PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.
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.
Berg
Ingrid L
IL
Department of Genetics, University of Leicester, Leicester, UK.
Neumann
Rita
R
Lam
Kwan-Wood G
KW
Sarbajna
Shriparna
S
Odenthal-Hesse
Linda
L
May
Celia A
CA
Jeffreys
Alec J
AJ
D000483:Alleles; D000818:Animals; D015321:Gene Rearrangement; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human; D042822:Genomic Instability; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011995:Recombination, Genetic / Q000235:genetics*; D013094:Spermatozoa
D011495:Histone-Lysine N-Methyltransferase; C544431:PRDM9 protein, human
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