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Unequal homologous recombination between LINE-1 elements as a mutational mechanism in human genetic disease

机译:LINE-1元件之间的不平等同源重组是人类遗传疾病的突变机制

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Unequal homologous recombination between repetitive genetic elements is one mechanism that mediates genome instability. We have characterized a homologous recombination event between two neighboring LINE-1 sequences in the human gene encoding the beta subunit of phosphorylase kinase (PHKB). It has lead to the deletion of 7574 nucleotides of genomic DNA including exon 8 of tl-Lis gene, giving rise to glycogen storage disease through phosphorylase kinase deficiency. To our knowledge, this is the first example of a mutation due to unequal homologous recombination between LINE-1 elements. The sequence features of tie recombining LINE-1 elements and of the recombination junction site, and possible reasons for the more frequent occurrence of unequal homologous recombination between Aln elements are discussed. (C) 1998 Academic Press Limited. [References: 34]
机译:重复遗传元件之间的不平等同源重组是介导基因组不稳定的一种机制。我们已经表征了人类基因中编码磷酸化酶激酶(PHKB)的β亚基的两个相邻的LINE-1序列之间的同源重组事件。它已导致基因组DNA的7574个核苷酸的缺失,包括tl-Lis基因的外显子8,通过磷酸化酶激酶的缺乏引起糖原贮积病。据我们所知,这是由于LINE-1元件之间的同源重组不平等而引起的突变的第一个例子。讨论了领带重组LINE-1元件和重组连接位点的序列特征,以及Aln元件之间更频繁发生不均等同源重组的可能原因。 (C)1998 Academic Press Limited。 [参考:34]

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