Structural variants are a major source of gene expression differences in humans and often affect multiple nearby genes.
Structural variants are a major source of gene expression differences in humans and often affect multiple nearby genes.
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结构变异是人类基因表达差异的主要来源，通常会影响附近的多个基因。
DOI：
10.1101/gr.275488.121
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发表时间：
2021-12
期刊：
影响因子：
7
通讯作者：
Hall IM
中科院分区：
文献类型：
--
作者：
Scott AJ;Chiang C;Hall IM
结构变异体（SV）是人类基因组多样性的重要来源，但其功能影响知之甚少。我们在GTEx项目的613个个体中绘制了61，668个SV，并测量了它们对基因表达的影响。我们估计，常见的SV是因果的eQTL的2.66%，10.5倍富集相对于它们在基因组中的丰度。重复和缺失是影响最大的变异类型，而移动的元件插入的贡献很小（eQTL的0.12%，富集1.9倍）。多组织eQTL分析表明，基因改变的SV比其他变异类型表现出更多的组成型效应，与23.08%的编码SNV和indel-eQTL相比，62.09%的编码SV-eQTL在所有组织中具有eQTL活性。非编码SV、SNV和插入缺失显示出大致相似的模式。我们还确定了539个与附近基因表达异常值相关的罕见SV。其中，62.34%是影响基因表达的非编码SV，但在调控元件处具有适度富集，表明罕见的非编码SV是基因表达差异的主要来源，但仍然难以从当前注释中预测。常见和罕见的变异体通常影响多个基因的表达：SV-eQTL平均影响1.82个邻近基因，而SNV-和indel-eQTL平均影响1.09个基因，21.34%的罕见表达改变变异体对2 - 9个不同基因有影响。我们还观察到对从SV延伸1 Mb的罕见基因表达变化的显著影响。这提供了一种机制，通过该机制，个体SV可能对表型变异具有强烈或多效性的影响。
Structural variants (SVs) are an important source of human genome diversity, but their functional effects are poorly understood. We mapped 61,668 SVs in 613 individuals from the GTEx project and measured their effects on gene expression. We estimate that common SVs are causal at 2.66% of eQTLs, a 10.5-fold enrichment relative to their abundance in the genome. Duplications and deletions were the most impactful variant types, whereas the contribution of mobile element insertions was small (0.12% of eQTLs, 1.9-fold enriched). Multitissue analysis of eQTLs revealed that gene-altering SVs show more constitutive effects than other variant types, with 62.09% of coding SV-eQTLs active in all tissues with eQTL activity compared with 23.08% of coding SNV- and indel-eQTLs. Noncoding SVs, SNVs and indels show broadly similar patterns. We also identified 539 rare SVs associated with nearby gene expression outliers. Of these, 62.34% are noncoding SVs that affect gene expression but have modest enrichment at regulatory elements, showing that rare noncoding SVs are a major source of gene expression differences but remain difficult to predict from current annotations. Both common and rare SVs often affect the expression of multiple genes: SV-eQTLs affect an average of 1.82 nearby genes, whereas SNV- and indel-eQTLs affect an average of 1.09 genes, and 21.34% of rare expression-altering SVs show effects on two to nine different genes. We also observe significant effects on rare gene expression changes extending 1 Mb from the SV. This provides a mechanism by which individual SVs may have strong or pleiotropic effects on phenotypic variation.
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影响因子：
64.8
作者：
通讯作者：
--
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：
64.8
作者：
Li X;Kim Y;Tsang EK;Davis JR;Damani FN;Chiang C;Hess GT;Zappala Z;Strober BJ;Scott AJ;Li A;Ganna A;Bassik MC;Merker JD;GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Hall IM;Battle A;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
30.8
作者：
McCarthy, Shane E.;Makarov, Vladimir;Kirov, George;Addington, Anjene M.;McClellan, Jon;Yoon, Seungtai;Perkins, Diana O.;Dickel, Diane E.;Kusenda, Mary;Krastoshevsky, Olga;Krause, Verena;Kumar, Ravinesh A.;Grozeva, Detelina;Malhotra, Dheeraj;Walsh, Tom;Zackai, Elaine H.;Kaplan, Paige;Ganesh, Jaya;Krantz, Ian D.;Spinner, Nancy B.;Roccanova, Patricia;Bhandari, Abhishek;Pavon, Kevin;Lakshmi, B.;Leotta, Anthony;Kendall, Jude;Lee, Yoon-ha;Vacic, Vladimir;Gary, Sydney;Iakoucheva, Lilia M.;Crow, Timothy J.;Christian, Susan L.;Lieberman, Jeffrey A.;Stroup, T. Scott;Lehtimaki, Terho;Puura, Kaija;Haldeman-Englert, Chad;Pearl, Justin;Goodell, Meredith;Willour, Virginia L.;DeRosse, Pamela;Steele, Jo;Kassem, Layla;Wolff, Jessica;Chitkara, Nisha;McMahon, Francis J.;Malhotra, Anil K.;Potash, James B.;Schulze, Thomas G.;Noethen, Markus M.;Cichon, Sven;Rietschel, Marcella;Leibenluft, Ellen;Kustanovich, Vlad;Lajonchere, Clara M.;Sutcliffe, James S.;Skuse, David;Gill, Michael;Gallagher, Louise;Mendell, Nancy R.;Craddock, Nick;Owen, Michael J.;O'Donovan, Michael C.;Shaikh, Tamim H.;Susser, Ezra;DeLisi, Lynn E.;Sullivan, Patrick F.;Deutsch, Curtis K.;Rapoport, Judith;Levy, Deborah L.;King, Mary-Claire;Sebat, Jonathan
通讯作者：
Sebat, Jonathan
影响因子：
4.5
作者：
Han B;Eskin E
通讯作者：
Eskin E