Tourette Syndrome (TS) is a neuropsychiatric disorder with a strong genetic component and major gene effects. Recent genome screens of familial and sporadic TS cases have identified a number of candidate regions potentially harboring TS-susceptibility genes. In order to confirm these findings and to facilitate the identification of the specific gene mutations underlying TS, analyses in independent well-characterized study samples are now required. The general aim of this proposal is to follow-up candidate TS regions suggested by other studies and to fine-map the location of disease-susceptibility genes. We will recruit a large sample of at least 200 TS patients (and available parents) from the genetically isolated population of Antioquia (Colombia). Patients will be characterized with state-of-the-art diagnostic methods (developed by the Tourette Syndrome Association International Consortium for Genetics). Follow-up will involve high-density microsatellite genotyping of candidate regions and association testing using family and unrelated controls. For fine-mapping we will saturate regions of interest with a combination of STR and SNP polymorphisms and apply haplotype-based analyses. A distinct feature of this project is that Antioquia has a close genetic affinity with the population of the Costa Rican Central Valley, where our collaborator Dr. Nelson Freimer is conducting extensive linkage disequilibrium mapping studies of TS. The clinical characterization of patients in Antioquia and Costa Rica will use a similar approach and we will utilize a coordinated strategy for followup and fine-mapping in both study samples. The parallel genetic analysis of TS in these 2 closely related population isolates will substantially increase the power of the genetic analyses and facilitate the identification of TS genes.
