Submitted on October 31, 2007
Accepted on January 2, 2008
Sequence Variants in the RNF212 Gene Associate with Genomewide Recombination Rate
Augustine Kong 1*, Gudmar Thorleifsson 1, Hreinn Stefansson 1, Gisli Masson 1, Agnar Helgason 1, Daniel F. Gudbjartsson 1, Gudrun M. Jonsdottir 1, Sigurjon A. Gudjonsson 1, Sverrir Sverrisson 1, Theodora Thorlacius 1, Aslaug Jonasdottir 1, Gudmundur A. Hardarson 1, Stefan T. Palsson 1, Michael L. Frigge 1, Jeffrey R. Gulcher 1, Unnur Thorsteinsdottir 1, Kari Stefansson 1*
1 deCODE Genetics Inc, 101 Reykjavik, Iceland.
* To whom correspondence should be addressed.
Augustine Kong , E-mail: kong{at}decode.is
Kari Stefansson , E-mail: kstefans{at}decode.is
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. Interestingly, the haplotype formed by two single-nucleotide polymorphisms (SNPs) associated with the highest recombination rate in males is associated with 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.
