Genomic Patterns of Homozygosity in Worldwide Human Populations
Genomic Patterns of Homozygosity in Worldwide Human Populations
复制标题
DOI：
10.1016/j.ajhg.2012.06.014
复制
发表时间：
2012-08-10
影响因子：
9.8
通讯作者：
Li, Jun Z.
中科院分区：
文献类型：
--
作者：
Pemberton, Trevor J.;Absher, Devin;Li, Jun Z.
全基因组范围内的纯合性运行模式和它们在个体之间的变异为研究人类遗传多样性和进化历史提供了一个宝贵的和经常未开发的资源。使用577，489个常染色体SNP的基因型数据，我们采用基于似然性的方法来识别代表64个全球人群的1，839个个体的纯合性（ROH），并使用基于模型的聚类算法将其按长度分为三类-短，中，长。对于每个类，每个个体的ROH的数量和总长度在个体和群体之间显示出相当大的变化。每个人的短和中间ROH的总长度的增加与人口的距离从东非，在协议与以前观察到的基因座明智的纯合性和连锁不平衡类似的模式。相比之下，长ROH的总长度显示大的个体间的变化，可能反映了最近的近亲繁殖模式，较高的值更经常发生在人口中已知的高频率的近亲工会。在整个基因组中，ROH的分布并不均匀，并且具有独特的大陆模式。整个基因组的ROH频率与局部基因组变量（如重组率）以及最近的阳性选择信号相关。此外，长ROH更常见于携带常染色体显性遗传疾病相关基因的基因组区域中，而不是与孟德尔疾病无关的区域中。这些结果提供了对纯合性模式产生方式的深入了解，并且它们产生了基线纯合性模式，这些模式可用于辅助与隐性疾病相关的基因的纯合性作图。
Genome-wide patterns of homozygosity runs and their variation across individuals provide a valuable and often untapped resource for studying human genetic diversity and evolutionary history. Using genotype data at 577,489 autosomal SNPs, we employed a likelihood-based approach to identify runs of homozygosity (ROH) in 1,839 individuals representing 64 worldwide populations, classifying them by length into three classes-short, intermediate, and long-with a model-based clustering algorithm. For each class, the number and total length of ROH per individual show considerable variation across individuals and populations. The total lengths of short and intermediate ROH per individual increase with the distance of a population from East Africa, in agreement with similar patterns previously observed for locus-wise homozygosity and linkage disequilibrium. By contrast, total lengths of long ROH show large interindividual variations that probably reflect recent inbreeding patterns, with higher values occurring more often in populations with known high frequencies of consanguineous unions. Across the genome, distributions of ROH are not uniform, and they have distinctive continental patterns. ROH frequencies across the genome are correlated with local genomic variables such as recombination rate, as well as with signals of recent positive selection. In addition, long ROH are more frequent in genomic regions harboring genes associated with autosomal-dominant diseases than in regions not implicated in Mendelian diseases. These results provide insight into the way in which homozygosity patterns are produced, and they generate baseline homozygosity patterns that can be used to aid homozygosity mapping of genes associated with recessive diseases.