title: Skin pigmentation, biogeographical ancestry and admixture mapping.
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 (R(2)=0.21, P<0.0001 for the African-American sample and R(2)=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.
authors.affiliation: Department of Anthropology, Penn State University, 409 Carpenter Bld., University Park, PA 16802, USA. mds17@psu.edu
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
authors.forename: Esteban J
authors.initials: EJ
authors.lastname: Parra
authors.forename: Sonia
authors.initials: S
authors.lastname: Dios
authors.forename: Carolina
authors.initials: C
authors.lastname: Bonilla
authors.forename: Heather
authors.initials: H
authors.lastname: Norton
authors.forename: Celina
authors.initials: C
authors.lastname: Jovel
authors.forename: Carrie
authors.initials: C
authors.lastname: Pfaff
authors.forename: Cecily
authors.initials: C
authors.lastname: Jones
authors.forename: Aisha
authors.initials: A
authors.lastname: Massac
authors.forename: Neil
authors.initials: N
authors.lastname: Cameron
authors.forename: Archie
authors.initials: A
authors.lastname: Baron
authors.forename: Tabitha
authors.initials: T
authors.lastname: Jackson
authors.forename: George
authors.initials: G
authors.lastname: Argyropoulos
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Hoggart
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKeigue
authors.forename: Rick A
authors.initials: RA
authors.lastname: Kittles
mesh_terms: D000349:Africa / Q000208:ethnology; D001741:Black or African American / Q000706:statistics & numerical data; D044383:Black People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D005060:Europe / Q000208:ethnology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D014442:Monophenol Monooxygenase / Q000235:genetics*; D018043:Receptors, Corticotropin / Q000235:genetics*; D044101:Receptors, Melanocortin; D012880:Skin Pigmentation / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology; D014900:West Indies / Q000208:ethnology; D044465:White People / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D014442:Monophenol Monooxygenase