Department of Human Genetics, The University of Chicago, Illinois, USA.
Genet Epidemiol. 2010 Feb;34(2):133-9. doi: 10.1002/gepi.20442.
Founder or isolated populations have advantages for genetic studies due to decreased genetic and environmental heterogeneity. However, whereas longer-range linkage disequilibrium (LD) in these populations is expected to facilitate gene localization, extensive LD may actually limit the ability for gene discovery. The North American Hutterite population is one of the best characterized young founder populations and members of this isolate have been the subjects of our studies of complex traits, including fertility, asthma and cardiovascular disease, for >20 years. Here, we directly assess the patterns and extent of global LD using single nucleotide polymorphism genotypes with minor allele frequencies (MAFs) > or =5% from the Affymetrix GeneChip Mapping 500 K array in 60 relatively unrelated Hutterites and 60 unrelated Europeans (HapMap CEU). Although LD among some marker pairs extends further in the Hutterites than in Europeans, the pattern of LD and MAF are surprisingly similar. These results indicate that (1) identifying disease genes should be no more difficult in the Hutterites than in outbred European populations, (2) the same common susceptibility alleles for complex diseases should be present in the Hutterites and outbred European populations, and (3) imputation algorithms based on HapMap CEU should be applicable to the Hutterites.
由于遗传和环境异质性降低，创始人群体或隔离群体在遗传研究方面具有优势。然而，这些群体中较长的连锁不平衡（LD）有望促进基因定位，但广泛的 LD 实际上可能限制基因发现的能力。北美哈特派群体是最具代表性的年轻创始人群体之一，该隔离群体的成员一直是我们研究复杂特征的对象，包括生育能力、哮喘和心血管疾病，已有超过 20 年的历史。在这里，我们直接使用来自 Affymetrix GeneChip Mapping 500 K 阵列的最小等位基因频率（MAF）> = 5%的单核苷酸多态性基因型，评估 60 个相对无关的哈特派人和 60 个无关的欧洲人（HapMap CEU）中的全球 LD 模式和程度。尽管一些标记对之间的 LD 在哈特派人中比在欧洲人中延伸得更远，但 LD 的模式和 MAF 非常相似。这些结果表明：（1）在哈特派人中识别疾病基因应该与在杂合欧洲人群中一样困难；（2）复杂疾病的相同常见易感等位基因应该存在于哈特派人和杂合欧洲人群中；（3）基于 HapMap CEU 的推断算法应该适用于哈特派人。
