CONCLUSIONS OF SEGREGATION ANALYSIS FOR FAMILY DATA GENERATED UNDER 2-LOCUS MODELS

Susceptibility to a disease may involve the interactive effect of two genes. What conclusions will be drawn by segregation analysis in such a case? To answer this question, we considered a set of two-locus mode ls and the corresponding exact distribution for 300 families. We inves tigated the conclusions and parameter estimations obtained for this sa mple, by comparing the likelihood expectations of the unified model an d of more restricted models. In many cases, segregation analysis leads to the conclusion of a major gene effect, with or without a polygenic component-usually without a polygenic component in multiplicative mod els (i.e., where two genes have a multiplicative effect) and with such a component in nonmultiplicative models. For all the models considere d, existence of a major gene effect is supported by transmission proba bility tests; there is evidence for transmission and agreement with th e hypothesis of Mendelian transmission. Accordingly, there is no means of detecting that the effect of a major gene, with or without a polyg enic component, does not correspond to the correct model. In addition, the parameter estimates for the major gene do not correspond to the c haracteristics of either of the two genes of the true model. This may substantially affect further linkage analysis.