Kruglyak L
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Nat Genet. 1999 Jun;22(2):139-44. doi: 10.1038/9642.
Recently, attention has focused on the use of whole-genome linkage disequilibrium (LD) studies to map common disease genes. Such studies would employ a dense map of single nucleotide polymorphisms (SNPs) to detect association between a marker and disease. Construction of SNP maps is currently underway. An essential issue yet to be settled is the required marker density of such maps. Here, I use population simulations to estimate the extent of LD surrounding common gene variants in the general human population as well as in isolated populations. Two main conclusions emerge from these investigations. First, a useful level of LD is unlikely to extend beyond an average distance of roughly 3 kb in the general population, which implies that approximately 500,000 SNPs will be required for whole-genome studies. Second, the extent of LD is similar in isolated populations unless the founding bottleneck is very narrow or the frequency of the variant is low (<5%).
最近,注意力集中在利用全基因组连锁不平衡(LD)研究来定位常见疾病基因。此类研究将使用单核苷酸多态性(SNP)的密集图谱来检测标记与疾病之间的关联。SNP图谱的构建目前正在进行中。一个尚未解决的关键问题是此类图谱所需的标记密度。在此,我利用群体模拟来估计一般人群以及隔离人群中常见基因变异周围的LD程度。这些研究得出了两个主要结论。首先,在一般人群中,有用的LD水平不太可能延伸超过大约3 kb的平均距离,这意味着全基因组研究大约需要50万个SNP。其次,除非奠基瓶颈非常狭窄或变异频率很低(<5%),否则隔离人群中的LD程度是相似的。