Original Investigation

Human Genetics

, Volume 112, Issue 4, pp 387-399

First online:

Skin pigmentation, biogeographical ancestry and admixture mapping

  • Mark D. ShriverAffiliated withDepartment of Anthropology, Penn State University Email author 
  • , Esteban J. ParraAffiliated withDepartment of Anthropology, Penn State UniversityDepartment of Anthropology, University of Toronto at Mississauga
  • , Sonia DiosAffiliated withDepartment of Anthropology, Penn State University
  • , Carolina BonillaAffiliated withDepartment of Anthropology, Penn State University
  • , Heather NortonAffiliated withDepartment of Anthropology, Penn State University
  • , Celina JovelAffiliated withDepartment of Anthropology, Penn State University
  • , Carrie PfaffAffiliated withDepartment of Anthropology, Penn State University
  • , Cecily JonesAffiliated withNational Human Genome Center, Howard University
  • , Aisha MassacAffiliated withNational Human Genome Center, Howard University
    • , Neil CameronAffiliated withTakeway Media
    • , Archie BaronAffiliated withTakeway Media
    • , Tabitha JacksonAffiliated withTakeway Media
    • , George ArgyropoulosAffiliated withPennington Center for Biomedical Research
    • , Li JinAffiliated withDepartment of Environmental Health University of Cincinnati
    • , Clive J. HoggartAffiliated withDepartment of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine
    • , Paul M. McKeigueAffiliated withDepartment of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine
    • , Rick A. KittlesAffiliated withNational Human Genome Center, Howard University

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Abstract

Ancestry informative markers (AIMs) are genetic loci showing alleles with large frequency differences between populations. AIMs can be used to estimate biogeographical ancestry at the level of the population, subgroup (e.g. cases and controls) and individual. Ancestry estimates at both the subgroup and individual level can be directly instructive regarding the genetics of the phenotypes that differ qualitatively or in frequency between populations. These estimates can provide a compelling foundation for the use of admixture mapping (AM) methods to identify the genes underlying these traits. We present details of a panel of 34 AIMs and demonstrate how such studies can proceed, by using skin pigmentation as a model phenotype. We have genotyped these markers in two population samples with primarily African ancestry, viz. African Americans from Washington D.C. and an African Caribbean sample from Britain, and in a sample of European Americans from Pennsylvania. In the two African population samples, we observed significant correlations between estimates of individual ancestry and skin pigmentation as measured by reflectometry (R2=0.21, P<0.0001 for the African-American sample and R2=0.16, P<0.0001 for the British African-Caribbean sample). These correlations confirm the validity of the ancestry estimates and also indicate the high level of population structure related to admixture, a level that characterizes these populations and that is detectable by using other tests to identify genetic structure. We have also applied two methods of admixture mapping to test for the effects of three candidate genes (TYR, OCA2, MC1R) on pigmentation. We show that TYR and OCA2 have measurable effects on skin pigmentation differences between the west African and west European parental populations. This work indicates that it is possible to estimate the individual ancestry of a person based on DNA analysis with a reasonable number of well-defined genetic markers. The implications and applications of ancestry estimates in biomedical research are discussed.