Importance of non-synonymous OCA2 variants in human eye colour prediction

TY - JOUR

T1 - Importance of non-synonymous OCA2 variants in human eye colour prediction

AU - Andersen, Jeppe Dyrberg

AU - Pietroni, Carlotta

AU - Johansen, Peter

AU - Andersen, Mikkel Meyer

AU - Pereira, Vania

AU - Børsting, Claus

AU - Morling, Niels

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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 OCA2 (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 OCA2 to explain human eye color by sequencing a 500 kbp region, encompassing OCA2 and its promotor region.Results: We identified three nonsynonymous OCA2 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 R2 = 0.76) of normal eye color variation, whereas rs12913832:A>G alone explained 68.8% (adjusted R2 = 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.

AB - 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 OCA2 (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 OCA2 to explain human eye color by sequencing a 500 kbp region, encompassing OCA2 and its promotor region.Results: We identified three nonsynonymous OCA2 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 R2 = 0.76) of normal eye color variation, whereas rs12913832:A>G alone explained 68.8% (adjusted R2 = 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.

U2 - 10.1002/mgg3.213

DO - 10.1002/mgg3.213

M3 - Journal article

C2 - 27468418

SN - 2324-9269

VL - 4

SP - 420

EP - 430

JO - Molecular Genetics & Genomic Medicine

JF - Molecular Genetics & Genomic Medicine

IS - 4

ER -