With the advent of recombinant DNA technology and the discovery of DNA restriction fragment length polymorphisms(RFLPs) genetic linkage has become an exceptionally powerful tool for understanding the etiology of psychiatric disorders. This project will attempt to find a marker locus linked to a major locus for bipolar affective disorder, major depression, Tourette syndrome, and other major psychiatric disorders. The major emphasis of the proposed research will be the construction of general human linkage map using primarily DNA restriction fragment length polymorphisms. Typing will be done in a few large reference pedigrees, several of which will be studied collaboratively with other groups. Linkage analyses will be done using the computer program LIPED and multipoint mapping methods to be developed as part of the project. Some new reference pedigrees will be collected and permanent lymphoblastoid cell lines established. Once sections of the human map are reasonably complete, the knowledge will be used in studying linkage of the same markers with a psychiatric disorder, e.g., bipolar affective disorder, using existing cell lines and cell lines on additional pedigrees to be collected. RFLPs associated with specific cloned genes of neuropsychiatric interest, e.g., pro-opiomelanocortin, will also be studied in the families with psychiatric disorders to test whether those genes might have variants affecting the disorder. This project will contribute to the development of the general human linkage map, to a better understanding of how the map can be used to clarify the genetics of psychiatric disorders, and to an understanding of the roles of certain genes in mental health.