LOCUS       NM_000161.2             2941 bp    mRNA    linear   PRI 20-AUG-2006
DEFINITION  Homo sapiens GTP cyclohydrolase 1 (dopa-responsive dystonia)
            (GCH1), transcript variant 1, mRNA.
ACCESSION   NM_000161 GI:66932966 LOCUS:NM_000161 GB:NM_000161 SeqStore:3612084154.5
VERSION     NM_000161.2
KEYWORDS    .
SOURCE      human
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1
  AUTHORS   Swick,L.; Kapatos,G.
  TITLE     A yeast 2-hybrid analysis of human GTP cyclohydrolase I protein
            interactions
  JOURNAL   J. Neurochem. 97 (5), 1447-1455 (2006)
  REMARK    GeneRIF: Aha1 may recruit GCH1 into the endothelial nitric oxide
            synthase/heat shock protein (eNOS/Hsp90) complex to support
            changes in endothelial nitric oxide production through the local
            synthesis of BH4.
   PUBMED   16696853
REFERENCE   2
  AUTHORS   Al Sarraj,J.; Vinson,C.; Han,J.; Thiel,G.
  TITLE     Regulation of GTP cyclohydrolase I gene transcription by basic
            region leucine zipper transcription factors
  JOURNAL   J. Cell. Biochem. 96 (5), 1003-1020 (2005)
  REMARK    GeneRIF: GTP cyclohydrolase I gene transcription is regulated by
            basic region leucine zipper transcription factors
   PUBMED   16149046
REFERENCE   3
  AUTHORS   Ohta,E.; Toyoshima,I.; Funayama,M.; Ichinose,H.; Hasegawa,K.;
            Obata,F.
  TITLE     A new mutation (Thr106Ile) of the GTP cyclohydrolase 1 gene
            associated with DYT5 dystonia (Segawa disease)
  JOURNAL   Mov. Disord. 20 (8), 1083-1084 (2005)
  REMARK    GeneRIF: A new mutation (Thr106Ile) of the GTP cyclohydrolase 1
            gene associated with DYT5 dystonia (Segawa disease).
   PUBMED   15852365
REFERENCE   4
  AUTHORS   Kealey,C.; Roche,S.; Claffey,E.; McKeon,P.
  TITLE     Linkage and candidate gene analysis of 14q22-24 in bipolar
            disorder: support for GCHI as a novel susceptibility gene
  JOURNAL   Am. J. Med. Genet. B Neuropsychiatr. Genet. 136 (1), 75-80 (2005)
  REMARK    GeneRIF: Results suggest that variants within GCHI may contribute
            to bipolar disorder in the Irish population.
   PUBMED   15909293
REFERENCE   5
  AUTHORS   Hagenah,J.; Saunders-Pullman,R.; Hedrich,K.; Kabakci,K.;
            Habermann,K.; Wiegers,K.; Mohrmann,K.; Lohnau,T.; Raymond,D.;
            Vieregge,P.; Nygaard,T.; Ozelius,L.J.; Bressman,S.B.; Klein,C.
  TITLE     High mutation rate in dopa-responsive dystonia: detection with
            comprehensive GCHI screening
  JOURNAL   Neurology 64 (5), 908-911 (2005)
  REMARK    GeneRIF: We tested 23 individuals with dopamine-resistant dystonia
            for the different GCH1 mutation types by conventional and
            quantitative PCR analyses and found mutations, including two large
            exon deletions, in 87%.
   PUBMED   15753436
REFERENCE   6
  AUTHORS   Huang,A.; Zhang,Y.Y.; Chen,K.; Hatakeyama,K.; Keaney,J.F. Jr.
  TITLE     Cytokine-stimulated GTP cyclohydrolase I expression in endothelial
            cells requires coordinated activation of nuclear factor-kappaB and
            Stat1/Stat3
  JOURNAL   Circ. Res. 96 (2), 164-171 (2005)
  REMARK    GeneRIF: GTPCH1 induction in endothelial cells is stimulated by
            cytokines and mediated by Stat1/3, Jak2 and NF-kappaB.
   PUBMED   15604419
REFERENCE   7
  AUTHORS   Hynes,S.O.; Smith,L.A.; Richardson,D.M.; Kovesdi,I.; O'Brien,T.;
            Katusic,Z.S.
  TITLE     In vivo expression and function of recombinant GTPCH I in the
            rabbit carotid artery
  JOURNAL   Am. J. Physiol. Heart Circ. Physiol. 286 (2), H570-H574 (2004)
  REMARK    GeneRIF: Genetic transfer into rabbit vascular endothelium in vivo
            increases intracellular concentration of tetrahydrobiopterin.
   PUBMED   14551046
REFERENCE   8
  AUTHORS   Garavaglia,B.; Invernizzi,F.; Carbone,M.L.; Viscardi,V.;
            Saracino,F.; Ghezzi,D.; Zeviani,M.; Zorzi,G.; Nardocci,N.
  TITLE     GTP-cyclohydrolase I gene mutations in patients with autosomal
            dominant and recessive GTP-CH1 deficiency: identification and
            functional characterization of four novel mutations
  JOURNAL   J. Inherit. Metab. Dis. 27 (4), 455-463 (2004)
   PUBMED   15303002
REFERENCE   9
  AUTHORS   Zheng,J.S.; Yang,X.Q.; Lookingland,K.J.; Fink,G.D.; Hesslinger,C.;
            Kapatos,G.; Kovesdi,I.; Chen,A.F.
  TITLE     Gene transfer of human guanosine 5'-triphosphate cyclohydrolase I
            restores vascular tetrahydrobiopterin level and endothelial
            function in low renin hypertension
  JOURNAL   Circulation 108 (10), 1238-1245 (2003)
  REMARK    GeneRIF: Gene transfer of human GTPCH I restored arterial GTPCH I
            activity and BH4 levels, resulting in reduced O2- and improved
            endothelium-dependent relaxation and basal NO release in DOCA-salt
            hypertensive rats
   PUBMED   12925450
REFERENCE   10
  AUTHORS   Hwu,W.L.; Yeh,H.Y.; Fang,S.W.; Chiang,H.S.; Chiou,Y.W.; Lee,Y.M.
  TITLE     Regulation of GTP cyclohydrolase I by alternative splicing in
            mononuclear cells
  JOURNAL   Biochem. Biophys. Res. Commun. 306 (4), 937-942 (2003)
  REMARK    GeneRIF: GTP cyclohydrolase I is alternatively spliced in
            mononuclear cells
   PUBMED   12821132
REFERENCE   11
  AUTHORS   Leuzzi,V.; Carducci,C.; Carducci,C.; Cardona,F.; Artiola,C.;
            Antonozzi,I.
  TITLE     Autosomal dominant GTP-CH deficiency presenting as a
            dopa-responsive myoclonus-dystonia syndrome
  JOURNAL   Neurology 59 (8), 1241-1243 (2002)
  REMARK    GeneRIF: A kindred is reported in which GTP-CH deficiency presents
            as a dopa-responsive myoclonus-dystonia syndrome, documented as a
            missense mutation in exon 6 of GTP-CH1 gene (K224R).
   PUBMED   12391354
REFERENCE   12
  AUTHORS   Muller,U.; Steinberger,D.; Topka,H.
  TITLE     Mutations of GCH1 in Dopa-responsive dystonia
  JOURNAL   J. Neural Transm. 109 (3), 321-328 (2002)
  REMARK    Review article
   PUBMED   11956954
REFERENCE   13
  AUTHORS   Dhondt,J.L.; Hayte,J.M.
  TITLE     [Screening of tetrahydrobiopterin deficiency among
            hyperphenylalaninemic patients]
  JOURNAL   Ann. Biol. Clin. (Paris) 60 (2), 165-171 (2002)
   PUBMED   11937441
REFERENCE   14
  AUTHORS   Bader,G.; Schiffmann,S.; Herrmann,A.; Fischer,M.; Gutlich,M.;
            Auerbach,G.; Ploom,T.; Bacher,A.; Huber,R.; Lemm,T.
  TITLE     Crystal structure of rat GTP cyclohydrolase I feedback regulatory
            protein, GFRP
  JOURNAL   J. Mol. Biol. 312 (5), 1051-1057 (2001)
  REMARK    GeneRIF: kinetic studies with GFRP
   PUBMED   11580249
REFERENCE   15
  AUTHORS   Skrygan,M.; Bartholome,B.; Bonafe,L.; Blau,N.; Bartholome,K.
  TITLE     A splice mutation in the GTP cyclohydrolase I gene causes
            dopa-responsive dystonia by exon skipping
  JOURNAL   J. Inherit. Metab. Dis. 24 (3), 345-351 (2001)
   PUBMED   11486899
REFERENCE   16
  AUTHORS   Golderer,G.; Werner,E.R.; Heufler,C.; Strohmaier,W.; Grobner,P.;
            Werner-Felmayer,G.
  TITLE     GTP cyclohydrolase I mRNA: novel splice variants in the slime
            mould Physarum polycephalum and in human monocytes (THP-1)
            indicate conservation of mRNA processing
  JOURNAL   Biochem. J. 355 (PT 2), 499-507 (2001)
   PUBMED   11284739
REFERENCE   17
  AUTHORS   Hong,K.M.; Kim,Y.S.; Paik,M.K.
  TITLE     A novel nonsense mutation of the GTP cyclohydrolase I gene in a
            family with dopa-responsive dystonia
  JOURNAL   Hum. Hered. 52 (1), 59-60 (2001)
   PUBMED   11359069
REFERENCE   18
  AUTHORS   Auerbach,G.; Herrmann,A.; Bracher,A.; Bader,G.; Gutlich,M.;
            Fischer,M.; Neukamm,M.; Garrido-Franco,M.; Richardson,J.; Nar,H.;
            Huber,R.; Bacher,A.
  TITLE     Zinc plays a key role in human and bacterial GTP cyclohydrolase I
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 97 (25), 13567-13572 (2000)
   PUBMED   11087827
REFERENCE   19
  AUTHORS   Hwu,W.L.; Wang,P.J.; Hsiao,K.J.; Wang,T.R.; Chiou,Y.W.; Lee,Y.M.
  TITLE     Dopa-responsive dystonia induced by a recessive GTP cyclohydrolase
            I mutation
  JOURNAL   Hum. Genet. 105 (3), 226-230 (1999)
   PUBMED   10987649
REFERENCE   20
  AUTHORS   Steinberger,D.; Topka,H.; Fischer,D.; Muller,U.
  TITLE     GCH1 mutation in a patient with adult-onset oromandibular dystonia
  JOURNAL   Neurology 52 (4), 877-879 (1999)
   PUBMED   10078749
REFERENCE   21
  AUTHORS   Brique,S.; Destee,A.; Lambert,J.C.; Mouroux,V.; Delacourte,A.;
            Amouyel,P.; Chartier-Harlin,M.C.
  TITLE     A new GTP-cyclohydrolase I mutation in an unusual dopa-responsive
            dystonia, familial form
  JOURNAL   Neuroreport 10 (3), 487-491 (1999)
   PUBMED   10208576
REFERENCE   22
  AUTHORS   Furukawa,Y.; Kish,S.J.; Bebin,E.M.; Jacobson,R.D.; Fryburg,J.S.;
            Wilson,W.G.; Shimadzu,M.; Hyland,K.; Trugman,J.M.
  TITLE     Dystonia with motor delay in compound heterozygotes for
            GTP-cyclohydrolase I gene mutations
  JOURNAL   Ann. Neurol. 44 (1), 10-16 (1998)
   PUBMED   9667588
REFERENCE   23
  AUTHORS   Tamaru,Y.; Hirano,M.; Ito,H.; Kawamura,J.; Matsumoto,S.; Imai,T.;
            Ueno,S.
  TITLE     Clinical similarities of hereditary progressive/dopa responsive
            dystonia caused by different types of mutations in the GTP
            cyclohydrolase I gene
  JOURNAL   J. Neurol. Neurosurg. Psychiatr. 64 (4), 469-473 (1998)
   PUBMED   9576537
REFERENCE   24
  AUTHORS   Katusic,Z.S.; Stelter,A.; Milstien,S.
  TITLE     Cytokines stimulate GTP cyclohydrolase I gene expression in
            cultured human umbilical vein endothelial cells
  JOURNAL   Arterioscler. Thromb. Vasc. Biol. 18 (1), 27-32 (1998)
   PUBMED   9445252
REFERENCE   25
  AUTHORS   Weber,Y.; Steinberger,D.; Deuschl,G.; Benecke,R.; Muller,U.
  TITLE     Two previously unrecognized splicing mutations of GCH1 in
            Dopa-responsive dystonia: exon skipping and one base insertion
  JOURNAL   Neurogenetics 1 (2), 125-127 (1997)
   PUBMED   10732814
REFERENCE   26
  AUTHORS   Thony,B.; Blau,N.
  TITLE     Mutations in the GTP cyclohydrolase I and
            6-pyruvoyl-tetrahydropterin synthase genes
  JOURNAL   Hum. Mutat. 10 (1), 11-20 (1997)
  REMARK    Review article
   PUBMED   9222755
REFERENCE   27
  AUTHORS   Ichinose,H.; Ohye,T.; Matsuda,Y.; Hori,T.; Blau,N.; Burlina,A.;
            Rouse,B.; Matalon,R.; Fujita,K.; Nagatsu,T.
  TITLE     Characterization of mouse and human GTP cyclohydrolase I genes.
            Mutations in patients with GTP cyclohydrolase I deficiency
  JOURNAL   J. Biol. Chem. 270 (17), 10062-10071 (1995)
   PUBMED   7730309
REFERENCE   28
  AUTHORS   Nomura,T.; Ohtsuki,M.; Matsui,S.; Sumi-Ichinose,C.; Nomura,H.;
            Hagino,Y.; Iwase,K.; Ichinose,H.; Fujita,K.; Nagatsu,T.
  TITLE     Isolation of a full-length cDNA clone for human GTP cyclohydrolase
            I type 1 from pheochromocytoma
  JOURNAL   J. Neural Transm. Gen. Sect. 101 (1-3), 237-242 (1995)
   PUBMED   8695054
REFERENCE   29
  AUTHORS   Imazumi,K.; Sasaki,T.; Takahashi,K.; Takai,Y.
  TITLE     Identification of a rabphilin-3A-interacting protein as GTP
            cyclohydrolase I in PC12 cells
  JOURNAL   Biochem. Biophys. Res. Commun. 205 (2), 1409-1416 (1994)
   PUBMED   7802677
REFERENCE   30
  AUTHORS   Ichinose,H.; Ohye,T.; Takahashi,E.; Seki,N.; Hori,T.; Segawa,M.;
            Nomura,Y.; Endo,K.; Tanaka,H.; Tsuji,S. et al.
  TITLE     Hereditary progressive dystonia with marked diurnal fluctuation
            caused by mutations in the GTP cyclohydrolase I gene
  JOURNAL   Nat. Genet. 8 (3), 236-242 (1994)
   PUBMED   7874165
REFERENCE   31
  AUTHORS   Gutlich,M.; Jaeger,E.; Rucknagel,K.P.; Werner,T.; Rodl,W.;
            Ziegler,I.; Bacher,A.
  TITLE     Human GTP cyclohydrolase I: only one out of three cDNA isoforms
            gives rise to the active enzyme
  JOURNAL   Biochem. J. 302 (PT 1), 215-221 (1994)
   PUBMED   8068008
REFERENCE   32
  AUTHORS   Nygaard,T.G.; Wilhelmsen,K.C.; Risch,N.J.; Brown,D.L.;
            Trugman,J.M.; Gilliam,T.C.; Fahn,S.; Weeks,D.E.
  TITLE     Linkage mapping of dopa-responsive dystonia (DRD) to chromosome
            14q
  JOURNAL   Nat. Genet. 5 (4), 386-391 (1993)
   PUBMED   8298648
REFERENCE   33
  AUTHORS   Gutlich,M.; Schott,K.; Werner,T.; Bacher,A.; Ziegler,I.
  TITLE     Species and tissue specificity of mammalian GTP cyclohydrolase I
            messenger RNA
  JOURNAL   Biochim. Biophys. Acta 1171 (2), 133-140 (1992)
   PUBMED   1482676
REFERENCE   34
  AUTHORS   Togari,A.; Ichinose,H.; Matsumoto,S.; Fujita,K.; Nagatsu,T.
  TITLE     Multiple mRNA forms of human GTP cyclohydrolase I
  JOURNAL   Biochem. Biophys. Res. Commun. 187 (1), 359-365 (1992)
   PUBMED   1520321
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from CR589979.1, U19523.1, U66097.1
            and BM971258.1. On Jun 3, 2005 this sequence version replaced
            gi:4503948. Summary: This gene encodes a member of the GTP
            cyclohydrolase family. The encoded protein is the first and
            rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis,
            catalyzing the conversion of GTP into 7,8-dihydroneopterin
            triphosphate. BH4 is an essential cofactor required by aromatic
            amino acid hydroxylases as well as nitric oxide synthases.
            Mutations in this gene are associated with malignant
            hyperphenylalaninemia and dopa-responsive dystonia. Several
            alternatively spliced transcript variants encoding different
            isoforms have been described; however, not all variants give rise
            to a functional enzyme. Transcript Variant: This variant (1), also
            known as Type I, represents the longest transcript. Variants 1 and
            2 encode the longest isoform (1), which is the active enzyme.
            COMPLETENESS: complete on the 3' end.
FEATURES             Location/Qualifiers
     source          1..2941
                     /mol_type="mRNA"
                     /map="14q22.1-q22.2"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /organism="Homo sapiens"
     gene            1..2941
                     /db_xref="GeneID:2643"
                     /db_xref="HGNC:4193"
                     /db_xref="HPRD:HPRD_02573"
                     /db_xref="MIM:600225"
                     /gene="GCH1"
                     /note="synonyms: GCH, DYT5, GTPCH1, GTP-CH-1"
     CDS             162..914
                     /go_function="hydrolase activity [goid 0016787] [evidence
                      IEA]"
                     /go_function="protein binding [goid 0005515] [evidence
                     IPI] [pmid 16696853]"
                     /go_function="GTP cyclohydrolase I activity [goid
                     0003934]  [evidence TAS] [pmid 8702680]"
                     /protein_id="NP_000152.1"
                     /gene="GCH1"
                     /go_process="L-phenylalanine catabolism [goid 0006559]
                     [evidence IEA]"
                     /go_process="nitric oxide biosynthesis [goid 0006809]
                     [evidence TAS] [pmid 8702680]"
                     /go_process="aromatic compound biosynthesis [goid
                     0019438]  [evidence IEA]"
                     /go_process="neurotransmitter metabolism [goid 0042133]
                     [evidence TAS] [pmid 8702680]"
                     /go_process="tetrahydrobiopterin biosynthesis [goid
                     0006729] [evidence IEA]"
                     /note="isoform 1 is encoded by transcript variant 1;
                     guanosine 5'-triphosphate cyclohydrolase I"
                     /db_xref="GI:4503949"
                     /db_xref="CCDS:CCDS9720.1"
                     /db_xref="GeneID:2643"
                     /db_xref="HGNC:4193"
                     /db_xref="HPRD:HPRD_02573"
                     /db_xref="MIM:600225"
                     /codon_start=1
                     /go_component="cytoplasm [goid 0005737] [evidence IEA]"
                     /product="GTP cyclohydrolase 1 isoform 1"
                     /translation="MEKGPVRAPAEKPRGARCSNGFPERDPPRPGPSRPAEKPPRPEA
                     KSAQPADGWKGERPRSEEDNELNLPNLAAAYSSILSSLGENPQRQGLLKTPWRAASAM
                     QFFTKGYQETISDVLNDAIFDEDHDEMVIVKDIDMFSMCEHHLVPFVGKVHIGYLPNK
                     QVLGLSKLARIVEIYSRRLQVQERLTKQIAVAITEALRPAGVGVVVEATHMCMVMRGV
                     QKMNSKTVTSTMLGVFREDPKTREEFLTLIRS"
                     /EC_number="3.5.4.16"
     misc_feature    408..911
                     /db_xref="CDD:29763"
                     /gene="GCH1"
                     /note="GTP cyclohydrolase I (GTP-CH-I) catalyzes the
                     conversion of GTP into dihydroneopterin triphosphate;
                     Region: GTP_cyclohydro1; cd00642"
     STS             944..1281
                     /db_xref="UniSTS:34488"
                     /gene="GCH1"
                     /standard_name="D14S1260"
     variation       1157
                     /db_xref="dbSNP:841"
                     /replace="c"
                     /replace="t"
                     /gene="GCH1"
     variation       complement(1591)
                     /db_xref="dbSNP:10136966"
                     /replace="a"
                     /replace="g"
                     /gene="GCH1"
     variation       complement(1797)
                     /db_xref="dbSNP:34156666"
                     /replace=""
                     /replace="ttc"
                     /gene="GCH1"
     variation       complement(1799)
                     /db_xref="dbSNP:34808879"
                     /replace=""
                     /replace="ctt"
                     /gene="GCH1"
     STS             1903..2036
                     /db_xref="UniSTS:33272"
                     /gene="GCH1"
                     /standard_name="D14S1190"
     variation       complement(2056)
                     /db_xref="dbSNP:10151500"
                     /replace="a"
                     /replace="g"
                     /gene="GCH1"
     polyA_signal    2896..2901
                     /gene="GCH1"
     polyA_site      2915
                     /gene="GCH1"
     polyA_site      2926
                     /gene="GCH1"
BASE COUNT      773 a    597 c    658 g    913 t
ORIGIN      
        1 cctgtggccg ctcccggctc ggagtgtgat ctaagcaggt tgcgtacctt cctcaggtga
       61 ctccggccac agcccattgt ccgcggccac cggcggagtt tagccgcaga cctcgaagcg
      121 ccccggggtc cttcccgaac ggcagcggct gcggcgggtc catggagaag ggccctgtgc
      181 gggcaccggc ggagaagccg cggggcgcca ggtgcagcaa tgggttcccc gagcgggatc
      241 cgccgcggcc cgggcccagc aggccggcgg agaagccccc gcggcccgag gccaagagcg
      301 cgcagcccgc ggacggctgg aagggcgagc ggccccgcag cgaggaggat aacgagctga
      361 acctccctaa cctggcagcc gcctactcgt ccatcctgag ctcgctgggc gagaaccccc
      421 agcggcaagg gctgctcaag acgccctgga gggcggcctc ggccatgcag ttcttcacca
      481 agggctacca ggagaccatc tcagatgtcc taaacgatgc tatatttgat gaagatcatg
      541 atgagatggt gattgtgaag gacatagaca tgttttccat gtgtgagcat cacttggttc
      601 catttgttgg aaaggtccat attggttatc ttcctaacaa gcaagtcctt ggcctcagca
      661 aacttgcgag gattgtagaa atctatagta gaagactaca agttcaggag cgccttacaa
      721 aacaaattgc tgtagcaatc acggaagcct tgcggcctgc tggagtcggg gtagtggttg
      781 aagcaacaca catgtgtatg gtaatgcgag gtgtacagaa aatgaacagc aaaactgtga
      841 ccagcacaat gttgggtgtg ttccgggagg atccaaagac tcgggaagag ttcctgactc
      901 tcattaggag ctgagcttca ttcagtgtgt gtgcgttggt tgccgatcgt actgccagta
      961 gcattgtctg tctgtccggt cttgtttgta cattccattt tcaattgtta cagatgtgaa
     1021 ctttattcct tgtcactaat tatatttaaa attatttcta ggaagtcaaa taaatataat
     1081 aaagggttga gccctctact ttcttcttgc cacctttttg tggcaatatt aaagtgaact
     1141 gctaatagtg taagtacgtg cacaaaacca ctgccagata accagagggg cctgggaagg
     1201 gagaagaatt agtgtatttt tttcaaatag tacagtaatt tgcctcataa gcataggagc
     1261 attgggaatg agagggaact gtgcccagta tactgttttt tttcttcctc caataaaagt
     1321 ggtgtagtgc cgaaagtgct aaaatattta gtgcggtatt gctctgtgaa ttcaagttca
     1381 acagacttca ctttggtcat gtttattaaa ccaccagtga catttaaaaa tatattttta
     1441 gcagtcgtaa tgttagtcac caagggaagg tggtggaatg tctatgtttt tgattttact
     1501 gtgagttaaa aaggcacatt tctaccttct attgttttta aattcaagaa tagggaatta
     1561 gttcctggtg ttgtttacga gtgtattctc gtgtcaacat acagggattt agacatttaa
     1621 ctctctgtgc cttgataaga atatcattta gagtgtagat acttttgcct ttttaaaaaa
     1681 gccattattt tatgagactt agtactcaca ctgcaaataa ctagtcagct cagttttaac
     1741 tttataggtt tattgagttt cctttgtgtg atccatgtag atgcctcaaa atgtttcttc
     1801 ttcttctttt ttttaatctt ataagatatt tttctaagta tttccagaaa catttgagag
     1861 tgcccatcat tttcaggtct gcagaaccat agcttccacg cacctgaacg agcacagaat
     1921 gaactgacgg tggaagacat tatgagctgt gtccaacgtt ttaaccaaag cgtatcgtac
     1981 caacgatctg tgaaaatgca ctggaagctt ctggtcccgg tttcctttgt ggtctatgtg
     2041 ggtcttgtcc tcattgtaac tccgtataga tggtataggt attttaatcc tggaagctgt
     2101 tgccttatta atgattatct taaaatttcc tccattgggg cagcgtgggc caaattaaaa
     2161 caaacaaaac cgcaactcct ccacagaaac acaaacacag ttattccatg aagtttagta
     2221 tttggttgac atagtgctct tcaaattcat cccattaccc taaaagtaat aactttgatg
     2281 cttgctttaa ctttagtccc atctctgcca ctttgatgct atttgggtta tgatggggca
     2341 agatggcaga ggtattgggt ttttttgttt ttttccattc ctctctactt ctgtttccta
     2401 gctttttctt tctggagttt aagtacagtg atggttggct tgagtacctt tttaaatcta
     2461 gcccagtata aacattagcc tgcttaatat ttagacattt ataggtagaa ttctgagcac
     2521 tcaactcatg tttggcattt taaagtaaaa acaagtgtga cttcgaggac caaagaaatt
     2581 gtcagctata catttatctt tatgaactca tttatattcc tttttaatga ctcgttgttc
     2641 taacatttcc tagaagtgtt cttataaagg tctaatgtat ccacaggctg ttgtcttatt
     2701 agtaaatgca aagtaatgac tttgtctgtt ttactctagt ctttagtact tcaaaattac
     2761 cttttcatat ccatgatctt gagtccattt gggggatttt taagaatttg atgtatttca
     2821 atacactgtt caaaattaaa ttgtttaatt ttatgtatga gtatgtatgt tcctgaagtt
     2881 ggtcctattt aaattattaa actattgtaa ctttgttctt gtgaaaaaaa aaaaaaaaaa
     2941 a
//
