I am currently involved in a study where we have a gene showing both disease association and high differentiation between Africans and Europeans/Asians (as far as we can see from HapMap data). Sorry, I cannot give more details right now.
Anyway, because of this study I finally got around to reading this paper:
Voight BF, Kudaravalli S, Wen X, Pritchard JK.
PLoS Biology 2007 4(3): e72 doi:10.1371/journal.pbio.0040072
The identification of signals of very recent positive selection provides information about the adaptation of modern humans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favor of variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotide polymorphism (SNP) data for signals of recent selection, and apply this to data from the International HapMap Project. In all three continental groups we find widespread signals of recent positive selection. Most signals are region-specific, though a significant excess are shared across groups. Contrary to some earlier low resolution studies that suggested a paucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selection are from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that have substantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Though the relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies of complex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest ~250 signals of recent selection in each population.
I knew of the results already from a talk by Jonathan Pritchard that I attended this summer, but I hadn’t read the paper until now.
The idea is pretty neat: by looking at the haplotypes around a SNP, and how they break down with distance from the SNP, you can spot which SNPs have changed rapidly from low frequency to higher frequency and these SNPs are candidates for being under selection.
This is illustrated nicely in Figure 1 from the paper:
A) Decay of haplotypes in a single region in which a new selected allele (red, center column) is sweeping to fixation, replacing the ancestral allele (blue). Horizontal lines are haplotypes; SNP positions are marked below the haplotype plot using blue for SNPs with intermediate allele frequencies (minor allele >0.2), and red otherwise. For a given SNP, adjacent haplotypes with the same color carry identical genotypes everywhere between that SNP and the central (selected) site. The left- and right-hand sides are sorted separately. Haplotypes are no longer plotted beyond the points at which they become unique.
B) Decay of haplotype homozygosity for ten replicate simulations. When the core SNP is neutral (σ = 0; left side) the haplotype homozygosity decays at similar rates for both ancestral and derived alleles. When the derived alleles are favored (σ = 2Ns = 250; right side), the haplotype homozygosity decays much slower for the derived alleles than for the ancestral alleles. The discrepancy in the overall areas spanned by these two curves forms the basis of our text for selection (iHS).
The citation was (for the benefit of Research Blogging):
Voight, B., Kudaravalli, S., Wen, X., Pritchard, J. (2006). A Map of Recent Positive Selection in the Human Genome. PLoS Biology, 4(3).