Counselling under genetic heterogeneity: a practical approach

Abstract

Hereditary diseases due to mutation at different gene loci may be indistinguishable phenotypically. In these situations genetic risk predictions using polymorphic markers may be hampered if an individual family is not sufficiently informative to permit it to be assigned to one or the other linkage group. To provide the most usefull estimates of risk, the probability of linkage to a particular chromosome region should be determined prior to calculating risk estimates using the marker system. The probability can be calculated directly using the lod score generated for the family. The individual carrier risk is then the average of the carrier risks determined for linkage to different genetic loci, weighted by the probability of linkage to each group. Several examples are provided.