STRATEGIES FOR STUDYING HETEROGENEOUS GENETIC-TRAITS IN HUMANS BY USING A LINKAGE MAP OF RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISMS

Simple single-gene disorders in humans can be genetically mapped by using traditional methods of linkage analysis and increasingly abundant restriction fragment length polymorphisms (RFLPs). Many human diseases and traits, however, can be expected to be genetically heterogeneous (i.e., caused by only one of several genes), and traditional linkage analysis is much less effective in such circumstances. We present two methods, interval mapping and simultaneous search, designed to exploit the full power of a linkage map of the DNA markers. For the simplest situations, only 1/3 as many affected families are needed to map a heterogeneous trait by using these methods. Only 1/5-1/50 as many are needed to detect that genetic heterogeneity is present.