Distinct patterns of germ-line deletions in MLH1 and MSH2: the implication of Alu repetitive element in the genetic etiology of Lynch syndrome (HNPCC).
Distinct patterns of germ-line deletions in MLH1 and MSH2: the implication of Alu repetitive element in the genetic etiology of Lynch syndrome (HNPCC).
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DOI：
10.1002/humu.9417
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发表时间：
2006-04-01
期刊：
影响因子：
3.9
通讯作者：
Foulkes, William D
中科院分区：
文献类型：
--
作者：
Li, Lili;McVety, Susan;Foulkes, William D
在来自不同种族的Lynch综合征(HNPCC)患者中，MLH1和MSH2的生殖系基因组重排的频率相对较高。为了研究潜在的分子机制，我们描述了11个生殖系缺失的DNA断裂点，其中6个是MLH1，5个是MSH2。发现这两个基因的缺失模式截然不同。这5例MSH2缺失完全是由重复的Alu序列介导的基因内不平等重组所致。相反，6个MLH1缺失中有5个是由于没有显著同源性的序列重组所致(P=0.015)。对这两个基因的DNA断裂点的详细分析证实，Alu介导的不平等重组是MSH2(n=34)的主要缺失类型，而MLH1(n=21)不是(P
A relatively high frequency of germ-line genomic rearrangements in MLH1 and MSH2 has been reported among Lynch Syndrome (HNPCC) patients from different ethnic populations. To investigate the underlying molecular mechanisms, we characterized the DNA breakpoints of 11 germ-line deletions, six for MLH1 and five for MSH2. Distinct deletion patterns were found for the two genes. The five cases of MSH2 deletions result exclusively from intragenic unequal recombination mediated by repetitive Alu sequences. In contrast, five out of the six MLH1 deletions are due to recombinations involving sequences of no significant homology (P=0.015). A detailed analysis of the DNA breakpoints in the two genes, previously characterized by other groups, validated the observation that Alu-mediated unequal recombination is the main type of deletion in MSH2 (n=34), but not in MLH1 (n=21) (P