Close linkage of c-Harvey-ras-1 and the insulin gene to affective disorder is ruled out in three North American pedigrees.

Affective disorder (AD) is one of the major forms of functional psychoses. Although the mode of transmission is uncertain, family, twin and adoption studies strongly suggest a genetic involvement. Because a basic biochemical abnormality is not known, direct analysis of the disease using a probe for the defective gene is not possible. However, a specific locus can be tested for its relevance to the aetiology of AD by genetic linkage, using restriction fragment length polymorphisms (RFLPs). Using probes for the c-Ha-ras-1 oncogene and the insulin gene, Gerhard et al. and Egeland et al. found convincing evidence for close linkage between these markers and a locus for AD in a large Old Order Amish pedigree. In an attempt to confirm this finding, we examined three bipolar pedigrees outside the Amish population. Our results indicate the absence of linkage from 0 to 15% recombination frequency between AD and the insulin gene-HRAS1 region in these pedigrees.