This multifaceted program of research in the genetics or psychiatric disorder contains elements of basic human genetics and of molecular genetics for selected loci, both relevant to the eventual understanding of the etiologies of neuropsychiatric disorders and the variation in expression of those disorders caused by genetic variation among individuals. The program is also applying the techniques of modern human genetics in genetic linkage paradigms to search for major genes involved in etiology of specific disorders using large kindreds with schizophrenia and with Tourette syndrome. Populations around the world differ, sometimes dramatically, in the frequencies of different alleles for expressed genetic variation. At genes of neuropsychiatric relevance that variation can modify expression of the disorder or may contribute to the liability of developing the disorder. Consequently, a full understanding of the genetic contributions to complex neuropsychiatric disorders, like schizophrenia and tourette syndrome, must include understanding that variation. Elucidating the etiology of major neuropsychiatric disorders is a complex problem that requires multiple approaches. One of those is the use of genetic linkage paradigms to identify regions of the genome containing major genes contributing to etiology. New powerful less hypothesis dependent methods are now being applied to large datasets already in existence and additional markers are improving the informativeness of these kindreds. Linkage disequilibrium will then be a further tool to narrow the region of interest. The identification of such genetic regions will be a strong tool for subsequent improved understanding not only of the genetics of these disorders but also of pathogenesis.
