The extent of linkage disequilibrium in four populations with distinct demographic histories
The extent of linkage disequilibrium in four populations with distinct demographic histories
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DOI：
10.1086/316906
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发表时间：
2000-12-01
影响因子：
9.8
通讯作者：
Ponder, BAJ
中科院分区：
文献类型：
--
作者：
Dunning, AM;Durocher, F;Ponder, BAJ
全基因组关联研究的设计和可行性严重依赖于标记间连锁不平衡的程度。虽然有广泛的理论讨论，这一点，很少有经验数据存在。作者在38个次要等位基因频率> 0.1的双等位基因标记中确定了LD的程度，因为这些标记与关联研究旨在检测的常见疾病易感性多态性最具可比性。标记来自三个染色体区域-染色体13 q12 -13上的1，335 kb，染色体19q13.2上的380 kb和染色体22q13.3上的120 kb-已被广泛定位。这些标记在来自四个人群的1,600名个体中进行了检测，这些人都是欧洲人，但有不同的人口统计学历史;南非白人，德系犹太人，芬兰人和东盎格鲁英国人。有几个差异，无论是在等位基因频率或LD，研究人群之间。在每个基因组区域和每个群体中，LD与距离之间存在类似的反比关系。对于500 kb的标记对，平均D'为0.68。然而，只有50%的标记对距离.3）是有用的关联研究。本研究的结果，如果能代表整个基因组，则表明全基因组扫描寻找常见的疾病易感等位基因需要间隔小于或等于5 kb的标记。
The design and feasibility of whole-genome-association studies are critically dependent on the extent of linkage disequilibrium (LD) between markers. Although there has been extensive theoretical discussion of this, few empirical data exist. The authors have determined the extent of LD among 38 biallelic markers with minor allele frequencies >.1, since these are most comparable to the common disease-susceptibility polymorphisms that association studies aim to detect. The markers come from three chromosomal regions-1,335 kb on chromosome 13q12-13, 380 kb on chromosome 19q13.2, and 120 kb on chromosome 22q13.3-which have been extensively mapped. These markers were examined in similar to1,600 individuals from four populations, all of European origin but with different demographic histories; Afrikaners, Ashkenazim, Finns, and East Anglian British. There are few differences, either in allele frequencies or in LD, among the populations studied. A similar inverse relationship was found between LD and distance in each genomic region and in each population. Mean D' is .68 for marker pairs 500 kb. However, only 50% of marker pairs at distances .3) to be useful in association studies. Results of the present study, if representative of the whole genome, suggest that a whole-genome scan searching for common disease-susceptibility alleles would require markers spaced less than or equal to5 kb apart.