Η Γενετική του Συνδρόµου Gilles de la...

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  • Gilles de la Tourette

    Gilles de la Tourette

    , PhD, DABMG

    Tourette Syndrome GeneticsThe Southern and Eastern

    Europe Initiativehttp://tsgenesee.mbg.duth.gr/

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    Tourette (GTS)

    GTS

    GTS ~10%

    ~15%

    ~12%

    ~35-40%

    10-15%

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    Tourette (GTS)

    GTS

    : 53%

    : 8%

    : 77%

    : 23%

    Price et al. Arch Gen Psychiatry 1985Hyde et al. Neurology 1992

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    GTS, CT ( ) OC ( )

    GTS

    0.3740.3680.38

    0.1150.1520.072OCB

    0.1730.1680.175CT

    0.0870.0340.15GTS

    Pauls et al. Am J Hum Genet 1991

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    Tourette

    (

    )

    GTSPauls and Leckman 1986, Pauls et al. 1991

    Eapen et al. 1993, Van de Wetering 1993Hasstedt et al. 1995, Walkup et al. 1996

    Hebebrand et al. 1997, Seuchter et al. 2000

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    (candidate gene approach)

    (positional cloning)

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    (Single Nucleotide polymorphisms - SNPs)

    ( - -

    (microsatellites STRPs)

    1

    2

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    1 1

    1 2

    1 1

    1 1

    2 2

    1 1 2 2

    2 2

    1 2

    1 12 2 1 2

    2 22 2

    2 21 2 1 2 1 2 1 1

    1 2 1 2 1 2 2 2

    2 2

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    GTS

    DRD1, DRD2, DRD3, DRD4, DRD5(Grice et al. 1996, Comings et al. 1997, Lee et al. 2005 ..)

    (DAT1)(Comings et al 1996, Faraone et al. 2005, Yoon et al. 2007 ..) (-)(Gade et al.1998, Daz-Anzalda et al. 2004 ..)

    (5HTT)(Comings et al. 2001, Cheon et al. 2004 ..) -2 (TPH2) (Mssner et al 2007) (-)(Gade et al.1998, Daz-Anzalda et al. 2004 ..)

    ADRA2A, ADRA2C(Xu et al. 2003 ..)

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    2p265 18

    TSAICG 2006

    17q254 96

    Paschou et al. 2004

    5, 10, 131 Curtis et al. 2004

    2p, 8q, 11q Simonic et al. 2001

    11q1

    Merette et al. 20004q, 8p92 TSAICG 19995, 198 Barr et al. 1999

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    17q25 GTS

    Utah (Leppert et al. 1996)

    GTS (Zhang et al. 2002)

    Zhang et al. Am J Hum Genet 2002

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    17q25 GTS

    4 ( 462 105 GTS)

    13 17 17 (17q25) 25 SNPs 17q25

    96 ( GTS )

    Paschou et al. Am J Hum Genet 2004

    17q25

    D17S928

  • Paschou et al. Am J Hum Genet 2004

    0

    500

    1000

    1500

    2000

    2500

    3000

    3500

    4000

    4500

    5000

    25 SNPs 17q25

    (Kb)

    4 GTS

    96 - GTS

    - TDT (P

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    GTS

    Taylor et al. 2001 9 Brett et al. 1996 - 3 8 Comings et al. 1996 - - 7 18 Petek et al. 2001 7q IMMP2L Crawford et al. 2003 - 6 8 State et al. 2003 18q21-q22 Verkerk et al. 2003 - 7 2 - CNTNAP2 Abelson et al. 2005 13q SLITRK1

    ,

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    SLITRK1

    Slit and Trk-like 1 (SLITRK1) GTS

    13q31.1 GTS.

    Abelson et al. Science 2005

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    SLITRK1

    174

    .

    3600 .

    Abelson et al. Science 2005

    mRNA SLITRK1 GTS. SLITRK1, .

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    SLITRK1 GTS

    1191 GTS 2382 ( )

    Abelson et al (2005)

    H 3

    Scharf et al. Neurology 2008

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    Tourette Syndrome Association International

    Consortium for Genetics

    TSAICG Am J Hum Genet 2006

    2040 265 18 ( 272 - 91 GTS CT)

    928 GTS CT311 OCD31 OCD

    390 10 cM >80%

    YGTSS, YBOCS, Conners, K-SADS-PL, SCID ()

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    TSAICG Am J Hum Genet 2006

    390 2040 (928 GTS)

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    TSAICG Am J Hum Genet 2006

    o 2p32.2

    D2S144

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    2p

    Verkerk et al. Genomics 2003

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    Tourette

    Tourette Syndrome Association, USA

    E GTS

    GTS

    GTS

    GTS

    ( / )

    (, , , , , , )

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    Tourette

    GTS

    600 (: GTS )

    : 100 () GTS

    http://utopia.duth.gr/~ppaschou/TSGeneSEE

    http://tsgenesee.mbg.duth.gr

    Tourette Syndrome Association, USA

  • Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

    Tourette

    Tourette Syndrome Association, USA

    ourette Syndrome Association International Consortium for Genetics

    GTS

    1 : 2.000 GTS ( )

    2 : 4.000 GTS

    500.000

    ( )

    http://utopia.duth.gr/~ppaschou/TSGeneSEE [email protected]://tsgenesee.mbg.duth.gr

  • Tourette Syndrome Association, USA

    /

    Kenneth K. KiddJudith KiddAndrew PakstisJames LeckmanRobert KingYale University

    David PaulsHarvard University

    TSGeneSEE - http://tsgenesee.mbg.duth.gr/

    Csaba Barta, Julia Gadoros, VadaskertTomasz Wolanczyk, Warsaw UniversityRenata Rizzo, University of Catania

    Anatoly Severny, Moscow Res. Institute of PsychiatryVsevolod Rozanov, Odessa UniversityMira Kapisyzi, University Hospital Centre Mother Theresa