Em summarizes

Andres et al. 2009. Targets of balancing selection in the human genome. Molecular Biology and Evolution

While genome scans have been successfully used to find the signature of purifying selection, finding evidence of balancing selection is more difficult. Andres et al. approach this problem, scanning human coding seuqnece for evidence long-term balancing selection, which should leave narrow regions of excess polymorphism. They used sequence data from 13,400 genes in 39 humans (two populations) to construct a demographic model and then tested for balancing selection in the 4,877 genes which had 10+ polymorphic or divergent sites. They conducted a two part test: first they used a modified HKA test to detect genes that showed an excess of polymorphism relative to variation. Second, they looked at each gene's allele frequency spectrum and found genes with an excess of intermediate-frequency alleles. They identified 60 genes that deviated from the expectations set by the neutral demographic model in both tests. An MHC gene which was previously known to be under balancing selection was included in this set, validating their results. They also found that on average these 60 genes had higher LD than the rest of the genome, consistent with there being positive epistasis between sites.