Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene
Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene
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DOI：
10.1016/j.ajhg.2007.10.003
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发表时间：
2008-02-01
影响因子：
9.8
通讯作者：
van Duijn, Cornelia M.
中科院分区：
文献类型：
--
作者：
Kayser, Manfred;Liu, Fan;van Duijn, Cornelia M.
人类虹膜颜色是孟德尔分离理论最早建立的特征之一。到目前为止，虹膜颜色的遗传学仍然没有完全理解和兴趣，特别是考虑到法医应用。在三个独立的全基因组关联（GWA）研究中，共有1406人，以及1292个亲属的全基因组连锁研究，都来自荷兰，我们发现15q13.1区域是人类虹膜颜色的主要区域。没有其他区域显示一致的全基因组证据与虹膜颜色的关联和联系。HERC2基因的单核苷酸多态性（snp）以及邻近的OCA2基因的单核苷酸多态性（snp）在较小程度上与虹膜颜色变化独立相关。OCA2先前与虹膜颜色有关。在两个人群中的复制研究证实，HERC2基因是人类虹膜颜色变异的一个新的和重要的决定因素，除了OCA2。此外，HERC2 rs916977等位基因在23个欧洲人群中的临床分布与虹膜颜色变异显著相关。我们认为，调节OCA2基因表达的遗传变异存在于HERC2基因中，或者存在于OCA2和HERC2之间11.7 kb的序列中，欧洲人的大多数虹膜颜色变异都是由这两个基因解释的。检测HERC2-OCA2区域的标记物可能在法医应用中用于预测欧洲遗传来源的未知人群的眼睛颜色表型。
Human iris color was one of the first traits for which Mendelian segregation was established. To date, the genetics of iris color is still not fully understood and is of interest, particularly in view of forensic applications. In three independent genome-wide association (GWA) studies of a total of 1406 persons and a genome-wide linkage study of 1292 relatives, all from the Netherlands, we found that the 15q13.1 region is the predominant region involved in human iris color. There were no other regions showing consistent genome-wide evidence for association and linkage to iris color. Single nucleotide polymorphisms (SNPs) in the HERC2 gene and, to a lesser extent, in the neighboring OCA2 gene were independently associated to iris color variation. OCA2 has been implicated in iris color previously. A replication study within two populations confirmed that the HERC2 gene is a new and significant determinant of human iris color variation, in addition to OCA2. Furthermore, HERC2 rs916977 showed a clinal allele distribution across 23 European populations, which was significantly correlated to iris color variation. We suggest that genetic variants regulating expression of the OCA2 gene exist in the HERC2 gene or, alternatively, within the 11.7 kb of sequence between OCA2 and HERC2, and that most iris color variation in Europeans is explained by those two genes. Testing markers in the HERC2-OCA2 region may be useful in forensic applications to predict eye color phenotypes of unknown persons of European genetic origin.