Robust identification of mosaic variants in congenital heart disease.
Robust identification of mosaic variants in congenital heart disease.
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DOI：
10.1007/s00439-018-1871-6
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发表时间：
2018-03
期刊：
影响因子：
5.3
通讯作者：
Gelb BD
中科院分区：
文献类型：
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作者：
Manheimer KB;Richter F;Edelmann LJ;D'Souza SL;Shi L;Shen Y;Homsy J;Boskovski MT;Tai AC;Gorham J;Yasso C;Goldmuntz E;Brueckner M;Lifton RP;Chung WK;Seidman CE;Seidman JG;Gelb BD
体细胞突变引起的嵌合体可导致多种疾病，包括癌症、发育和过度生长综合征、神经发育障碍、自体炎症性疾病和心房颤动。随着下一代测序技术的广泛使用，已经开发了多种工具来识别低频变异，特别是在癌症研究中从匹配的肿瘤-正常组织中识别低频变异。为了研究马赛克变异是否与先天性心脏病(CHD)有关，我们开发了一种管道，使用癌症体细胞变异呼叫者MuTect，从一组父母/受影响的儿童三人组(n=715)和一组健康人(n=416)的整体外显组测序(WES)数据中识别马赛克变异。这是为癌症设计的体细胞变异呼叫器在WES TRIO数据中的一种新应用。我们发现了两例嵌合型KMT2D突变，这可能是CHD的致病因素，但我们得出的结论是，总体而言，在外周血或唾液中检测到的嵌合体并不占CHD病因的很大一部分。
Mosaicism due to somatic mutations can cause multiple diseases including cancer, developmental and overgrowth syndromes, neurodevelopmental disorders, autoinflammatory diseases, and atrial fibrillation. With the increased use of next generation sequencing technology, multiple tools have been developed to identify low-frequency variants, specifically from matched tumor-normal tissues in cancer studies. To investigate whether mosaic variants are implicated in congenital heart disease (CHD), we developed a pipeline using the cancer somatic variant caller MuTect to identify mosaic variants in whole-exome sequencing (WES) data from a cohort of parent/affected child trios (n = 715) and a cohort of healthy individuals (n = 416). This is a novel application of the somatic variant caller designed for cancer to WES trio data. We identified two cases with mosaic KMT2D mutations that are likely pathogenic for CHD, but conclude that, overall, mosaicism detectable in peripheral blood or saliva does not account for a significant portion of CHD etiology.
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影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
3.7
作者：
Behjati S;Maschietto M;Williams RD;Side L;Hubank M;West R;Pearson K;Sebire N;Tarpey P;Futreal A;Brooks T;Stratton MR;Anderson J
通讯作者：
Anderson J
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
3.5
作者：
Banka, S.;Howard, E.;Donnai, D.
通讯作者：
Donnai, D.
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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