De La Vega Francisco M, Isaac Hadar, Collins Andrew, Scafe Charles R, Halldórsson Bjarni V, Su Xiaoping, Lippert Ross A, Wang Yu, Laig-Webster Marion, Koehler Ryan T, Ziegle Janet S, Wogan Lewis T, Stevens Junko F, Leinen Kyle M, Olson Sheri J, Guegler Karl J, You Xiaoqing, Xu Lily H, Hemken Heinz G, Kalush Francis, Itakura Mitsuo, Zheng Yi, de Thé Guy, O'Brien Stephen J, Clark Andrew G, Istrail Sorin, Hunkapiller Michael W, Spier Eugene G, Gilbert Dennis A
Applied Biosystems, Foster City, California 94404, USA.
Genome Res. 2005 Apr;15(4):454-62. doi: 10.1101/gr.3241705. Epub 2005 Mar 21.
The extent and patterns of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a comparison of the patterns of LD across four major human populations (African-American, Caucasian, Chinese, and Japanese) with a high-resolution single-nucleotide polymorphism (SNP) map covering almost the entire length of chromosomes 6, 21, and 22. We constructed metric LD maps formulated such that the units measure the extent of useful LD for association mapping. LD reaches almost twice as far in chromosome 6 as in chromosomes 21 or 22, in agreement with their differences in recombination rates. By all measures used, out-of-Africa populations showed over a third more LD than African-Americans, highlighting the role of the population's demography in shaping the patterns of LD. Despite those differences, the long-range contour of the LD maps is remarkably similar across the four populations, presumably reflecting common localization of recombination hot spots. Our results have practical implications for the rational design and selection of SNPs for disease association studies.
连锁不平衡(LD)的程度和模式决定了通过关联研究来定位复杂性状相关基因的可行性。在此,我们利用一张覆盖了6号、21号和22号染色体几乎全长的高分辨率单核苷酸多态性(SNP)图谱,对四个主要人类群体(非裔美国人、高加索人、中国人和日本人)中的LD模式进行了比较。我们构建了度量LD图谱,其构建方式使得图谱中的单位能够衡量关联图谱中有用LD的程度。6号染色体上的LD延伸长度几乎是21号或22号染色体的两倍,这与它们在重组率上的差异一致。通过所有使用的衡量方法,走出非洲的群体显示出比非裔美国人多三分之一以上的LD,这突出了群体人口统计学在塑造LD模式中的作用。尽管存在这些差异,但四个群体中LD图谱的长距离轮廓非常相似,推测这反映了重组热点的共同定位。我们的结果对疾病关联研究中SNP的合理设计和选择具有实际意义。