RNF212基因中的序列变异与全基因组重组率相关。

Sequence variants in the RNF212 gene associate with genome-wide recombination rate.

作者信息

Kong Augustine, Thorleifsson Gudmar, Stefansson Hreinn, Masson Gisli, Helgason Agnar, Gudbjartsson Daniel F, Jonsdottir Gudrun M, Gudjonsson Sigurjon A, Sverrisson Sverrir, Thorlacius Theodora, Jonasdottir Aslaug, Hardarson Gudmundur A, Palsson Stefan T, Frigge Michael L, Gulcher Jeffrey R, Thorsteinsdottir Unnur, Stefansson Kari

机构信息

deCODE Genetics Inc, 101 Reykjavik, Iceland.

出版信息

Science. 2008 Mar 7;319(5868):1398-401. doi: 10.1126/science.1152422. Epub 2008 Jan 31.

DOI:10.1126/science.1152422

PMID:18239089

Abstract

The genome-wide recombination rate varies between individuals, but the mechanism controlling this variation in humans has remained elusive. A genome-wide search identified sequence variants in the 4p16.3 region correlated with recombination rate in both males and females. These variants are located in the RNF212 gene, a putative ortholog of the ZHP-3 gene that is essential for recombinations and chiasma formation in Caenorhabditis elegans. It is noteworthy that the haplotype formed by two single-nucleotide polymorphisms (SNPs) associated with the highest recombination rate in males is associated with a low recombination rate in females. Consequently, if the frequency of the haplotype changes, the average recombination rate will increase for one sex and decrease for the other, but the sex-averaged recombination rate of the population can stay relatively constant.

摘要

全基因组重组率在个体之间存在差异，但控制人类这种差异的机制一直难以捉摸。一项全基因组搜索在4p16.3区域鉴定出与男性和女性重组率相关的序列变异。这些变异位于RNF212基因中，该基因是秀丽隐杆线虫中对重组和交叉形成至关重要的ZHP-3基因的假定直系同源基因。值得注意的是，由与男性最高重组率相关的两个单核苷酸多态性（SNP）形成的单倍型与女性的低重组率相关。因此，如果单倍型的频率发生变化，一种性别的平均重组率将增加，而另一种性别的平均重组率将降低，但群体的性别平均重组率可以保持相对恒定。