CLOSING IN ON GENES FOR MANIC-DEPRESSIVE ILLNESS AND SCHIZOPHRENIA

Advances in the human genetic map, and in genetic analysis of linkage and association in complex inheritance traits, have led to genetic pro gress in the major psychoses. For chromosome 6 in schizophrenia, and c hromosomes 18 and 21 in manic-depressive illness, there are reports of linkage in several independent data sets. These are small effect gene s, best detected with affected-relative-pair linkage methods. Associat ion with candidate genes is an alternative strategy to uncovering susc eptibility genes for these illnesses, but convincing associations rema in to be demonstrated. New clinical and laboratory investigation metho ds are being developed. Testing every gene in the human genome for ass ociation with illness has recently been proposed (Risch and Merikangas 1996). This would require further progress in characterizing the geno me and in automated large-scale genotyping. The best type of pedigree sampling for common disease studies, whether for linkage or associatio n, is not yet established. An endophenotype hybrid strategy can combin e genetic linkage, association, and pathophysiologic studies. As clini cal molecular investigation methods advance, identification of disease susceptibility mutations and delineation of their pathophysiological roles may be expected. Published by Elsevier Science Inc.