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Nat Genet. 2010 Oct;42(10):859-63. doi: 10.1038/ng.658. Epub 2010 Sep 5.

PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.

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1
Department of Genetics, University of Leicester, Leicester, UK.

Abstract

PRDM9 has recently been identified as a likely trans regulator of meiotic recombination hot spots in humans and mice. PRDM9 contains a zinc finger array that, in humans, can recognize a short sequence motif associated with hot spots, with binding to this motif possibly triggering hot-spot activity via chromatin remodeling. We now report that human genetic variation at the PRDM9 locus has a strong effect on sperm hot-spot activity, even at hot spots lacking the sequence motif. Subtle changes within the zinc finger array can create hot-spot nonactivating or enhancing variants and can even trigger the appearance of a new hot spot, suggesting that PRDM9 is a major global regulator of hot spots in humans. Variation at the PRDM9 locus also influences aspects of genome instability-specifically, a megabase-scale rearrangement underlying two genomic disorders as well as minisatellite instability-implicating PRDM9 as a risk factor for some pathological genome rearrangements.

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PMID:
20818382
PMCID:
PMC3092422
DOI:
10.1038/ng.658
[Indexed for MEDLINE]
Free PMC Article

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