Variation in human recombination rates and its genetic determinants.
Variation in human recombination rates and its genetic determinants.
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DOI：
10.1371/journal.pone.0020321
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Przeworski M
中科院分区：
文献类型：
--
作者：
Fledel-Alon A;Leffler EM;Guan Y;Stephens M;Coop G;Przeworski M
尽管交换在人类减数分裂中染色体配对和分离中起着重要作用，但交换的速率和位置在个体之间差异很大。描述这种变异并确定其决定因素是我们理解人类重组过程及其演变的重要步骤。使用三大套欧美血统，我们研究了五个重组表型的变化，捕获不同方面的交换模式。我们发现，男性和女性的平均重组率和历史热点的使用是显着的遗传和彼此不相关。然后，我们进行了全基因组关联研究，以确定影响它们的基因座。我们复制了RNF212与男性和女性平均发病率的关联，以及倒位17q21.31与女性平均发病率的关联。我们还复制了PRDM9与历史热点使用的关联，发现它解释了这种表型中的大部分遗传变异。此外，我们确定了一组新的候选区域，以供进一步验证。这些研究结果表明，在广泛和精细尺度的变化在很大程度上是可分离的，除了三个已知的位点，没有证据表明常见的变异与重组表型的大的影响。
Despite the fundamental role of crossing-over in the pairing and segregation of chromosomes during human meiosis, the rates and placements of events vary markedly among individuals. Characterizing this variation and identifying its determinants are essential steps in our understanding of the human recombination process and its evolution. Using three large sets of European-American pedigrees, we examined variation in five recombination phenotypes that capture distinct aspects of crossing-over patterns. We found that the mean recombination rate in males and females and the historical hotspot usage are significantly heritable and are uncorrelated with one another. We then conducted a genome-wide association study in order to identify loci that influence them. We replicated associations of RNF212 with the mean rate in males and in females as well as the association of Inversion 17q21.31 with the female mean rate. We also replicated the association of PRDM9 with historical hotspot usage, finding that it explains most of the genetic variance in this phenotype. In addition, we identified a set of new candidate regions for further validation. These findings suggest that variation at broad and fine scales is largely separable and that, beyond three known loci, there is no evidence for common variation with large effects on recombination phenotypes.
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通讯作者：
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