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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