Genomic and geographic distribution of SNP-defined runs of homozygosity in Europeans
Genomic and geographic distribution of SNP-defined runs of homozygosity in Europeans
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DOI：
10.1093/hmg/ddq198
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发表时间：
2010-08-01
影响因子：
3.5
通讯作者：
Krawczak, Michael
中科院分区：
文献类型：
--
作者：
Nothnagel, Michael;Lu, Timothy Tehua;Krawczak, Michael
高密度遗传多态仪表板的可获得性导致在人类基因组中发现了明显自合子的扩展区域。在基因水平上，这些区域表现为相当大的纯合子(ROH)延伸或“游程”。在这里，我们调查了来自23个亚群的大量欧洲个体样本中RoHS的基因组和地理分布。基因组ROH分布的特征是高度显著的不均匀模式，在所有研究的亚群中几乎是相同的。大约77个染色体区域以相当高的频率含有RoHS，从而形成了不能仅用高连锁不平衡来解释的‘ROH岛’。在地理层面上，RoHS的数量和累积长度遵循从南到北的显著梯度，符合欧洲人口历史的预期。相比之下，个体的ROH长度只显示出微小的和非系统的地理差异。虽然我们的发现与南欧比北欧更大的有效种群规模相一致，再加上历史上更高的人口密度和流动性，但它们也表明，整个欧洲大陆的人类减数分裂重组模式肯定非常相似。我们的数据延续了之前关于地理和国家身份之间强烈关联的报告，我们的数据显示，欧洲人按血统划分的基因组身份模式也是克隆式的。因此，基于ROH的基因研究的规划、设计和解释必须考虑样本来源，以便这些研究是合理和有效的。
The availability of high-density panels of genetic polymorphisms has led to the discovery of extended regions of apparent autozygosity in the human genome. At the genotype level, these regions present as sizeable stretches, or 'runs', of homozygosity (ROH). Here, we investigated both the genomic and the geographic distribution of ROHs in a large European sample of individuals originating from 23 subpopulations. The genomic ROH distribution was found to be characterized by a pattern of highly significant non-uniformity that was virtually identical in all subpopulations studied. Some 77 chromosomal regions contained ROHs at considerable frequency, thereby forming 'ROH islands' that were not explicable by high linkage disequilibrium alone. At the geographic level, the number and cumulative length of ROHs followed a prominent South to North gradient in agreement with expectations from European population history. The individual ROH length, in contrast, showed only minor and unsystematic geographic variation. While our findings are thus consistent with a larger effective population size in Southern than in Northern Europe, combined with a higher historic population density and mobility, they also indicate that the patterns of meiotic recombination in humans must have been very similar throughout the continent. Extending previous reports of a strong correlation between geography and identity-by-state, our data show that the genomic identity-by-descent patterns of Europeans are also clinal. As a consequence, the planning, design and interpretation of ROH-based genetic studies must take sample origin into account in order for such studies to be sensible and valid.