Two-disease-locus model: segregation analysis using information on two markers in nuclear families. Application to IDDM.

In the present paper, an extension of segregation analysis is proposed using information on the joint segregation of two unlinked markers conditional on the disease status in nuclear families, in order to consider two-locus models with one locus linked to the first marker and the other linked to the second marker. We propose tests for examining evidence for the effect of genes located at these two loci and whether this effect is multiplicative or not. This method is then applied to a sample of IDDM families typed for the HLA and Gm markers to test, in addition to a factor of the HLA region, the potential involvement of the Gm system in the susceptibility to IDDM. The analysis does not provide evidence for such an involvement.