Although non-genetic factors almost certainly affect the course of symptoms, Tourette Syndrome (TS) is primarily a heritable disorder. Finding the genes which cause Tourette Syndrome will provide a much deeper understanding of the condition and will ultimately lead to improved diagnosis, treatment, and perhaps even prevention. At one time researchers felt that the genetics of Tourette Syndrome were relatively straightforward, but the situation has turned out to be much more complicated. To try to reduce this complexity, we are turning to an isolated human population, namely the Afrikaners of South Africa. Afrikaners arose from a small number of Europeans who began settling in Cape Town in 1652. Because the Afrikaner population has grown rapidly from relatively few founders, it is genetically more homogeneous than populations of North America or Europe. We expect that in Afrikaner patients with TS there will be fewer TS genes and fewer variants of those genes. We previously collected DNA and phenotypic information from 100 TS affected Afrikaners and from an equal number of matched, unaffected controls. Using these DNA samples and by testing over 1,000 polymorphic DNA markers, we were able to identify 7 putative chromosomal regions containing TS genes. In this study, we will extend this earlier work by collecting DNA from the parents of the original 100 affected subjects and by collecting DNA from at least 50 additional Afrikaner families, consisting of both parents and a clearly affected child who belong to the further isolated South African Gereformeerde Church. These DNA samples will be used to type dense sets of polymorphic DNA markers within selected candidate regions with the aim of identifying common, overlapping chromosome segments shared among the affected individuals. Hopefully, these shared chromosomal regions will allow us to zoom in on the location of TS genes. Subject recruitment in Africa will be led by George Gericke, M.D. of the Medical Research Council of South Africa. He will be assisted by Dr. Marie Torrington who is an expert on Afrikaner genealogy and by Ingrid Simonic, a South African genetics Ph.D. student. Ms. Simonic will carry out the marker analysis in Dr. Weber’s laboratory at Marshfield, WI. Professor Jurg Ott at Rockefeller University in New York, will complete the statistical analyses of the resulting data. James L. Weber, Ph.D. Marshfield Medical Research Foundation Marshfield, WI Award: $33,460 Tourette Association of America Inc. – Research Grant Award 1998