Willer Cristen J, Scott Laura J, Bonnycastle Lori L, Jackson Anne U, Chines Peter, Pruim Randall, Bark Craig W, Tsai Ya-Yu, Pugh Elizabeth W, Doheny Kimberly F, Kinnunen Leena, Mohlke Karen L, Valle Timo T, Bergman Richard N, Tuomilehto Jaakko, Collins Francis S, Boehnke Michael
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, USA.
Genet Epidemiol. 2006 Feb;30(2):180-90. doi: 10.1002/gepi.20131.
The pattern and nature of linkage disequilibrium in the human genome is being studied and catalogued as part of the International HapMap Project [:2003 Nature 426:789-796]. A key goal of the HapMap Project is to enable identification of tag single nucleotide polymorphisms (SNPs) that capture a substantial portion of common human genetic variability while requiring only a small fraction of SNPs to be genotyped [International HapMap Consortium, 2005: Nature 437:1299-1320]. In the current study, we examined the effectiveness of using the CEU HapMap database to select tag SNPs for a Finnish sample. We selected SNPs in a 17.9-Mb region of chromosome 14 based on pairwise linkage disequilibrium (r(2)) estimates from the HapMap CEU sample, and genotyped 956 of these SNPs in 1,425 Finnish individuals. An excess of SNPs showed significantly different allele frequencies between the HapMap CEU and the Finnish samples, consistent with population-specific differences. However, we observed strong correlations between the two samples for estimates of allele frequencies, r(2) values, and haplotype frequencies. Our results demonstrate that the HapMap CEU samples provide an adequate basis for tag SNP selection in Finnish individuals, without the need to create a map specifically for the Finnish population, and suggest that the four-population HapMap data will provide useful information for tag SNP selection beyond the specific populations from which they were sampled.
作为国际人类基因组单体型图计划的一部分，人类基因组中连锁不平衡的模式和性质正在被研究并编目（参考文献：2003年《自然》杂志第426卷，第789 - 796页）。人类基因组单体型图计划的一个关键目标是能够识别标签单核苷酸多态性（SNP），这些标签SNP能够捕获大部分常见的人类遗传变异，同时只需对一小部分SNP进行基因分型（国际人类基因组单体型图联盟，2005年：《自然》杂志第437卷，第1299 - 1320页）。在当前研究中，我们检验了使用CEU人类基因组单体型图数据库为芬兰样本选择标签SNP的有效性。我们基于人类基因组单体型图CEU样本的成对连锁不平衡（r²）估计值，在14号染色体的一个17.9兆碱基区域选择了SNP，并在1425名芬兰个体中对其中956个SNP进行了基因分型。大量的SNP在人类基因组单体型图CEU样本和芬兰样本之间显示出显著不同的等位基因频率，这与人群特异性差异一致。然而，我们观察到两个样本在等位基因频率估计值、r²值和单倍型频率方面存在很强的相关性。我们的结果表明，人类基因组单体型图CEU样本为芬兰个体的标签SNP选择提供了充分的基础，无需专门为芬兰人群创建图谱，并表明四个人群的人类基因组单体型图数据将为标签SNP选择提供有用信息，而不仅仅局限于从中抽样的特定人群。
