Multilocus OCA2 genotypes specify human iris colors

Abstract

Human iris color is a quantitative, multifactorial phenotype that exhibits quasi-Mendelian inheritance. Recent studies have shown that OCA2 polymorphism underlies most of the natural variability in human iris pigmentation but to date, only a few associated polymorphisms in this gene have been described. Herein, we describe an iris color score (C) for quantifying iris melanin content in-silico and undertake a more detailed survey of the OCA2 locus (n = 271 SNPs). In 1,317 subjects, we confirmed six previously described associations and identified another 27 strongly associated with C that were not explained by continental population stratification (OR 1.5-17.9, P = 0.03 to <0.001). Haplotype analysis with respect to these 33 SNPs revealed six haplotype blocks and 11 hap-tags within these blocks. To identify genetic features for best-predicting iris color, we selected sets of SNPs by parsing P values among possible combinations and identified four discontinuous and non-overlapping sets across the LD blocks (p-Selected SNP sets). In a second, partially overlapping sample of 1,072, samples with matching diplotypes comprised of these p-Selected OCA2 SNPs exhibited a rate of C concordance of 96.3% (n = 82), which was significantly greater than that obtained from randomly selected samples (62.6%, n = 246, P<0.0001). In contrast, the rate of C concordance using diplotypes comprised of the 11 identified hap-tags was only 83.7%, and that obtained using diplotypes comprised of all 33 SNPs organized as contiguous sets along the locus (defined by the LD block structure) was only 93.3%. These results confirm that OCA2 is the major human iris color gene and suggest that using an empirical database-driven system, genotypes from a modest number of SNPs within this gene can be used to accurately predict iris melanin content from DNA.

Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression

“…Attempts to identify the BEY/blue mutations in OCA2 have failed (Frudakis et al 2007), and a variation within the 5Ј proximal regulatory control region of OCA2 was suggested to be responsible for 90% of the eye color pigmentation variation (DuVy et al 2007).…”

Forensic DNA Phenotyping: Predicting human appearance from crime scene material for investigative purposes

“…Frudakis et al [12] used 33 SNPs from the OCA2 gene, which allowed them to classify 8% of the eye colors observed among >1000 samples. Sulem et al [13], embedded in the first GWAS on human pigmentation traits, used 9 SNPs from 6 genomic regions (SLC24A4, KITLG, 6p25.3, TYR, OCA2-HERC2, and MC1R) which they identified with significant eye color association among several thousand Europeans, for categorical eye color prediction.…”

Single Nucleotide Polymorphisms in Forensic Applications Based on Identification: Review

“…42 Ardından HERC2, OCA2, SLC24A4, SLC45A2, TYR ve IRF4 genleri ile çalışmalar yapılmıştır. [43][44][45][46][47][48] Son dönemlerde, bu çalış-malardan elde edilen bilgiler ışığında mavi ve kahverengi göz rengi tahminine yardımcı olmak için "IrisPlex" test kiti geliştirilmiştir. Altı SNP (HERC2, OCA2, SLC24A4, SLC45A2, TYR ve IRF4)'nin birlikte analizinin yapıldığı "IrisPlex" testinin duyarlı-lık ve özgüllük gibi adli validasyon çalışmalarının da yapıldığı belirtilmektedir.…”