非同义OCA2变体在人类眼睛颜色预测中的重要性。
Importance of nonsynonymous OCA2 variants in human eye color prediction.
作者信息
Andersen Jeppe D, Pietroni Carlotta, Johansen Peter, Andersen Mikkel M, Pereira Vania, Børsting Claus, Morling Niels
机构信息
Section of Forensic Genetics Department of Forensic Medicine Faculty of Health and Medical Sciences University of Copenhagen DK-2100 Copenhagen Denmark.
Department of Mathematical Sciences Aalborg University DK-9000 Aalborg Denmark.
出版信息
Mol Genet Genomic Med. 2016 Mar 11;4(4):420-30. doi: 10.1002/mgg3.213. eCollection 2016 Jul.
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 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.
背景
眼睛颜色是人类最显著的表型之一，常用于描述个体外貌。虹膜色素沉着强度与位于OCA2（OMIM #611409）启动子区域的一个单核苷酸多态性（SNP）rs12913832:A>G密切相关。然而，仅考虑rs12913832:A>G并不能解释所有的眼睛颜色。
方法
在本研究中，我们通过对包含OCA2及其启动子区域的500 kbp区域进行测序，寻找OCA2中的其他变异，以解释人类眼睛颜色。
结果
我们鉴定出三个非同义OCA2变异对眼睛颜色很重要，包括rs1800407:G>A（p.Arg419Gln）以及两个此前未被描述为对眼睛颜色变异重要的变异，rs74653330:A>T（p.Ala481Thr）和rs121918166:G>A（p.Val443Ile）。结果显示，由四个变异（rs12913832:A>G、rs1800407:G>A（p.Arg419Gln）、rs74653330:A>T（p.Ala481Thr）和rs121918166:G>A（p.Val443Ile））组成的估计单倍型解释了正常眼睛颜色变异的75.6%（调整后R(2)=0.76），而仅rs12913832:A>G解释了68.8%（调整后R(2)=0.69）。此外，rs74653330:A>T（p.Ala481Thr）和rs121918166:G>A（p.Val443Ile）对定量肤色有可测量的影响（P = 0.008）。
结论
我们的数据表明，rs74653330:A>T（p.Ala481Thr）和rs121918166:G>A（p.Val443Ile）对正常色素沉着变异有可测量的影响。
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