Characterization of 26 deletion CNVs reveals the frequent occurrence of micro-mutations within the breakpoint-flanking regions and frequent repair of double-strand breaks by templated insertions derived from remote genomic regions
Characterization of 26 deletion CNVs reveals the frequent occurrence of micro-mutations within the breakpoint-flanking regions and frequent repair of double-strand breaks by templated insertions derived from remote genomic regions
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26 个缺失 CNV 的表征揭示了断点侧翼区域内频繁发生微突变，以及通过源自远程基因组区域的模板化插入频繁修复双链断裂
DOI：
10.1007/s00439-015-1539-4
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发表时间：
2015-03
期刊：
影响因子：
5.3
通讯作者：
Yiming Wang
中科院分区：
文献类型：
--
作者：
Ye Wang;Peiqiang Su;Bin Hu;Wenjuan Zhu;Qibin Li;Ping Yuan;Jiangchao Li;Xinyuan Guan;Fucheng Li;Xiangyi Jing;Ru Li;Yongling Zhang;Claude Ferec;David N.Cooper;Jun Wang;Dongsheng Huang;Jian-Min Chen;Yiming Wang
据报道，越来越多的拷贝数变化（CNV）引起或易感人类疾病。但是，这些CNV中的很大一部分尚未在单基本对水平上进行准确的表征，从而阻碍了对CNV形成的突变机制的更好理解。 Here, employing a composite pipeline method derived from various inference-based programs, we have characterized 26 deletion CNVs [including three novel pathogenic CNVs involving an autosomal gene (EXT2) causing hereditary osteochondromas and an X-linked gene (CLCN5) causing Dent disease, as well as 23 CNVs previously identified by inference from a cohort of Canadian autism spectrum disorder [族]从全基因组测序数据中达到单基准对准确性的水平。我们发现，删除CNV的显着部分（5/26; 19％）中存在断点 - 持平的微突变（在断点的22 bp之内）。该分析还提供了证据表明，最近描述的DNA修复形式（即，通过模板的核苷酸序列插入源自基因组的遥远区域的模板核苷酸序列插入）不仅会导致人类遗传疾病，还会影响人类基因组进化。我们的发现说明了精确的CNV断点描述对于理解潜在的突变机制的重要性，并且对引物设计在临床诊断中检测缺失CNV的意义具有影响。
Copy number variations (CNVs) have increasingly been reported to cause, or predispose to, human disease. However, a large fraction of these CNVs have not been accurately characterized at the single-base-pair level, thereby hampering a better understanding of the mutational mechanisms underlying CNV formation. Here, employing a composite pipeline method derived from various inference-based programs, we have characterized 26 deletion CNVs [including three novel pathogenic CNVs involving an autosomal gene (EXT2) causing hereditary osteochondromas and an X-linked gene (CLCN5) causing Dent disease, as well as 23 CNVs previously identified by inference from a cohort of Canadian autism spectrum disorder families] to the single-base-pair level of accuracy from whole-genome sequencing data. We found that breakpoint-flanking micro-mutations (within 22 bp of the breakpoint) are present in a significant fraction (5/26; 19 %) of the deletion CNVs. This analysis also provided evidence that a recently described error-prone form of DNA repair (i.e., repair of DNA double-strand breaks by templated nucleotide sequence insertions derived from distant regions of the genome) not only causes human genetic disease but also impacts on human genome evolution. Our findings illustrate the importance of precise CNV breakpoint delineation for understanding the underlying mutational mechanisms and have implications for primer design in relation to the detection of deletion CNVs in clinical diagnosis.
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DOI：
10.1016/j.tig.2008.08.007
发表时间：
2008-11
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
McVey M;Lee SE
通讯作者：
Lee SE
影响因子：
8.8
作者：
Shah KA;Shishkin AA;Voineagu I;Pavlov YI;Shcherbakova PV;Mirkin SM
通讯作者：
Mirkin SM
影响因子：
64.8
作者：
Keskin H;Shen Y;Huang F;Patel M;Yang T;Ashley K;Mazin AV;Storici F
通讯作者：
Storici F
DOI：
--
发表时间：
2008
期刊：
--
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.9
作者：
Shengfeng Huang;Ting Yu;Zelin Chen;Shaochun Yuan;Shangwu Chen;A. Xu
通讯作者：
Shengfeng Huang;Ting Yu;Zelin Chen;Shaochun Yuan;Shangwu Chen;A. Xu