Mutagenesis of human genomes by endogenous mobile elements on a population scale.
Mutagenesis of human genomes by endogenous mobile elements on a population scale.
复制标题
内源性移动元素在人群量表上对人类基因组的诱变。
DOI：
10.1101/gr.275323.121
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发表时间：
2021-12
期刊：
影响因子：
7
通讯作者：
Devine SE
中科院分区：
文献类型：
--
作者：
Chuang NT;Gardner EJ;Terry DM;Crabtree J;Mahurkar AA;Rivell GL;Hong CC;Perry JA;Devine SE
最近出现了几个大规模的Illumina全基因组测序（WGS）和全外显子组测序（WES）项目，这些项目为发现移动的元件插入（MEI）和研究这些MEI对人类基因组的影响提供了绝佳的机会。然而，这些项目也在与对数万甚至数十万个样本执行MEI发现相关的可扩展性和计算成本方面提出了重大挑战。为了应对这些挑战，我们开发了一个更有效和可扩展的移动的元素定位器工具（MELT）版本，称为CloudMELT。然后，我们使用MELT和CloudMELT在57，919个人类基因组和外显子组中进行MEI发现，发现了104，350个非冗余MEI。我们利用这些集合（1）检查驱动人类新Alu，L1和SVA MEI动员的潜在活性L1源元件;（2）检查这些MEI的群体分布和亚家族;（3）检查这些MEI对GENCODE基因，ENCODE注释特征和疾病基因的诱变。我们的研究为驱动MEI诱变的L1源元件提供了新的见解，并更好地理解了这种诱变如何影响人类基因组。
Several large-scale Illumina whole-genome sequencing (WGS) and whole-exome sequencing (WES) projects have emerged recently that have provided exceptional opportunities to discover mobile element insertions (MEIs) and study the impact of these MEIs on human genomes. However, these projects also have presented major challenges with respect to the scalability and computational costs associated with performing MEI discovery on tens or even hundreds of thousands of samples. To meet these challenges, we have developed a more efficient and scalable version of our mobile element locator tool (MELT) called CloudMELT. We then used MELT and CloudMELT to perform MEI discovery in 57,919 human genomes and exomes, leading to the discovery of 104,350 nonredundant MEIs. We leveraged this collection (1) to examine potentially active L1 source elements that drive the mobilization of new Alu, L1, and SVA MEIs in humans; (2) to examine the population distributions and subfamilies of these MEIs; and (3) to examine the mutagenesis of GENCODE genes, ENCODE-annotated features, and disease genes by these MEIs. Our study provides new insights on the L1 source elements that drive MEI mutagenesis and brings forth a better understanding of how this mutagenesis impacts human genomes.
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影响因子：
7
作者：
Gardner EJ;Lam VK;Harris DN;Chuang NT;Scott EC;Pittard WS;Mills RE;1000 Genomes Project Consortium;Devine SE
通讯作者：
Devine SE
影响因子：
4.9
作者：
Hancks DC;Kazazian HH Jr
通讯作者：
Kazazian HH Jr
DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
30.8
作者：
Dewannieux, M;Esnault, C;Heidmann, T
通讯作者：
Heidmann, T
影响因子：
3.9
作者：
Lanikova, Lucie;Kucerova, Jana;Divoky, Vladimir
通讯作者：
Divoky, Vladimir