Multilocus OCA2 genotypes specify human iris colors

被引:46
作者
Frudakis, Tony [1 ]
Terravainen, Timothy [1 ]
Thomas, Matthew [1 ]
机构
[1] Columbia Univ, Dept Stat, New York, NY 10027 USA
关键词
D O I
10.1007/s00439-007-0401-8
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:311 / 326
页数:16
相关论文
共 71 条
[51]   A molecular signature of metastasis in primary solid tumors [J].
Ramaswamy, S ;
Ross, KN ;
Lander, ES ;
Golub, TR .
NATURE GENETICS, 2003, 33 (01) :49-54
[52]   Population structure, admixture, and aging-related phenotypes in African American adults: The cardiovascular health study [J].
Reiner, AP ;
Ziv, E ;
Lind, DL ;
Nievergelt, CM ;
Schork, NJ ;
Cummings, SR ;
Phong, A ;
Burchard, EG ;
Harris, TB ;
Psaty, BM ;
Kwok, PY .
AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 76 (03) :463-477
[53]   A GENE FOR THE MOUSE PINK-EYED DILUTION LOCUS AND FOR HUMAN TYPE-II OCULOCUTANEOUS ALBINISM [J].
RINCHIK, EM ;
BULTMAN, SJ ;
HORSTHEMKE, B ;
LEE, ST ;
STRUNK, KM ;
SPRITZ, RA ;
AVIDANO, KM ;
JONG, MTC ;
NICHOLLS, RD .
NATURE, 1993, 361 (6407) :72-76
[54]   PIGMENTATION PHENOTYPES OF VARIANT EXTENSION LOCUS ALLELES RESULT FROM POINT MUTATIONS THAT ALTER MSH RECEPTOR FUNCTION [J].
ROBBINS, LS ;
NADEAU, JH ;
JOHNSON, KR ;
KELLY, MA ;
ROSELLIREHFUSS, L ;
BAACK, E ;
MOUNTJOY, KG ;
CONE, RD .
CELL, 1993, 72 (06) :827-834
[55]   Clines, clusters, and the effect of study design on the inference of human population structure [J].
Rosenberg, NA ;
Mahajan, S ;
Ramachandran, S ;
Zhao, CF ;
Pritchard, JK ;
Feldman, MW .
PLOS GENETICS, 2005, 1 (06) :660-671
[56]   Genetic structure of human populations [J].
Rosenberg, NA ;
Pritchard, JK ;
Weber, JL ;
Cann, HM ;
Kidd, KK ;
Zhivotovsky, LA ;
Feldman, MW .
SCIENCE, 2002, 298 (5602) :2381-2385
[57]  
Schneider S., 2000, ARLEQUIN VER 2000 SO
[58]  
Shriver Mark D., 2005, Human Genomics, V2, P81
[59]   Genetic ancestry and the search for personalized genetic histories [J].
Shriver, MD ;
Kittles, RA .
NATURE REVIEWS GENETICS, 2004, 5 (08) :611-U3
[60]   Skin pigmentation, biogeographical ancestry and admixture mapping [J].
Shriver, MD ;
Parra, EJ ;
Dios, S ;
Bonilla, C ;
Norton, H ;
Jovel, C ;
Pfaff, C ;
Jones, C ;
Massac, A ;
Cameron, N ;
Baron, A ;
Jackson, T ;
Argyropoulos, G ;
Jin, L ;
Hoggart, CJ ;
McKeigue, PM ;
Kittles, RA .
HUMAN GENETICS, 2003, 112 (04) :387-399