Human genetic individuality.

The central preoccupation of human genetics is an effort to understand the genotypic basis of human phenotypic diversity. Although recent progress in identifying the genes that, when mutated, underlie major genetic diseases has been rapid, knowledge of the genetic influences on the vast range of variable, and at least partially heritable, traits that constitute the "normal" range of human phenotypic variation lags. Spectacular advances in our knowledge of human genetic variation have laid the groundwork for a synthesis of insights from medical genetics, population genetics, molecular evolution, and the study of human origins that places basic constraints on models of human genetic individuality. Balancing selection, local adaptation, mutation-selection balance, and founder effects have all extensively shaped contemporary genetic variation. Long-term-balancing selection appears largely to reflect the consequences of host-pathogen arms races. Local adaptation has been widespread-and involved responses to a plethora of selective pressures, some identifiable but most unknown. However, it appears to be a combination of mutation-selection balance and founder effects that largely accounts for genetic individuality. If true, this inference has major implications for future research programs in human genetics.