This project is centered on utilizing an extensive upcoming resource of the largest multilocus study of autosomal variation in Africa to date, 3.4 million genotypes derived from 1,165 dispersed microsatellite and in-del markers typed in 80 ethnic population samples across Africa. This resource will be used to characterize population structure within Africa, refine association mapping approaches that can benefit future medical research, and perhaps discover how humans have evolved by positive selection to cope with environmental challenges (of which a significant proportion likely result from either infectious disease resistance or environmental toxins, and thus may be pertinent to immune defense systems and the metabolism of pharmaceutical drugs). In particular, knowledge of both the (possibly cryptic) genetic population boundaries within Africa, as well as the locus specific signals of positive selection, has important implications for the design and implementation of tailored pharmacogenetic/epidemiologic programs in Africa and in populations of a recent African origin, a region with a high incidence of disease in dire need of safe and effective medical interventions. [unreadable] [unreadable] [unreadable]