With the continuing support of the TSA, the Dutch Tourette Family Study Research Group will be able to proceed with its contributions to the efforts of the GTS Gene Mapping Consortium. In the next year the collaboration within this Consortium will be further intensified, much inspired by the discussions with and the suggestions of the genetic scientists from the Scientific Advisory Board of the TSA. As was discussed at length at the latest Genetic Workshop in Boston, a protocol will be designed that will allow for more refined diagnostic classification of affected persons in the studied families. All clinicians will participate in this part of the project. In the forthcoming year, the Dutch families will be investigated again to update the clinical information and to apply the new diagnostic approach. In collaboration with David Pauls from the Yale Child Study Center, segregation analyses will be carried out on the collaborative family data using the latest diagnostic information. The results of the first analyses turned out to be consistently in agreement with the results reported in the earlier studies of the Yale group. Peter Heutink of Rotterdam will continue to summarize the linkage data on the polymorphic DNA markers in close collaboration with Andrew Pakstis from Kenneth Kidd’s lab at Yale into a comprehensive exclusion map. Peter Heutink (who successfully mapped a tumor gene at Marshfield Clinic utilizing Dr. Weber’s microsatellite DNA polymorphisms) will proceed with the analysis of the latest GTS data. In cooperation with the genetic statistician Lodewijk Sandkuijl M.D., simulation studies will be performed using new statistical approaches to obtain more insight into the complex genetic models relevant to the heredity of GTS. The simulation studies already have shown the power for linkage of the available pedigrees under different genetic models. The most informative and thus promising families, according to these analyses, will be included consistently in each analysis of each group at each lab. The strong sense of collaboration within the Consortium has proved to be fundamental for the continuation of the developments over the past year. B.J.M. van de Wetering, M.D. University Hospital Rotterdam, The Netherlands Award $40,000 Tourette Association of America Inc. – Research Grant Award 1992