The fine-scale structure of recombination rate variation in the human genome
The fine-scale structure of recombination rate variation in the human genome
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DOI：
10.1126/science.1092500
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发表时间：
2004-04-23
期刊：
影响因子：
56.9
通讯作者：
Donnelly, P
中科院分区：
文献类型：
--
作者：
McVean, GAT;Myers, SR;Donnelly, P
对于大多数物种而言，重组率变异的性质和规模在很大程度上是未知的。在人类中，家系分析记录了染色体水平的变异，精子研究已经确定了交叉事件聚集的特定热点。为了探讨这种情况是否代表整个基因组，我们开发并验证了一种从遗传变异模式估算重组率的方法。从对欧洲和非洲人群进行的广泛的单核苷酸多态性调查中，我们发现了局部重组率极端变异的证据，其幅度跨越四个数量级，其中50%的重组事件发生在不到10%的序列中。我们证明重组热点是人类基因组的一个普遍特征，平均每200千碱基或更短的距离就会出现，但重组优先发生在基因之外。
The nature and scale of recombination rate variation are largely unknown for most species. In humans, pedigree analysis has documented variation at the chromosomal level, and sperm studies have identified specific hotspots in which crossing-over events cluster. To address whether this picture is representative of the genome as a whole, we have developed and validated a method for estimating recombination rates from patterns of genetic variation. From extensive single-nucleotide polymorphism surveys in European and African populations, we find evidence for extreme local rate variation spanning four orders in magnitude, in which 50% of all recombination events take place in less than 10% of the sequence. We demonstrate that recombination hotspots are a ubiquitous feature of the human genome, occurring on average every 200 kilobases or less, but recombination occurs preferentially outside genes.