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Pubmed ID :18252221
Publication Date : //

Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene.


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.

Authors : Kayser Manfred , Liu Fan , Janssens A Cecile J W , Rivadeneira Fernando , Lao Oscar , van Duijn Kate , Vermeulen Mark , Arp Pascal , Jhamai Mila M , van Ijcken Wilfred F J , den Dunnen Johan T , Heath Simon , Zelenika Diana , Despriet Dominiek D G , Klaver Caroline C W , Vingerling Johannes R , de Jong Paulus T V M , Hofman Albert , Aulchenko Yurii S , Uitterlinden Andre G , Oostra Ben A , van Duijn Cornelia M ,

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