Recent genome-wide scans of natural selection in human populations have identified hundreds of candidate adaptive alleles for further study. One of the most compelling candidates is a derived coding variant of the Ectodysplasin A receptor (EDAR), EDARV370A (370A) (Sabeti et al. 2007; Grossman et al. 2010; Kamberov et al. 2013). Analysis of the geographical distribution of 370A revealed that the allele is at a high frequency in East Asian and Native American populations, but is nearly absent in Europeans and Africans (Sabeti et al. 2007). Previous studies using various computational methods demonstrated that the corresponding non-synonymous SNP (rs3827760) shows one of the strongest signals of selection in the human genome (Sabeti et al. 2007; Bryk et al. 2008; Xue et al. 2009; Grossman et al. 2010). In support of this hypothesis, 370A was also shown to associate with several phenotypic changes of epidermal appendages, including hair thickness (Fujimoto et al. 2008a, b), dental morphology (Kimura et al. 2009; Park et al. 2012; Kamberov et al. 2013), and sweat gland density (Kamberov et al. 2013). Equivalent phenotypic changes have been reported in a 370A knock-in mouse model (Kamberov et al. 2013).
