Preferential occurrence of 1-2 microindels.
Preferential occurrence of 1-2 microindels.
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优先出现 1-2 个微插入缺失。
DOI：
10.1002/humu.20260
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发表时间：
2006
期刊：
影响因子：
3.9
通讯作者：
Sommer,SteveS
中科院分区：
文献类型：
--
作者：
Hill,KathleenA;Gonzalez,KellyD;Scaringe,WilliamA;Wang,Ji-Cheng;Sommer,SteveS
微插入缺失是独特的、不常见的突变，其导致在相同核苷酸位置处插入和缺失不同大小（在1个和50个核苷酸之间）的序列。对于导致这些突变的突变机制知之甚少。从我们在Big Blue®小鼠中的lacI基因中的6，016个独立体细胞突变事件的数据库中，我们组装了30个微插入缺失（0.5%）用于分析。具有一个核苷酸插入和两个核苷酸缺失（1-2个微插入缺失）的微插入缺失占观察到的微插入缺失的7个（23%），其余的微插入缺失分布在21种插入和缺失大小的其他组合中。在人类基因突变数据库（HGMD）中的人种系传播的突变中也观察到1-2个微插入缺失（20%）的优先发生。对小鼠1-2个微插入缺失侧翼序列的检查没有揭示明显的位点特异性或相关的二级结构。对1-2个微插入缺失的详细检查没有揭示纯微插入和微缺失事件的典型特征，而是提出了独特的突变机制。1-2个微插入中的1个碱基对插入和纯1个碱基对插入显示出不同的特征。1-2个微插入缺失的机制显然不是单纯的微插入和微缺失事件的简单组合。1-2个微插入缺失的显著增强需要解释。我们推测，某些易出错的聚合酶可能是体细胞组织和生殖细胞中优先出现1-2个微插入缺失的原因。据估计，一个成年人携带大约4000亿个体细胞1-2个微插入缺失，具有患癌症的可能性。《Mutat》27（1），55-61，2006年。© 2005 Wiley‐利斯公司
Microindels are unique, infrequent mutations that result in inserted and deleted sequences of different sizes (between one and 50 nucleotides) at the same nucleotide position. Little is known about the mutational mechanisms that are responsible for these mutations. From our database of 6,016 independent somatic mutational events in thelacIgene in Big Blue®mice, we assembled the 30 microindels (0.5%) for analysis. Microindels with one nucleotide inserted and two nucleotides deleted (1–2 microindels) accounted for seven (23%) of the microindels observed, with the remaining microindels distributed among 21 other combinations of insertion and deletion sizes. A preferential occurrence of 1–2 microindels (20%) was also observed in human germline transmitted mutations in the Human Gene Mutation Database (HGMD). An examination of the sequence flanking the mouse 1–2 microindels did not reveal obvious site specificity or associated secondary structure. A detailed examination of 1–2 microindels did not reveal the features typical of pure microinsertion and microdeletion events, but rather suggested a unique mutational mechanism. The 1 bp insertion in 1–2 microinsertions, and pure 1 bp insertions show distinct features. The mechanism for 1–2 microindels is not obviously a simple combination of pure microinsertion and microdeletion events. The dramatic enhancement of 1–2 microindels requires explanation. We speculate that certain error‐prone polymerases may be responsible for the preferential occurrence of 1–2 microindels in both somatic tissues and germ cells. It is estimated that a human adult carries roughly 400 billion somatic 1–2 microindels with the potential to predispose to cancer. Hum Mutat 27(1), 55–61, 2006. © 2005 Wiley‐Liss, Inc.