Rearrangement structure-independent strategy of CNV breakpoint analysis
Rearrangement structure-independent strategy of CNV breakpoint analysis
复制标题
CNV断点分析的重排结构独立策略
DOI：
10.1007/s00438-014-0850-4
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Zhang, Feng (张锋)
中科院分区：
文献类型：
--
作者：
Xu, Xiangmin;Xu, Xiangmin;Zhang, Feng (张锋);Zhang, Feng (张锋)
由人类基因组重排产生的罕见拷贝数变异（CNVs）在人类疾病和癌症的发病机制中起着重要作用。CNV断裂点分析可以帮助确定致病性CNV的基因组定位、遗传内容和序列结构。这一过程对于阐明CNV突变机制和CNV相关疾病的病因学至关重要。然而，在碱基对水平上定位CNV断裂点在技术上具有挑战性，特别是在具有序列复杂性的基因组区域。在本研究中，我们发展了一种新的捕获和断点接近测序（CBAS）的方法，以有效地获得CNV断点序列。该策略独立于CNV结构，适用于各种CNV类型。正如在CNV相关神经系统疾病患者中所证明的那样，CBAS实现了对复合缺失、复杂复制和易位的断点序列的精细定位。有趣的是，CBAS还揭示了意想不到的涉及长距离DNA重排的CNV复杂性。我们的观察表明，CBAS是一种获得CNV断裂点序列和定位插入事件的有效方法。该方法可为CNV相关疾病和癌症的研究提供便利。CBAS也适用于模式生物中逆转录病毒（如HIV）和转基因整合位点的定位。
Rare copy number variations (CNVs) generated by human genomic rearrangements have been shown to play an important role in pathogenesis of human diseases and cancers. CNV breakpoint analysis can help define genomic location, genetic content and sequence structure of pathogenic CNVs. This process is vital to elucidate CNV mutational mechanism and etiology of CNV-associated disorders. However, it is technically challenging to map CNV breakpoints at base-pair level, especially in the genomic regions with sequence complexity. In this study, we developed a new method ofcapture andbreakpointapproachingsequencing (CBAS) to efficiently obtain CNV breakpoint sequences. This strategy is independent of CNV structures and applicable to various CNV types. As was demonstrated in CNV-associated patients with neurological disorders, CBAS achieved fine mapping of breakpoint sequences for compound deletion, complex duplication, and translocation. Intriguingly, CBAS also revealed unexpected CNV complexity involving long-range DNA rearrangement. Our observations showed that CBAS is an efficient method for obtaining CNV breakpoint sequence and mapping insertional events as well. This method can facilitate the researches on CNV-associated human diseases and cancers. CBAS is also applicable to mapping the integration sites of retrovirus (such as HIV) and transgenes in model organisms.
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