Intense and highly localized gene conversion activity in human meiotic crossover hot spots
Intense and highly localized gene conversion activity in human meiotic crossover hot spots
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DOI：
10.1038/ng1287
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发表时间：
2004-02-01
期刊：
影响因子：
30.8
通讯作者：
May, CA
中科院分区：
文献类型：
--
作者：
Jeffreys, AJ;May, CA
减数分裂基因转换在等位基因多样化以及基因和其他重复DNA序列家族的同质化中具有重要作用（1-5），有时具有病理后果（6，7）。但是对于人类基因转换的动力学及其与减数分裂交叉的关系知之甚少。因此，我们开发了筛选和选择方法，以表征主要组织相容性复合体（MHC）中两个减数分裂交叉热点（8）和性染色体假常染色体配对区PAR 1中的一个热点（参考文献9）中的精子转化。所有这三个热点都在基因转换和交叉中活跃。转换域是短的，并定义了一个陡峭的双向梯度中心的交叉活动的峰值，由相同的重组启动事件产生的交叉和转换一致。这些初始化似乎分布在一个狭窄的区域，而不是发生在一个单一的网站，似乎优先产生转换，而不是交叉。交叉断点比转换断点更广泛地扩散，这表明在起始后转换和交叉处理之间的差异或存在质量控制检查点，在该检查点处同源染色体之间的短相互作用优先中止为转换。
Meiotic gene conversion has an important role in allele diversification and in the homogenization of gene and other repeat DNA sequence families(1-5), sometimes with pathological consequences(6,7). But little is known about the dynamics of gene conversion in humans and its relationship to meiotic crossover. We therefore developed screening and selection methods to characterize sperm conversions in two meiotic crossover hot spots in the major histocompatibility complex (MHC)(8) and one in the sex chromosomal pseudoautosomal pairing region PAR1 (ref. 9). All three hot spots are active in gene conversion and crossover. Conversion tracts are short and define a steep bidirectional gradient centered at the peak of crossover activity, consistent with crossovers and conversions being produced by the same recombination-initiating events. These initiations seem to be spread over a narrow zone, rather than occurring at a single site, and seem preferentially to yield conversions rather than crossovers. Crossover breakpoints are more broadly diffused than conversion breakpoints, suggesting either differences between conversion and crossover processing after initiation or the existence of a quality control checkpoint at which short interactions between homologous chromosomes are preferentially aborted as conversions.