Skin and hair pigmentation varies greatly among human populations and most of the genetic basis for this variation is unknown. We recruited 791 individuals to the study at the University of Arizona in Tucson. To measure pigmentary phenotypes, we used reflectance spectrophotometry to measure skin color and we used a standard chemical method to measure the content of two types of pigment, eumelanin and pheomelanin, of hairs collected from each participant.;Skin reflectance is high in self-identified European Americans and low, with very little overlap, in self-identified African Americans. The other groups have intermediate levels of skin reflectance that are generally closer to those of European Americans. The distribution of hair pheomelanin is the most diverse in European Americans, and hair eumelanin content is lower in European Americans than in other groups. Individuals with high levels of pheomelanin and low levels of eumelanin have red hair; individuals with low pheomelanin and medium to high eumelanin levels have dark hair; and individuals with low pheomelanin and eumelanin levels have blond to light brown hair.;To control for the effects of self-reported ethnicity on pigmentary phenotype, we estimate genetic ancestry using 44 Ancestry Informative Markers (AIMs). We examined the genetic structure of 228 individuals from Tucson together with 60 individuals of three distinct reference populations (African, Asian, and European) from the HapMap consortium. We found that individuals of self-identified European American ethnicity are homogenous whereas Hispanics and African Americans have a range of admixture from European ancestry and Native American or African ancestry, respectively. Individuals of South Asian and East Asian ethnicity have a substantial amount of European and Asian admixture; South Asians have more European ancestry and East Asians have more Asian ancestry.;To identify genetic determinants of human pigmentation, we resequenced regions in 7 candidate genes and tested the association between single nucleotide polymorphisms (SNPs) in the candidate genes and quantitative and qualitative measures of human pigmentation in European Americans. We test association of 24 single nucleotide polymorphisms (SNPs) at MC1R, 8 at ASIP, 36 at OCA2, 9 at MATP, 10 at SLC24A5, 16 at TYR, and 56 at TYRP1 in 112 European Americans. Of these, 34 SNPs were associated with quantitative traits (hair melanin content and skin reflectance) at the 5% significance level. Using an evolutionary-based approach to study protein polymorphisms, we found that European Americans with MC1R variants with predicted decreased function are associated with higher hair pheomelanin content.;Our analyses identify potential genetic factors responsible for pigmentary variation in European Americans. Together with the estimates of genetic ancestry and characterization of pigmentary phenotype, this work provides insight into the genetic architecture of human pigmentation.
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