PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans..pdf (1.28 MB)
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PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.

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journal contribution
posted on 24.10.2012, 09:11 by Ingrid L. Berg, Rita Neumann, Kwan-Wood G. Lam, Shriparna Sarbajna, Linda Odenthal-Hesse, Celia A. May, Alec J. Jeffreys
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.

History

Citation

Nature Genetics, 2010, 42 (10), pp. 859-863

Version

AM (Accepted Manuscript)

Published in

Nature Genetics

Publisher

Nature Publishing Group

issn

1061-4036

eissn

1546-1718

Copyright date

2010

Available date

24/10/2012

Publisher version

http://www.nature.com/ng/journal/v42/n10/full/ng.658.html

Language

eng