A common sequence motif associated with recombination hot spots and genome instability in humans

被引：344

作者：

Myers, Simon ^{[1
,2
]}

Freeman, Colin ^{[2
]}

Auton, Adam ^{[2
,3
]}

Donnelly, Peter ^{[2
,4
]}

McVean, Gil ^{[2
]}

机构：

[1] Massachusetts Inst Technol & Harvard, Broad Inst, Cambridge, MA 02142 USA

[2] Univ Oxford, Dept Stat, Oxford OX1 3TG, England

[3] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA

[4] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

来源：

NATURE GENETICS | 2008年 / 40卷 / 09期

基金：

英国工程与自然科学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1038/ng.213

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

In humans, most meiotic crossover events are clustered into short regions of the genome known as recombination hot spots. We have previously identified DNA motifs that are enriched in hot spots, particularly the 7-mer CCTCCCT. Here we use the increased hot-spot resolution afforded by the Phase 2 HapMap and novel search methods to identify an extended family of motifs based around the degenerate 13-mer CCNCCNTNNCCNC, which is critical in recruiting crossover events to at least 40% of all human hot spots and which operates on diverse genetic backgrounds in both sexes. Furthermore, these motifs are found in hypervariable minisatellites and are clustered in the breakpoint regions of both disease-causing nonallelic homologous recombination hot spots and common mitochondrial deletion hot spots, implicating the motif as a driver of genome instability.

引用

收藏

页码：1124 / 1129

页数：6

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