IDENTIFICATION OF GENETIC-MARKERS ASSOCIATED WITH GILLES-DE-LA-TOURETTE-SYNDROME IN AN AFRIKANER POPULATION

Because gene-mapping efforts, using large kindreds and parametric meth ods of analysis, for the neurologic disorder Tourette syndrome have fa iled, efforts are being redirected toward association studies in young , genetically isolated populations. The availability of dense marker m aps makes it feasible to search for association throughout the entire genome. We report the results of such a genome scan using DNA samples from Tourette patients and unaffected control subjects from the South African Afrikaner population. To optimize mapping efficiency, we chose a two-step strategy. First, we screened pools of DNA samples from bot h affected and control individuals, using a dense collection of 1,167 short tandem-repeat polymorphisms distributed throughout the genome. S econd, we typed those markers displaying evidence of allele frequency- distribution shifts, along with additional tightly linked markers, usi ng DNA from each affected and unaffected individual. To reduce false p ositives, we tested two independent groups of case and control subject s. Strongest evidence for association (P values 10(-2) to 10(-5)) were obtained for markers within chromosomal regions encompassing D2S1790 near the chromosome 2 centromere, D6S477 on distal 6p, D8S257 on 8q, D 11S933 on 11q, D14S1003 on proximal 14q, D20S1085 on distal 20q, and D 21S1252 on 21q.