The major goal of the proposed project is to identify the gene (or genes) predisposing to schizophrenia in the geographically isolated population of Palau, Micronesia. Four large extended pedigrees containing 22, 16, 20, and 20 ascertained cases of schizophrenia will be genotyped with the latest, high density Cooperative Human Linkage Center (CHLC) genome-wide screening set of DNA markers. Linkage analyses will be subjected to linkage disequilibrium analyses using all available pedigrees, including simplex families. Candidate genes mapping to a region of linkage or linkage disequilibrium may be analyzed using mutation scanning techniques. The applicant claims that identification of a disease-predisposing mutation will have implications for the etiology, diagnosis, pathogenesis, and treatment of schizophrenia.