Beaty T H, Fallin M D, Hetmanski J B, McIntosh I, Chong S S, Ingersoll R, Sheng X, Chakraborty R, Scott A F
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Genetics. 2005 Sep;171(1):259-67. doi: 10.1534/genetics.105.043075. Epub 2005 Jun 18.
Analysis of haplotypes based on multiple single-nucleotide polymorphisms (SNP) is becoming common for both candidate gene and fine-mapping studies. Before embarking on studies of haplotypes from genetically distinct populations, however, it is important to consider variation both in linkage disequilibrium (LD) and in haplotype frequencies within and across populations, as both vary. Such diversity will influence the choice of "tagging" SNPs for candidate gene or whole-genome association studies because some markers will not be polymorphic in all samples and some haplotypes will be poorly represented or completely absent. Here we analyze 11 genes, originally chosen as candidate genes for oral clefts, where multiple markers were genotyped on individuals from four populations. Estimated haplotype frequencies, measures of pairwise LD, and genetic diversity were computed for 135 European-Americans, 57 Chinese-Singaporeans, 45 Malay-Singaporeans, and 46 Indian-Singaporeans. Patterns of pairwise LD were compared across these four populations and haplotype frequencies were used to assess genetic variation. Although these populations are fairly similar in allele frequencies and overall patterns of LD, both haplotype frequencies and genetic diversity varied significantly across populations. Such haplotype diversity has implications for designing studies of association involving samples from genetically distinct populations.
基于多个单核苷酸多态性（SNP）的单倍型分析在候选基因研究和精细定位研究中都越来越普遍。然而，在开始对遗传上不同的人群进行单倍型研究之前，重要的是要考虑连锁不平衡（LD）以及人群内部和人群之间单倍型频率的变化，因为两者都会有所不同。这种多样性将影响候选基因或全基因组关联研究中“标签”SNP的选择，因为某些标记在所有样本中不会是多态性的，并且某些单倍型的代表性较差或完全不存在。在这里，我们分析了11个最初被选为口腔腭裂候选基因的基因，对来自四个人群的个体进行了多个标记的基因分型。计算了135名欧裔美国人、57名新加坡华人、45名新加坡马来人和46名新加坡印度人的估计单倍型频率、成对LD的测量值和遗传多样性。比较了这四个人群之间的成对LD模式，并使用单倍型频率来评估遗传变异。尽管这些人群在等位基因频率和LD的总体模式上相当相似，但单倍型频率和遗传多样性在不同人群之间都有显著差异。这种单倍型多样性对设计涉及来自遗传上不同人群样本的关联研究具有重要意义。
