Detecting whether and how natural selection has targeted regions of the human genome represents a complementary strategy for identifying functionally important loci and variants involved in disease resistance and adaptation to the environment. In contrast with most complex diseases or traits, the genetic architecture of most Mendelian traits is relatively well established. Most mutations associated with Mendelian disease-related traits are highly penetrant and kept at low population frequencies because of the effects of purifying selection. However, this is not always the case. Here, we review several examples of Mendelian mutations-associated with various disease conditions or other traits of anthropological interest-that have increased in frequency in the human population as a result of past positive selection. These examples clearly illustrate the value of a population genetics approach to unravel the biological mechanisms that have been central to our past and present survival against the selective pressures imposed by diseases and other environmental factors.
© 2010 New York Academy of Sciences.