Evidence of DNA methylation in the neurofibromatosis type 1 (NF1) gene region of 17q11.2.
Evidence of DNA methylation in the neurofibromatosis type 1 (NF1) gene region of 17q11.2.
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DOI：
10.1093/hmg/2.4.439
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发表时间：
1993-04
影响因子：
3.5
通讯作者：
D. Rodenhiser;M. Coulter-Mackie;S. Singh
中科院分区：
文献类型：
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作者：
D. Rodenhiser;M. Coulter-Mackie;S. Singh
通过CpG二核苷酸中胞嘧啶的甲基化修饰哺乳动物DNA是涉及许多细胞和发育过程的复杂现象。特别地，CpG的特征性超突变性可能是导致人类遗传疾病的点突变的主要贡献者。我们假设DNA甲基化导致基因突变，导致1型神经纤维瘤病（NF 1），这是人类最常见的遗传疾病之一，并且是一种疾病，其中高达一半的病例是散发性生殖系突变的结果，通常在父系来源的等位基因中。我们使用了两种实验方法来分析NF 1基因区域CpG二核苷酸的DNA甲基化模式。Southern分析使用isotheromeric限制对揭示了DNA甲基化的区域侧翼的NF 1基因区域，而PCR甲基化分析表明，甲基化发生在基因组序列侧翼的NF 1基因和基因本身的编码区。我们认为，甲基化的CpG二核苷酸内和周围的高度突变的NF 1基因作为一个水库内的C->T转换有助于与疾病相关的自发性种系突变的高频率。
Modification of mammalian DNA by the methylation of cytosine in CpG dinucleotides is a complex phenomenon involved in a number of cellular and developmental processes. In particular, the characteristic hypermutability of CpGs may be a major contributor of point mutations leading to human genetic disease. We have hypothesized that DNA methylation contributes to mutations in the gene causing neurofibromatosis type 1 (NF1), one of the most common genetic disorders in humans and a disease where up to half of all cases are the result of sporadic germline mutations, usually in the paternally-derived allele. We have used two experimental approaches to analyze patterns of DNA methylation at CpG dinucleotides in the NF1 gene region. Southern analyses using isoschizomeric restriction pairs have revealed DNA methylation in areas flanking the NF1 gene region, while PCR-methylation assays have shown that methylation occurs both on genomic sequences flanking the NF1 gene and within the coding region of the gene itself. We suggest that methylated CpG dinucleotides within and around the highly mutable NF1 gene serve as a reservoir within which C-->T transitions contribute to the high frequency of spontaneous germline mutations associated with the disease.