Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex
Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex
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DOI：
10.1038/ng1001-217
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发表时间：
2001-10-01
期刊：
影响因子：
30.8
通讯作者：
Neumann, R
中科院分区：
文献类型：
--
作者：
Jeffreys, AJ;Kauppi, L;Neumann, R
人们对了解人类基因组中的连锁不平衡(LD)模式非常感兴趣，以帮助研究人类进化并促进复杂疾病的关联研究(1-5)。然而，减数分裂交叉分布和种群历史对LD的相对影响尚不清楚(5)。特别是，它不确定在多大程度上交叉聚集到可能影响盖子图案的热点(6-8)。作为研究LD和重组关系的第一步，我们分析了主要组织相容性复合体(MHC)II类区域的一段216kb的片段，该片段已被表征为家族性交叉(9)。高分辨率LD分析表明，存在强缔合的扩展结构域，被LD击穿的拼接区域中断。精子鉴定显示，这些区域正好对应于减数分裂交叉热点。所定义的所有六个热点具有非常相似的对称形态，但强度有很大差异，并且与热点活性的任何主要DNA序列决定因素没有明显关联。这些热点以星系团的形式出现，共同构成了MHC这一区域的几乎所有交叉。这些数据表明，至少在MHC内部，交叉远远不是在分子水平上随机分布的，复合热点可以深刻地影响LD图案。
There is considerable interest in understanding patterns of linkage disequilibrium (LD) in the human genome, to aid investigations of human evolution and facilitate association studies in complex disease(1-5). The relative influences of meiotic crossover distribution and population history on LD remain unclear, however(5). In particular, it is uncertain to what extent crossovers are clustered into 'hot SpotS,(6-8) that might influence LID patterns. As a first step to investigating the relationship between LD and recombination, we have analyzed a 216-kb segment of the class II region of the major histocompatibility complex (MHC) already characterized for familial crossovers(9). High-resolution LD analysis shows the existence of extended domains of strong association interrupted by patchwork areas of LD breakdown. Sperm typing shows that these areas correspond precisely to meiotic crossover hot spots. All six hot spots defined share a remarkably similar symmetrical morphology but vary considerably in intensity, and are not obviously associated with any primary DNA sequence determinants of hot-spot activity. These hot spots occur in clusters and together account for almost all crossovers in this region of the MHC. These data show that, within the MHC at least, crossovers are far from randomly distributed at the molecular level and that recombination hot spots can profoundly affect LD patterns.