Recurrent DNA inversion rearrangements in the human genome
Recurrent DNA inversion rearrangements in the human genome
复制标题
DOI：
10.1073/pnas.0701631104
复制
发表时间：
2007-04-10
影响因子：
11.1
通讯作者：
Palacios, Rafael
中科院分区：
文献类型：
--
作者：
Flores, Margarita;Morales, Lucia;Palacios, Rafael
一些证据表明，人类基因组中的重复序列是非等位基因同源重组（NAHR）的靶点，这有助于基因组重排。我们已经使用基于PCR的方法来识别人类基因组中重排结构的断点区域。特别是，我们已经确定了位于反向方向的染色体内相同重复序列，这可能导致染色体倒位。开发了生物信息学工作流程路径，以选择适当的区域进行分析。研究人员分析了位于3号、15号和19号染色体上与已知人类基因重叠的三个区域。在来自不同无关个体的血液DNA样本中确定了野生型与重排结构的相对比例。所获得的结果表明，复发性基因组重排发生在相对较高的频率在体细胞。有趣的是，所研究的重排在成人中比在新生儿个体中显著更丰富，这表明这种DNA重排可能在胚胎发生或胎儿生命中开始出现，并在出生后继续积累。我们的研究结果在人类基因组变异的相关性进行了讨论。
Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome. In particular, we have identified intrachromosomal identical repeats that are located in reverse orientation, which may lead to chromosomal inversions. A bioinformatic workflow pathway to select appropriate regions for analysis was developed. Three such regions overlapping with known human genes, located on chromosomes 3,15, and 19, were analyzed. The relative proportion of wild-type to rearranged structures was determined in DNA samples from blood obtained from different, unrelated individuals. The results obtained indicate that recurrent genomic rearrangements occur at relatively high frequency in somatic cells. Interestingly, the rearrangements studied were significantly more abundant in adults than in newborn individuals, suggesting that such DNA rearrangements might start to appear during embryogenesis or fetal life and continue to accumulate after birth. The relevance of our results in regard to human genomic variation is discussed.