Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology.
Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology.
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DOI：
10.1186/2047-217x-3-34
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发表时间：
2014
期刊：
影响因子：
9.2
通讯作者：
Xu X
中科院分区：
文献类型：
--
作者：
Cao H;Hastie AR;Cao D;Lam ET;Sun Y;Huang H;Liu X;Lin L;Andrews W;Chan S;Huang S;Tong X;Requa M;Anantharaman T;Krogh A;Yang H;Cao H;Xu X
结构变异（SV）在人群中比单核苷酸多态性和插入缺失更不常见，但共同占遗传多态性和疾病的很大一部分。由SV引起的碱基对差异比点突变高得多（>100倍）;然而，目前的检测方法都不全面，并且目前可用的方法无法提供足够的分辨率和跨越人类基因组中复杂区域的明确信息。为了应对这些挑战，我们应用了高通量、具有成本效益的基因组作图技术，以全球方式使用长单分子（>150 kb）全面发现全基因组SV并表征YH基因组的复杂区域。利用基于纳米通道的基因组定位技术，我们获得了708个插入/缺失和17个大于1 kb的倒位。排除与参考组装hg 19中的N-碱基空位重叠的59个SV（54个插入/缺失，5个倒位），剩余666个非空位SV，并且其中396个（60%）通过来自基于全基因组测序的重测序的配对末端数据或来自fosmid数据的从头组装序列验证。在剩余的270个SV中，260个是插入，213个与基因组变体数据库中的已知SV重叠。总体而言，666个变异中有609个（90%）得到了实验正交方法或公共数据库中历史证据的支持。与此同时，基因组作图也以简单的方式为具有单倍型的复杂区域提供了有价值的信息。此外，利用长的单分子标记模式，在全基因组规模上绘制了外源病毒序列，并在新的水平上分析了样品异质性。我们的研究强调了基因组作图技术作为一种全面和具有成本效益的方法，用于检测结构变异和研究人类基因组中的复杂区域，以及破译病毒整合到宿主基因组中。本文的在线版本（doi：10.1186/2047- 217 X-3-34）包含补充材料，可供授权用户使用。
Structural variants (SVs) are less common than single nucleotide polymorphisms and indels in the population, but collectively account for a significant fraction of genetic polymorphism and diseases. Base pair differences arising from SVs are on a much higher order (>100 fold) than point mutations; however, none of the current detection methods are comprehensive, and currently available methodologies are incapable of providing sufficient resolution and unambiguous information across complex regions in the human genome. To address these challenges, we applied a high-throughput, cost-effective genome mapping technology to comprehensively discover genome-wide SVs and characterize complex regions of the YH genome using long single molecules (>150 kb) in a global fashion. Utilizing nanochannel-based genome mapping technology, we obtained 708 insertions/deletions and 17 inversions larger than 1 kb. Excluding the 59 SVs (54 insertions/deletions, 5 inversions) that overlap with N-base gaps in the reference assembly hg19, 666 non-gap SVs remained, and 396 of them (60%) were verified by paired-end data from whole-genome sequencing-based re-sequencing or de novo assembly sequence from fosmid data. Of the remaining 270 SVs, 260 are insertions and 213 overlap known SVs in the Database of Genomic Variants. Overall, 609 out of 666 (90%) variants were supported by experimental orthogonal methods or historical evidence in public databases. At the same time, genome mapping also provides valuable information for complex regions with haplotypes in a straightforward fashion. In addition, with long single-molecule labeling patterns, exogenous viral sequences were mapped on a whole-genome scale, and sample heterogeneity was analyzed at a new level. Our study highlights genome mapping technology as a comprehensive and cost-effective method for detecting structural variation and studying complex regions in the human genome, as well as deciphering viral integration into the host genome. The online version of this article (doi:10.1186/2047-217X-3-34) contains supplementary material, which is available to authorized users.