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

Kong, Augustine; Thorleifsson, Gudmar; Stefansson, Hreinn; Masson, Gisli; Helgason, Agnar; Gudbjartsson, Daniel F; Jonsdottir, Gudrun M; Gudjonsson, Sigurjon A et al. · Science · 2008

basic_science · Level V

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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.

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