Chem 275 (40), 31469-31479 (2000)
   PUBMED   10906126
REFERENCE   8  (bases 1 to 9305)
  AUTHORS   Fawcett,L., Baxendale,R., Stacey,P., McGrouther,C., Harrow,I.,
            Soderling,S., Hetman,J., Beavo,J.A. and Phillips,S.C.
  TITLE     Molecular cloning and characterization of a distinct human
            phosphodiesterase gene family: PDE11A
  JOURNAL   Proc Natl Acad Sci U S A 97 (7), 3702-3707 (2000)
   PUBMED   10725373
REFERENCE   9  (bases 1 to 9305)
  AUTHORS   Loughney,K., Martins,T.J., Harris,E.A., Sadhu,K., Hicks,J.B.,
            Sonnenburg,W.K., Beavo,J.A. and Ferguson,K.
  TITLE     Isolation and characterization of cDNAs corresponding to two human
            calcium, calmodulin-regulated, 3',5'-cyclic nucleotide
            phosphodiesterases
  JOURNAL   J Biol Chem 271 (2), 796-806 (1996)
   PUBMED   8557689
REFERENCE   10 (bases 1 to 9305)
  AUTHORS   Beavo,J.A., Conti,M. and Heaslip,R.J.
  TITLE     Multiple cyclic nucleotide phosphodiesterases
  JOURNAL   Mol Pharmacol 46 (3), 399-405 (1994)
   PUBMED   7935318
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC011998.8, AB036704.1,
            BC112393.1, AC073834.6 and AI919276.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_016953.3.
            
            Summary: The 3',5'-cyclic nucleotides cAMP and cGMP function as
            second messengers in a wide variety of signal transduction
            pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs)
            catalyze the hydrolysis of cAMP and cGMP to the corresponding
            5'-monophosphates and provide a mechanism to downregulate cAMP and
            cGMP signaling. This gene encodes a member of the PDE protein
            superfamily. Mutations in this gene are a cause of Cushing disease
            and adrenocortical hyperplasia. Multiple transcript variants
            encoding different isoforms have been found for this gene.
            [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (4) represents the longest
            transcript and encodes the longest isoform (4).
            
            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 :: AB036704.1, BC112393.1 [ECO:0000332]
            RNAseq introns              :: mixed/partial sample support
                                           SAMEA1968189, SAMEA1968540
                                           [ECO:0000350]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000286063.11/ ENSP00000286063.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-22                AC011998.8         121356-121377       c
            23-890              AB036704.1         1-868
            891-1132            AC011998.8         120246-120487       c
            1133-3103           BC112393.1         1102-3072
            3104-3264           BC112393.1         3076-3236
            3265-8996           AC073834.6         116649-122380       c
            8997-9300           AI919276.1         8-311               c
            9301-9305           AC073834.6         116340-116344       c
FEATURES             Location/Qualifiers
     source          1..9305
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q31.2"
     gene            1..9305
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /note="phosphodiesterase 11A"
                     /db_xref="GeneID:50940"
                     /db_xref="HGNC:HGNC:8773"
                     /db_xref="MIM:604961"
     exon            1..1252
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     CDS             341..3142
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /EC_number="3.1.4.35"
                     /EC_number="3.1.4.53"
                     /note="isoform 4 is encoded by transcript variant 4; cAMP
                     and cGMP cyclic nucleotide phosphodiesterase 11A; dual
                     3',5'-cyclic-AMP and -GMP phosphodiesterase 11A"
                     /codon_start=1
                     /product="dual 3',5'-cyclic-AMP and -GMP phosphodiesterase
                     11A isoform 4"
                     /protein_id="NP_058649.3"
                     /db_xref="CCDS:CCDS33334.1"
                     /db_xref="GeneID:50940"
                     /db_xref="HGNC:HGNC:8773"
                     /db_xref="MIM:604961"
                     /translation="MAASRLDFGEVETFLDRHPELFEDYLMRKGKQEMVEKWLQRHSQ
                     GQGALGPRPSLAGTSSLAHSTCRGGSSVGGGTGPNGSAHSQPLPGGGDCGGVPLSPSW
                     AGGSRGDGNLQRRASQKELRKSFARSKAIHVNRTYDEQVTSRAQEPLSSVRRRALLRK
                     ASSLPPTTAHILSALLESRVNLPRYPPTAIDYKCHLKKHNERQFFLELVKDISNDLDL
                     TSLSYKILIFVCLMVDADRCSLFLVEGAAAGKKTLVSKFFDVHAGTPLLPCSSTENSN
                     EVQVPWGKGIIGYVGEHGETVNIPDAYQDRRFNDEIDKLTGYKTKSLLCMPIRSSDGE
                     IIGVAQAINKIPEGAPFTEDDEKVMQMYLPFCGIAISNAQLFAASRKEYERSRALLEV
                     VNDLFEEQTDLEKIVKKIMHRAQTLLKCERCSVLLLEDIESPVVKFTKSFELMSPKCS
                     ADAENSFKESMEKSSYSDWLINNSIAELVASTGLPVNISDAYQDPRFDAEADQISGFH
                     IRSVLCVPIWNSNHQIIGVAQVLNRLDGKPFDDADQRLFEAFVIFCGLGINNTIMYDQ
                     VKKSWAKQSVALDVLSYHATCSKAEVDKFKAANIPLVSELAIDDIHFDDFSLDVDAMI
                     TAALRMFMELGMVQKFKIDYETLCRWLLTVRKNYRMVLYHNWRHAFNVCQLMFAMLTT
                     AGFQDILTEVEILAVIVGCLCHDLDHRGTNNAFQAKSGSALAQLYGTSATLEHHHFNH
                     AVMILQSEGHNIFANLSSKEYSDLMQLLKQSILATDLTLYFERRTEFFELVSKGEYDW
                     NIKNHRDIFRSMLMTACDLGAVTKPWEISRQVAELVTSEFFEQGDRERLELKLTPSAI
                     FDRNRKDELPRLQLEWIDSICMPLYQALVKVNVKLKPMLDSVATNRSKWEELHQKRLL
                     ASTASSSPASVMVAKEDRN"
     exon            1253..1411
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            1412..1501
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            1502..1642
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            1643..1707
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            1708..1840
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            1841..1916
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            1917..1984
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            1985..2077
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2078..2128
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2129..2275
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2276..2383
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2384..2493
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2494..2584
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2585..2685
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2686..2763
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2764..2827
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2828..2902
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2903..2986
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     exon            2987..9305
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      8817..8822
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /note="hexamer: AATGAA"
     polyA_site      8843
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
     regulatory      9280..9285
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /note="hexamer: AATAAA"
     polyA_site      9305
                     /gene="PDE11A"
                     /gene_synonym="PPNAD2"
                     /note="major polyA site"
ORIGIN      
        1 ggttacagca gcagttccag cagcagcggc ggcagccaga acaggagcag cgatagctcg
       61 ggtttccgga acaggagccg gggcagcggc ggcagctcag tgctgggcac ctgtgcggag
      121 caggagtagc aggaccacgg ggtggggtcg gcgccagcca ctctgagcca gagaaggaag
      181 gggcatctcc cagattccac tgctgggaat aatctccagg ggaggtggcg ctgaactggg
      241 aatactggtg ggggtgaaca tgtgcaggaa cagctagagg cctcggggca ggaaaacatt
      301 tggttcacgt gtaaacaggc aaggaaagct gtctgggacc atggcagcct cccgcctgga
      361 ctttggggag gtggaaactt tcctggacag gcacccagag ttgtttgaag attacttgat
      421 gcggaagggg aagcaggaga tggttgaaaa gtggctgcag aggcacagtc agggtcaggg
      481 ggctttaggt ccaaggccct ctttggctgg taccagcagc ttggctcaca gcacctgcag
      541 aggtggcagc agcgttggtg gtggcactgg accaaatggc tctgcccaca gccagcccct
      601 tcccggtggc ggggactgtg gtggggttcc cttgagtccc agctgggccg gtggcagcag
      661 gggcgatggg aacctgcagc ggagagcttc tcagaaagag ctaaggaaga gttttgcccg
      721 ctccaaggcc atccacgtga acaggaccta cgatgaacag gtgacctccc gggctcagga
      781 acccctgagt agtgtacgac ggagggcact tctccggaag gcaagctccc tgccccccac
      841 cacagcccat attctcagtg cgctgctgga atcgagagtg aatctgcctc ggtatccccc
      901 tacagccatc gactacaagt gccatctgaa aaagcataat gagcgtcagt tctttctgga
      961 attggtcaaa gatatctcca atgaccttga cctcaccagc ctgagctaca agattctcat
     1021 ctttgtctgc cttatggtgg atgctgaccg ctgctctctt ttcctggtgg aaggggcagc
     1081 tgctggcaag aagaccttgg tctccaaatt ctttgatgtg catgcaggaa cacctctgct
     1141 gccttgcagc agcacagaga actcaaatga ggtgcaggtc ccctggggca aaggtatcat
     1201 tggctatgtc ggggagcatg gagaaacggt caacattcct gatgcctacc aggatcgacg
     1261 attcaatgat gaaatcgaca agctaactgg atacaagaca aaatcattat tgtgcatgcc
     1321 tatccgaagc agtgatggtg agattattgg tgtggcccaa gcgataaata agattcctga
     1381 aggagctcca tttactgaag atgatgaaaa agttatgcag atgtatcttc cattttgtgg
     1441 aatcgccata tctaacgctc agctctttgc tgcctcaagg aaagaatatg aaagaagcag
     1501 agctttgcta gaggtggtta atgacctctt tgaagaacag actgacctgg agaaaattgt
     1561 caagaaaata atgcatcggg cccaaactct gctgaaatgt gaacgctgtt ctgttttact
     1621 cctagaggac atcgaatcac cagtggtgaa atttaccaaa tcctttgaat tgatgtcccc
     1681 aaagtgcagt gctgatgctg agaacagttt caaagaaagc atggagaaat catcatactc
     1741 cgactggcta ataaataaca gcattgctga gctggttgct tcaacaggcc ttccagtgaa
     1801 catcagtgat gcctaccagg atccgcgctt tgatgcagag gcagaccaga tatctggttt
     1861 tcacataaga tctgttcttt gtgtccctat ttggaatagc aaccaccaaa taattggagt
     1921 ggctcaagtg ttaaacagac ttgatgggaa accttttgat gatgcagatc aacgactttt
     1981 tgaggctttt gtcatctttt gtggacttgg catcaacaac acaattatgt atgatcaagt
     2041 gaagaagtcc tgggccaagc agtctgtggc tcttgatgtg ctatcatacc atgcaacatg
     2101 ttcaaaagct gaagttgaca agtttaaggc agccaacatc cctctggtgt cagaacttgc
     2161 catcgatgac attcattttg atgacttttc tctcgacgtt gatgccatga tcacagctgc
     2221 tctccggatg ttcatggagc tggggatggt acagaaattt aaaattgact atgagacact
     2281 gtgtaggtgg cttttgacag tgaggaaaaa ctatcggatg gttctatacc acaactggag
     2341 acatgccttc aacgtgtgtc agctgatgtt cgcgatgtta accactgctg ggtttcaaga
     2401 cattctgacc gaggtggaaa ttttagcggt gattgtggga tgcctgtgtc atgacctcga
     2461 ccacagggga accaacaatg ccttccaagc taagagtggc tctgccctgg cccaactcta
     2521 tggaacctct gctaccttgg agcatcacca tttcaaccac gccgtgatga tccttcaaag
     2581 tgagggtcac aatatctttg ctaacctgtc ctccaaggaa tatagtgacc ttatgcagct
     2641 tttgaagcag tcaatattgg caacagacct cacgctgtac tttgagagga gaactgaatt
     2701 ctttgaactt gtcagtaaag gagaatacga ttggaacatc aaaaaccatc gtgatatatt
     2761 tcgatcaatg ttaatgacag cctgtgacct tggagccgtg accaaaccgt gggagatctc
     2821 cagacaggtg gcagaacttg taaccagtga gttcttcgaa caaggagatc gggagagatt
     2881 agagctcaaa ctcactcctt cagcaatttt tgatcggaac cggaaggatg aactgcctcg
     2941 gttgcaactg gagtggattg atagcatctg catgcctttg tatcaggcac tggtgaaggt
     3001 caacgtgaaa ctgaagccga tgctagattc agtagctaca aacagaagta agtgggaaga
     3061 gctacaccaa aaacgactgc tggcctcaac tgcctcatcc tcccctgcca gtgttatggt
     3121 agccaaggaa gacaggaact aaacctccag gtcagctgca gctgcaaaat gactacagcc
     3181 tgaagggcca ttttcagtcc agcaatgtca tccttttgtt cttttagctc agaaagacct
     3241 aacatctcaa ggatgcactg ggaagcatgc ctgggctttc accttgaagc atggtcagca
     3301 gcagagagag caacgggaag gacaaagaaa gaggtggggc agggagcaca ccccaggacc
     3361 ctcacttttc cctaatgaac acgcatgggc tgaaatgaag gctctgggta ggggactgtt
     3421 ttggatccaa ggacctgtgg acagtcggcc tacttactct gagctgaggg aacactgaac
     3481 agtaaaagcg tcattagcgc tgcttcgttt tgtatagggc ttttctgttt gttacaagcc
     3541 aaacactgcc tgtctttgct tcctgtccct gaatgccttt ttgtgccaga ctgtcccaag
     3601 aatcctaatt tgtattccat agaggtattt tatttttaat cctagagctt cttattgatg
     3661 gatcctttag aattgcctac ctaaaaggta aactatacta tccttataaa tactgatcaa
     3721 tcccagttct ccccctaaaa atgaatacat agtaggacta tagcaaatgt gtttgatggg
     3781 taattctaga ctgggactat ggtacccttt tccagagttt taaaattcaa ccttcattac
     3841 agacaaagtt ttctcccaga aggaatggat tgatagattt tgattaaagt aagggtggaa
     3901 ggaaatctgt agctggattt accacaagtg acatctagaa actatagttc acaggacaga
     3961 gcagagccat ggagactaag cattgactac cttgagttct cctagtgagg agttctggta
     4021 taaaatttaa gattactacc agtaaccaac ttaaagcaaa ctataggggt ccctaatttt
     4081 ggatttttcc ttaagtgtaa gaaacaatgc ttcaaatgtt aagaaataac agtctgggca
     4141 aagaacgcat attctatagg aagccaggtt tacaataggt aagaataaac tgtattaagt
     4201 agatgtaatg actagaaagc tgctttgctc cctatattga gaaattgtgg acatggtatg
     4261 tgttatccaa agaacattgg gctagaagat agatttctat ccttagcttt ggcattattg
     4321 actggattga cttgaacaag tcacttaact tctacaagct tgtttcctta tttgtcaaat
     4381 tagattacac taggaaacga ttctcgaaca tgttttaacc ttacaactct ttgttcaaat
     4441 aaatctttca atgaatcccc aacatataaa acgtcaaaaa gctgaattcc tatgtgaatt
     4501 ataagcaggg tttggacatc cagagcacct acaaaccttc atctctttga ttacgtacat
     4561 gggggtccac agggactctg aagagtttga aaatccctgg cctagattaa acctgagagc
     4621 cattctagct cttaaaaaaa tctgaaattt acaaaccatt tttcttgtta ttgtttttgt
     4681 ttctttgttt gtttgttttt tgagactgag ttttcactct tgttgcccag gctggagtgc
     4741 aatggcgtga tctcggctta ctgcaacctc tgcttcctgg gttcaagcaa ttctccagcc
     4801 tcaacctcct gagaagctgg gattacaggt gcctgccacc acgcctggct aatttttgta
     4861 cttttagtag acacagggtt tcaccatgtt tgccaggctg atctcaaact cctgacctca
     4921 ggtgagccac ccacctctgc ctccgaaagt gctgggatta caggcgtgag ccaccgtacc
     4981 cggcccttgt tattgttatt aatcattatc aatcattaac tttacagata ttaaagaaat
     5041 aggggccatg ttctacatgc gacattgttt tcctggcaca cagtagacaa ttcaggaaat
     5101 gtctgaagaa ggaatgggta aaattaagat accaaaatgg aattgagggg agagcaggta
     5161 attgtagaga aaaagactct ttatggcaag aaacaaagta aaagaaatgt atagaccggg
     5221 cgcggtggct cacgcctgta atcccagcaa tttggaaggc cgaggcgggc ggatcacgag
     5281 gtcaggagat cgagaccgtc ctggctaaca cggtgaaacc ctgtctctac taaaaaacac
     5341 aaaacaaatt agccaggcgc ggtggcaggc gtctgtagtc ccagctactg gggaggctga
     5401 ggcaagagaa tggcgggaac ccgcgaggcg gagcttgcag tgagtcgaga tcacgtcact
     5461 gccctccagc ctgggcgacc agcgagactc cgtctcaaaa aaaaaaaaaa aaaaaaaaaa
     5521 aaaaaaaaaa agtataaacc agactaagag gggaataaaa gcaagaagaa aaagaaacgt
     5581 aagaacacca gtaaaggaaa gacagggacc gagacaggtg gttaagggaa atgaaaaaaa
     5641 aaaaaaaaag gtgaaagtca atccaaacaa agaaaaatgg cacttccaac caaaaaaaat
     5701 gaaggtgtag aaccctgtca tcaattgctc agaaaagaga gacacttgag cagggagggg
     5761 tttgagaaag gggagaagga aggagtgaga gccctaaaaa ataatgttcc tagctaccct
     5821 ttacagctgt ctctgcaggg aagactggag aaagtagagg gggaaatgaa tgcaggaaga
     5881 aactgcctct gcagagcagg taagaggagg ttgttcagat ttatggattt tattaagcca
     5941 gttttctgta tcactctgct ataaaggaaa atagcttctg cagggctgtc tctcctcctt
     6001 caggtgggga acaaagggtg ggtggagtca gggacagagt ctggtctgcg agatcgtgac
     6061 gtgtctgcag ctccgaagca ctgcaggtgt ttctgggtaa tgtgccacat catgtttata
     6121 tcacgaacgg gaattgaaaa tcagtctgtg tgaggcagag atgagcccac atctgttatc
     6181 ctccccaaca ataaataaat aaatagccca gacaaatgga tgccagtcca tctacagcaa
     6241 cattttaaag catgtgcttt atgacaaaac tggacccagg gtctgacaga gactgcaggc
     6301 tgccgtgagc actgtagcta tcctgaacat tgatgctaca tattgctaag gggaacataa
     6361 tttatagcat aaaccctaca agcttccact aaggttgagt tttcctctca ttttcttgcc
     6421 gttttattgg cttcactgca tggttgccaa tagcaacatc cactggtagc aaggggagtt
     6481 caacaccatt gcaatctgcc atacagtgga gccctgacaa tgtcaaccat caatctagta
     6541 gctgtttgta attgcctcca tctatttctc ctgtcttgag gtatctttcc tattgtgggt
     6601 caagatttag aaactgctga ctaatgccat gggtctgtgt ctccatgact atgaagcagt
     6661 ggacaggaag gtagcagctt cctggtgcca acaaccccag aggttagagg ttgaactctt
     6721 gcgggtttca ggcgttttta atcccttttc taaacaattt ataattttgc aagaatgtga
     6781 ggcatatgca gttatccata taatctgctt ttccaaaaaa gagaaaggaa gtttcccagt
     6841 ccttattatt aatgtttatt tcctattgga gaaagacatt tgaaatatga gccttcttgt
     6901 aaaaactcaa actgaccaga ttatgtttgc ttcctcaggt ctcttggcat taattgttga
     6961 aataacttca tcctactttt tcgatgagat gtattttttt cagacatatt tattcttact
     7021 agtcactatg tagctattat gtgcacaatc tacaatgtag tggcaatcct ggtgggtagg
     7081 gacagcttca catactgcaa agggtgccat tcagtgcata gcagactgga actccctcct
     7141 agcttggcca ccagctgaac ctgtaatctt aggactctcc aagtcttaga atctccatct
     7201 attacataaa agcactgact tttattcagt ccccacacca aaggaccaag acgtgtttag
     7261 ctttaaagaa attttccaga taattttctt ttttattctt ctcaaataaa atagcaacaa
     7321 acctaaagca gtcatcttct taataaagac ataataaaac ttacatatat ggggtagatg
     7381 taagcacaat catactacag atgtatcttg agcctgtctc taattatgat gaaagatgta
     7441 gtcatcaata caatttaaaa aaagatatgt cctttttttg agacagggtc ttgctctgtc
     7501 acccaggctg gagggcagtg gcacaatcac agccactgca gccttgacct ctccaactta
     7561 agtgatcttt cctgcctcag cctcatgagt agctgggacc acaggtgtgc accaccacac
     7621 ccagctaaat tttgtattgt ttgtaaagac gaggcctcac tatgctgacc acactggtct
     7681 cgaactcctg ggctcaagca atcctcctgc cttggcctcc caaagtgtta gggttagaga
     7741 tatgaaccac cacacccacc ttatatgtcc ttttatttca taaaaaacaa ttttagatta
     7801 tctgatatca cacatatccc ataaatggta gtcattaatt tagaagtgaa tttataaagt
     7861 taagagaagt taaaattgca catgcatttt gtttctaaaa tctgagatgt ctatgcattt
     7921 ccaggtattg tatatttgca aatacattgg gttagaaatc atctttaaca ttttgtgtta
     7981 gtgtaataac aatattatct aatattaatg ctgccagaat ccagttgctt tttctgtgta
     8041 tcaaaattta tcataacttt ttccacttaa cactaggtaa ttaaacagaa tctgcccaat
     8101 ttattctgca gtaaaattat tttaaaatct atttttcctg ctgactctta gaaattgcag
     8161 aaagacaaaa accagtttca tctccagtaa tagtgtgaaa caatttcctt ccagtgggac
     8221 agaaacctag acatactagg gaaagattta aatataaaga aaaatgcctt ggctgaaaaa
     8281 aaaaaaaacc accaaaacac aaaaaggatt cattaaagca acagaacaaa acctaatttg
     8341 ggaccctaaa aactctggca atgccactgt aatgaagttt cattatctgc ttcagagtaa
     8401 cagtctctga aattgttatt ctgctacatg ctgtaaagaa ctcccaaaac tcaaatgtat
     8461 caggaaatgt aaaggttaag tctgactaca agaaggccaa aattgcacca gcttcctaag
     8521 tgaagaataa tagaataaaa catatagagg gcagaaataa aatgaggtgt atctggagaa
     8581 tttcatgatg agcatttaga tttagcaatg cccaatgtca tgctgacact gtttgtcatg
     8641 accttgtctt cagctagtaa tttggggttg tactttttta aatttaattt tgaatgttct
     8701 tgcatgtttg gtacctctct cctcactgct aaagataaat tgtttatctg tataacataa
     8761 ctacaccaat gtcatttttg tatacgctag tacacaaatg tgttttttta ttaagtaatg
     8821 aagtatttgc tgtgaaaaat gtattatttg tgccaccgtt tatatctgtg ttcattttct
     8881 gtgtgtatat gcgtgtgtat tcgaatctca atttttcttt tactctagtt tagattaaga
     8941 catatttaga tgaaatttta aaaataacat tggaaatagg aggctaagtt ttgttgagtc
     9001 tcattccctt ggggggaaat tgcttttgcc attttatttt catgtacaat aacctaaaaa
     9061 ggatctccta ctgacttcct tcctaattat tattgtttta cacgaaagaa aggaaatacg
     9121 ttttcaattg agttgtttga aatcattcac tttgtgtaga tttcccagac tgatgtttca
     9181 ttgtaagaat attacattat agacaggttg gccatttcac aagcaactaa tccatagttt
     9241 tggaagcccg ctttaagaga cctgaatatc tttgttttta ataaaatact tagagtttaa
     9301 ctaaa
//
