Assessing linkage disequilibrium in a complex genetic system. I. Overall deviation from random association

Linkage disequilibrium is an important tool both at the end stages of posit ional cloning studies to map genes of particular interest and in reconstruc tion of population histories. With advances in molecular biology, complex g enetic systems involving multiple highly polymorphic markers are becoming m ore commonly used to study linkage disequilibrium, These systems contain mu ch more genetic information than simple two marker systems. In this article , rye introduce a measure to summarize the overall deviation from random as sociation and propose a permutation-based estimate for this measure. The pe rformance of the proposed estimation procedure is studied through simulatio ns. The methods proposed in this paper are then applied to population data at the dopamine D2 receptor locus (DRD2) and at the homeobox B (HOXB) gene cluster.