Open AccessImportance of nonsynonymous OCA 2 variants in human eye color prediction
Author(s) -
Andersen Jeppe D.,
Pietroni Carlotta,
Johansen Peter,
Andersen Mikkel M.,
Pereira Vania,
Børsting Claus,
Morling Niels
Publication year - 2016
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.213
Subject(s) - nonsynonymous substitution , single nucleotide polymorphism , eye color , genetics , snp , phenotype , biology , haplotype , microbiology and biotechnology , genotype , gene , genome
Background The color of the eyes is one of the most prominent phenotypes in humans and it is often used to describe the appearance of an individual. The intensity of pigmentation in the iris is strongly associated with one single‐nucleotide polymorphism ( SNP ), rs12913832:A>G that is located in the promotor region of OCA 2 ( OMIM #611409). Nevertheless, many eye colors cannot be explained by only considering rs12913832:A>G. Methods In this study, we searched for additional variants in OCA 2 to explain human eye color by sequencing a 500 kbp region, encompassing OCA 2 and its promotor region. Results We identified three nonsynonymous OCA 2 variants as important for eye color, including rs1800407:G>A (p.Arg419Gln) and two variants, rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile), not previously described as important for eye color variation. It was shown that estimated haplotypes consisting of four variants (rs12913832:A>G, rs1800407:G>A (p.Arg419Gln), rs74653330:A>T (p.Ala481Thr), and rs121918166:G>A (p.Val443Ile)) explained 75.6% (adjusted R 2 = 0.76) of normal eye color variation, whereas rs12913832:A>G alone explained 68.8% (adjusted R 2 = 0.69). Moreover, rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile) had a measurable effect on quantitative skin color ( P = 0.008). Conclusion Our data showed that rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile) have a measurable effect on normal pigmentation variation.