A common sequence motif associated with recombination hot spots and genome instability in humans
A common sequence motif associated with recombination hot spots and genome instability in humans
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DOI：
10.1038/ng.213
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发表时间：
2008-09-01
期刊：
影响因子：
30.8
通讯作者：
McVean, Gil
中科院分区：
文献类型：
--
作者：
Myers, Simon;Freeman, Colin;McVean, Gil
在人类中，大多数减数分裂交叉事件聚集在基因组的短区域，称为重组热点。我们之前已经发现了富含热点的DNA基序，特别是7-mer CCTCCCT。在这里，我们使用Phase 2 HapMap提供的增加的热点分辨率和新颖的搜索方法来识别基于退化的13-mer CCNCCNTNNCCNC的扩展基序家族，这对于在至少40%的人类热点中招募交叉事件至关重要，并且在两性中具有不同的遗传背景。此外，这些基序在高变小卫星中被发现，并聚集在致病的非等位基因同源重组热点和常见的线粒体缺失热点的断点区域，暗示该基序是基因组不稳定的驱动因素。
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.