1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. [2] Centro de Pesquisas René Rachou-FIOCRUZ, Belo Horizonte, Brazil.
Nat Genet. 2013 Nov;45(11):1319-26. doi: 10.1038/ng.2768. Epub 2013 Sep 22.
We investigated 67 breakpoint junctions of gene copy number gains in 31 unrelated subjects. We observed a strikingly high frequency of small deletions and insertions (29%) apparently originating from polymerase slippage events, in addition to frameshifts and point mutations in homonucleotide runs (13%), at or flanking the breakpoint junctions of complex copy number variants. These single-nucleotide variants were generated concomitantly with the de novo complex genomic rearrangement (CGR) event. Our findings implicate low-fidelity, error-prone DNA polymerase activity in synthesis associated with DNA repair mechanisms as the cause of local increase in point mutation burden associated with human CGR.
我们研究了 31 个无关个体中基因拷贝数增益的 67 个断点连接，发现除了复杂拷贝数变异断点连接处的移码和点突变（13%）外，还存在大量明显来源于聚合酶滑动事件的小片段缺失和插入（29%）。这些单核苷酸变异是与从头发生的复杂基因组重排（CGR）事件同时产生的。我们的研究结果表明，与 DNA 修复机制相关的 DNA 合成过程中存在低保真度、易错 DNA 聚合酶活性，这可能是导致人类 CGR 相关点突变负担增加的原因。
