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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Gene Rearrangement
  • Genetic Variation / genetics*
  • Genome, Human
  • Genomic Instability*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Homozygote
  • Humans
  • Male
  • Meiosis / genetics*
  • Mice
  • Molecular Sequence Data
  • Recombination, Genetic / genetics*
  • Spermatozoa


  • Histone-Lysine N-Methyltransferase
  • PRDM9 protein, human

Associated data

  • GENBANK/HM210983
  • GENBANK/HM210984
  • GENBANK/HM210985
  • GENBANK/HM210986
  • GENBANK/HM210987
  • GENBANK/HM210988
  • GENBANK/HM210989
  • GENBANK/HM210990
  • GENBANK/HM210991
  • GENBANK/HM210992
  • GENBANK/HM210993
  • GENBANK/HM210994
  • GENBANK/HM210995
  • GENBANK/HM210996
  • GENBANK/HM210997
  • GENBANK/HM210998
  • GENBANK/HM210999
  • GENBANK/HM211000
  • GENBANK/HM211001
  • GENBANK/HM211002
  • GENBANK/HM211003
  • GENBANK/HM211004
  • GENBANK/HM211005
  • GENBANK/HM211006