Identification of Genetic Markers Associated with Gilles de la Tourette Syndrome in an Afrikaner Population

American Journal of Human Genetics , 63(3), 839-846 (1998)

Ingrid Simonic1, George S. Gericke1, Jurg Ott2, James L. Weber3

1MRC Neurogenetics Research Laboratory, Arcadia, South Africa;
2Rockefeller University, New York; and
3Center for Medical Genetics, Marshfield Medical Research Foundation, Marshfield, Wisconsin

Abstract

Because gene-mapping efforts, using large kindreds and parametric methods of analysis, for the neurologic disorder Tourette syndrome have failed, efforts are being redirected toward association studies in young, genetically isolated populations. The availability of dense marker maps 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 both affected and control individuals, using a dense collection of 1,167 short tandem-repeat polymorphisms distributed throughout the genome. Second, we typed those markers displaying evidence of allele frequencydistribution shifts, along with additional tightly linked markers, using DNA from each affected and unaffected individual. To reduce false positives, we tested two independent groups of case and control subjects. 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, D11S933 on 11q, D14S1003 on proximal 14q, D20S1085 on distal 20q, and D21S1252 on 21q.