Mobile elements create structural variation: Analysis of a complete human genome
Mobile elements create structural variation: Analysis of a complete human genome
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DOI：
10.1101/gr.091827.109
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发表时间：
2009-09-01
期刊：
影响因子：
7
通讯作者：
Jorde, Lynn B.
中科院分区：
文献类型：
--
作者：
Xing, Jinchuan;Zhang, Yuhua;Jorde, Lynn B.
结构变异（SVs）在人类基因组中很常见。因为大约一半的人类基因组是由重复的、转座的DNA序列组成的，所以这些元素在人类SVs的产生中起着重要作用是合理的。一个人的二倍体基因组测序（HuRef）为我们提供了第一次以彻底和公正的方式评估移动元件对个体SVs的影响的机会。在这项研究中，我们系统地评估了超过8000个SVs，以鉴定小至100 bp的HuRef基因组特异性移动元件相关SVs。结合计算和实验分析，我们鉴定并验证了706个移动元件插入事件（包括Alu， L1， SVA元件和非经典插入），与人类基因组计划（HGP）参考序列（hg18）相比，这些事件为HuRef基因组增加了超过305 kb的新DNA序列。我们还确定了140个与移动元素相关的删除，其中删除了；HuRef基因组126 kb的序列。总的来说,;大于100 bp的特定于huref的索引中有10%是由与移动元素相关的事件引起的。超过三分之一的插入/删除事件发生在基因区域，新的Alu插入发生在三个人类基因的外显子上。根据插入的数量和HuRef和HGP参考基因组到最近共同祖先的估计时间，我们估计Alu、L1和SVA的反转位率分别为1 / 21、212和916。该研究首次对个体完整DNA序列中与移动元件相关的结构变异进行了全面分析，并证明了移动元件在产生个体间结构变异中发挥了重要作用。
Structural variants (SVs) are common in the human genome. Because approximately half of the human genome consists of repetitive, transposable DNA sequences, it is plausible that these elements play an important role in generating SVs in humans. Sequencing of the diploid genome of one individual human (HuRef) affords us the opportunity to assess, for the first time, the impact of mobile elements on SVs in an individual in a thorough and unbiased fashion. In this study, we systematically evaluated more than 8000 SVs to identify mobile element-associated SVs as small as 100 bp and specific to the HuRef genome. Combining computational and experimental analyses, we identified and validated 706 mobile element insertion events (including Alu, L1, SVA elements, and nonclassical insertions), which added more than 305 kb of new DNA sequence to the HuRef genome compared with the Human Genome Project (HGP) reference sequence (hg18). We also identified 140 mobile element-associated deletions, which removed; 126 kb of sequence from the HuRef genome. Overall,; 10% of the HuRef-specific indels larger than 100 bp are caused by mobile element-associated events. More than one-third of the insertion/deletion events occurred in genic regions, and new Alu insertions occurred in exons of three human genes. Based on the number of insertions and the estimated time to the most recent common ancestor of HuRef and the HGP reference genome, we estimated the Alu, L1, and SVA retrotransposition rates to be one in 21 births, 212 births, and 916 births, respectively. This study presents the first comprehensive analysis of mobile element-related structural variants in the complete DNA sequence of an individual and demonstrates that mobile elements play an important role in generating inter-individual structural variation.