TY - JOUR

T1 - A global view of the OCA2-HERC2 region and pigmentation

AU - Donnelly, Michael P.

AU - Paschou, Peristera

AU - Grigorenko, Elena

AU - Gurwitz, David

AU - Barta, Csaba

AU - Lu, Ru Band

AU - Zhukova, Olga V.

AU - Kim, Jong Jin

AU - Siniscalco, Marcello

AU - New, Maria

AU - Li, Hui

AU - Kajuna, Sylvester L.B.

AU - Manolopoulos, Vangelis G.

AU - Speed, William C.

AU - Pakstis, Andrew J.

AU - Kidd, Judith R.

AU - Kidd, Kenneth K.

N1 - Funding Information: Acknowledgments This research was funded in part by National Institutes of Health Grant GM57672 and National Institute of Justice, Office of Justice Programs, US Department of Justice Grants 2007-DN-BX-K197, 2010-DN-BX-K225 awarded to KKK. Points of view in this document are those of the authors and do not necessarily represent the official position or policies of the US Department of Justice. We would like to acknowledge all our collaborators who helped collect the samples used in this research as well as the National Laboratory for the Genetics of Israeli Populations at Tel Aviv University and the Coriell Cell Repositories. Finally we would like to thank the thousands of individuals who donated samples without whom this research would not be possible.

PY - 2012/5

Y1 - 2012/5

N2 - Mutations in the gene OCA2 are responsible for oculocutaneous albinism type 2, but polymorphisms in and around OCA2 have also been associated with normal pigment variation. In Europeans, three haplotypes in the region have been shown to be associated with eye pigmentation and a missense SNP (rs1800407) has been associated with green/hazel eyes (Branicki et al. in Ann Hum Genet 73:160-170, 2009). In addition, a missense mutation (rs1800414) is a candidate for light skin pigmentation in East Asia (Yuasa et al. in Biochem Genet 45:535-542, 2007; Anno et al. in Int J Biol Sci 4, 2008). We have genotyped 3,432 individuals from 72 populations for 21 SNPs in the OCA2-HERC2 region including those previously associated with eye or skin pigmentation. We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Longrange haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele of rs1800414 is an East Asian skin pigmentation allele.

AB - Mutations in the gene OCA2 are responsible for oculocutaneous albinism type 2, but polymorphisms in and around OCA2 have also been associated with normal pigment variation. In Europeans, three haplotypes in the region have been shown to be associated with eye pigmentation and a missense SNP (rs1800407) has been associated with green/hazel eyes (Branicki et al. in Ann Hum Genet 73:160-170, 2009). In addition, a missense mutation (rs1800414) is a candidate for light skin pigmentation in East Asia (Yuasa et al. in Biochem Genet 45:535-542, 2007; Anno et al. in Int J Biol Sci 4, 2008). We have genotyped 3,432 individuals from 72 populations for 21 SNPs in the OCA2-HERC2 region including those previously associated with eye or skin pigmentation. We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Longrange haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele of rs1800414 is an East Asian skin pigmentation allele.

UR - http://www.scopus.com/inward/record.url?scp=84862263758&partnerID=8YFLogxK

U2 - 10.1007/s00439-011-1110-x

DO - 10.1007/s00439-011-1110-x

M3 - Article

C2 - 22065085

AN - SCOPUS:84862263758

VL - 131

SP - 683

EP - 696

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 5

ER -