Living the high life: high-altitude adaptation

There is widespread interest in the identification of human genes subject to positive selection, in part because they may elucidate the biological basis of human adaptation to novel environments and, therefore, may lead to the identification of genes and variants that play a role in disease susceptibility. To this end, a number of computational approaches have been developed to perform scans for positive selection. Unlike demographic processes such as migration, population expansion and bottlenecks, which affect whole-genome patterns of variation, positive selection shapes variation in a locus-specific manner.Furthermore, populations in divergent environments with distinct selective pressures may be subject to local adaptation. Genetic variants that are targets of positive selection in locally adapted populations are expected to show higher levels of population differentiation (that is, differences between populations) and, in some cases, extended regions of allelic association or linkage disequilibrium. Thus, genome-wide scans for selection often identify outliers in the empirical distribution of summary statistics that characterize population differentiation, linkage disequilibrium or some combination of the two, and these outliers are enriched for loci that have been subject to positive selection (reviewed in [1]).One of the classic examples of adaptation to a novel environment is adaptation to high-altitude. At high-altitude, differences in barometric pressure result in insufficient oxygen in the air, thereby causing hypoxia (that is, reduced oxygen levels in the blood). People at high-altitude for short periods of time, who are not adapted to that environment, are at increased risk for acute altitude sickness involving pulmonary and cerebral edema, and after extended periods of time at high-altitude, for chronic altitude sickness involving pulmonary hypertension and related complications. Moreover, pregnant women living in high-altitude environments are at incr