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

被引：238

作者：

Berg, Ingrid L. ^{[1
]}

Neumann, Rita ^{[1
]}

Lam, Kwan-Wood G. ^{[1
]}

Sarbajna, Shriparna ^{[1
]}

Odenthal-Hesse, Linda ^{[1
]}

May, Celia A. ^{[1
]}

Jeffreys, Alec J. ^{[1
]}

机构：

[1] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England

来源：

NATURE GENETICS | 2010年 / 42卷 / 10期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

CONSTITUTIONAL T(11/22); MINISATELLITE MUTATION; GERMLINE MUTATION; GENETIC-VARIATION; HUMAN GENOME; HOTSPOT; CROSSOVER; SPERM; POLYMORPHISM; FREQUENCY;

D O I：

10.1038/ng.658

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

PRDM9 has recently been identified as a likely trans regulator of meiotic recombination hot spots in humans and mice(1-3). PRDM9 contains a zinc finger array that, in humans, can recognize a short sequence motif associated with hot spots(4), with binding to this motif possibly triggering hot-spot activity via chromatin remodeling(5). 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(6) as well as minisatellite instability(7)-implicating PRDM9 as a risk factor for some pathological genome rearrangements.

引用

页码：859 / +

页数：6

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