FAILURE TO FIND LINKAGE BETWEEN SCHIZOPHRENIA AND GENETIC-MARKERS ON CHROMOSOME-21

We sought evidence for the involvement of mutations in the amyloid pre cursor protein gene (APP) in the pathogenesis of schizophrenia in two ways. First, linkage analysis was performed in a sample of 24 families multiply affected with schizophrenia. The genotypes were studied for GT12 (D21S210), a highly polymorphic microsatellite marker at the APP locus. Second, we used single strand conformation analysis (SSCA) to s creen for mutations in exon 17 of APP in one affected member from each family and in a sample of 44 unrelated patients. In addition, we look ed for linkage between schizophrenia and a series of highly polymorphi c markers situated at approximately 20cM intervals along the long arm of chromosome 21. We were unable to find evidence for linkage to GT12 or the other markers studied. SSCA did not reveal any mutations in exo n 17 of APP. We conclude that mutations within APP are an unlikely cau se of schizophrenia. Moreover, this study provides no evidence for a m ajor gene for schizophrenia on chromosome 21, and linkage can be exclu ded from much of this region under some genetic models. (C) 1993 Wiley -Liss, Inc.