The distinctive geographic patterns of common pigmentation variants at the OCA2 gene

Abstract

Oculocutaneous Albinism type 2 (OCA2) is a gene of great interest because of genetic variation affecting normal pigmentation variation in humans. The diverse geographic patterns for variant frequencies at OCA2 have been evident but have not been systematically investigated, especially outside of Europe. Here we examine population genetic variation in and near the OCA2 gene from a worldwide perspective. The very different patterns of genetic variation found across world regions suggest strong selection effects may have been at work over time. For example, analyses involving the variants that affect pigmentation of the iris argue that the derived allele of the rs1800407 single nucleotide polymorphism, which produces a hypomorphic protein, may have contributed to the previously demonstrated positive selection in Europe for the enhancer variant responsible for light eye color. More study is needed on the relationships of the genetic variation at OCA2 to variation in pigmentation in areas beyond Europe.

Investigating the genetic architecture of eye colour in a Canadian cohort

“…Currently, it includes two SNPs in the OCA2/HERC2 region (rs12913832 and rs1800407). The rs1800407 SNP is a missense SNP in OCA2, known to be involved in pigmentation variation ( Donnelly et al., 2012 ; Pospiech et al., 2014 ; Kidd et al., 2020 ). This SNP did not pass the quality control in our study, but other SNPs in high LD are not within the fine-mapped 95% credible sets.…”

The Two Single Nucleotide Polymorphism Haplotypes on Chromosome 15 of the Herc2 and Oca2 Genes of the Color Variation of the Human Eye in a Sample of Iraqi Population

“…A study in Saudi population (1) observed the SNP rs1800407 was not polymorphic in the Saudi population with the presence of the allele G. In this study, concluded the rs1800407 indicating of eye color with the rs12913832 because of the linkage disequilibrium coefficient between alleles of these SNPs strong associated with eye color. Irises exhibit extensive variation across Europe and a small degree of pigmentation from blue to green and brown in North Africa, Middle East, and Asia (8).…”

CNest: A Novel Copy Number Association Discovery Method Uncovers 862 New Associations from 200,629 Whole Exome Sequence Datasets in the UK Biobank

“…particularly strong signal is found in a region containing the OCA2 and HERC2 genes with a -log10 P > 230. Both OCA2 and HERC2 are well known genes involved in pigmentation in both humans and mice and have been shown to be involved in iris, skin and hair pigmentation in human (66)(67)(68)(69). Pathogenic variation in OCA2 including CNVs are known to be a leading cause of the rare genetic disorder oculocutaneous albinism and an increased susceptibility to melanoma (70)(71)(72).…”

“…For example, for hair colour (Figure 2A) after fine mapping we detect 30 copy number variable regions that pass genome wide significance, the majority of which (20/30) have been found to be associated with pigmentation by previous SNP GWAS (Supplementary particularly strong signal is found in a region containing the OCA2 and HERC2 genes with a -log10 P > 230. Both OCA2 and HERC2 are well known genes involved in pigmentation in both humans and mice and have been shown to be involved in iris, skin and hair pigmentation in human (66)(67)(68)(69). Pathogenic variation in OCA2 including CNVs are known to be a leading cause of the rare genetic disorder oculocutaneous albinism and an increased susceptibility to melanoma (70)(71)(72).…”