Haplotype evolution of SLITRK1, a candidate gene for Gilles de la Tourette syndrome.
Gilles de la Tourette syndrome (GTS) is a complex disorder with a clear genetic component but no clearly identified genes with variation of etiologic relevance. Various candidate regions and genes show some evidence of affecting risk, though clearly not all patients/families can be explained by any one of them. Resequencing one candidate gene, SLITRK1, has identified four new variants. Including them, we have typed over 2,300 normal individuals from 44 populations for 11 SNPs spanning the gene. The unusual global pattern seen is that one non-ancestral haplotype is the single most common haplotype worldwide. Other haplotypes appear to result from accumulation of mutations with no evidence of historical recombination. Although there is no evidence of selection, the haplotype frequency variation seen around the world will need to be considered in any future association studies of this locus with GTS or any other neuropsychiatric disorder.
Speed
William C
WC
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA.
O'Roak
Brian J
BJ
Tárnok
Zsanett
Z
Barta
Csaba
C
Pakstis
Andrew J
AJ
State
Matthew W
MW
Kidd
Kenneth K
KK
D004252:DNA Mutational Analysis; D019143:Evolution, Molecular; D006239:Haplotypes; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D017720:Molecular Epidemiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D005879:Tourette Syndrome / Q000453:epidemiology / Q000235:genetics*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C505093:SLITRK1 protein, human