title: A global view of the OCA2-HERC2 region and pigmentation.
abstract: 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. Long-range 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.
authors: Department of Genetics, School of Medicine, Yale University, New Haven, CT 06520, USA.
authors: Michael P
authors: MP
authors: Donnelly
authors: Peristera
authors: P
authors: Paschou
authors: Elena
authors: E
authors: Grigorenko
authors: David
authors: D
authors: Gurwitz
authors: Csaba
authors: C
authors: Barta
authors: Ru-Band
authors: RB
authors: Lu
authors: Olga V
authors: OV
authors: Zhukova
authors: Jong-Jin
authors: JJ
authors: Kim
authors: Marcello
authors: M
authors: Siniscalco
authors: Maria
authors: M
authors: New
authors: Hui
authors: H
authors: Li
authors: Sylvester L B
authors: SL
authors: Kajuna
authors: Vangelis G
authors: VG
authors: Manolopoulos
authors: William C
authors: WC
authors: Speed
authors: Andrew J
authors: AJ
authors: Pakstis
authors: Judith R
authors: JR
authors: Kidd
authors: Kenneth K
authors: KK
authors: Kidd
mesh_terms: D005060:Europe; D005127:Eye Color; D005202:Asia, Eastern; D005787:Gene Frequency; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D026901:Membrane Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D012880:Skin Pigmentation; D044767:Ubiquitin-Protein Ligases
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; C118566:HERC2 protein, human; D044767:Ubiquitin-Protein Ligases