Mitochondrial and nuclear disease panel (Mito-aND-Panel): Combined sequencing of mitochondrial and nuclear DNA by a cost-effective and sensitive NGS-based method.
Mitochondrial and nuclear disease panel (Mito-aND-Panel): Combined sequencing of mitochondrial and nuclear DNA by a cost-effective and sensitive NGS-based method.
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DOI：
10.1002/mgg3.500
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发表时间：
2018-11
影响因子：
2
通讯作者：
Diebold I
中科院分区：
文献类型：
--
作者：
Abicht A;Scharf F;Kleinle S;Schön U;Holinski-Feder E;Horvath R;Benet-Pagès A;Diebold I
线粒体疾病的诊断是具有挑战性的，因为这些条件的临床变异性和遗传异质性。下一代测序（NGS）技术为核和线粒体DNA（mtDNA）分析提供了一个强大的高通量平台。我们开发了一种定制的Agilent SureSelect线粒体和核疾病面板（Mito‐aND‐Panel）捕获试剂盒，该试剂盒允许并行富集，用于随后基于NGS的核线粒体疾病相关基因和完整mtDNA基因组的序列分析。将富集的mtDNA与核基因同时测序与线粒体基因组的分离测序和全外显子组测序（WES）进行比较。与使用桑格测序/SNaPshot和WES的标准诊断程序相比，Mito‐aND‐Panel可以准确检测低水平mtDNA异质性，因为其测序深度非常高，这对于识别母系遗传性线粒体疾病至关重要。我们建立了一种基于NGS的方法，结合完整mtDNA和核基因的测序，与传统方法相比，该方法能够更灵敏地检测mtDNA突变的异质性。由于该方法促进了大队列中mtDNA变异的分析，具有成本效益且易于设置，因此我们预计这是临床诊断应用中基于序列的遗传诊断的高度相关方法。
The diagnosis of mitochondrial disorders is challenging because of the clinical variability and genetic heterogeneity of these conditions. Next‐Generation Sequencing (NGS) technology offers a robust high‐throughput platform for nuclear and mitochondrial DNA (mtDNA) analyses. We developed a custom Agilent SureSelect Mitochondrial and Nuclear Disease Panel (Mito‐aND‐Panel) capture kit that allows parallel enrichment for subsequent NGS‐based sequence analysis of nuclear mitochondrial disease‐related genes and the complete mtDNA genome. Sequencing of enriched mtDNA simultaneously with nuclear genes was compared with the separated sequencing of the mitochondrial genome and whole exome sequencing (WES). The Mito‐aND‐Panel permits accurate detection of low‐level mtDNA heteroplasmy due to a very high sequencing depth compared to standard diagnostic procedures using Sanger sequencing/SNaPshot and WES which is crucial to identify maternally inherited mitochondrial disorders. We established a NGS‐based method with combined sequencing of the complete mtDNA and nuclear genes which enables a more sensitive heteroplasmy detection of mtDNA mutations compared to traditional methods. Because the method promotes the analysis of mtDNA variants in large cohorts, it is cost‐effective and simple to setup, we anticipate this is a highly relevant method for sequence‐based genetic diagnosis in clinical diagnostic applications.
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影响因子：
3.7
作者：
Gould MP;Bosworth CM;McMahon S;Grandhi S;Grimberg BT;LaFramboise T
通讯作者：
LaFramboise T
DOI：
10.1016/j.jmoldx.2017.01.011
发表时间：
2017-05
期刊：
The Journal of molecular diagnostics : JMD
影响因子：
--
作者：
Jennings LJ;Arcila ME;Corless C;Kamel-Reid S;Lubin IM;Pfeifer J;Temple-Smolkin RL;Voelkerding KV;Nikiforova MN
通讯作者：
Nikiforova MN
影响因子：
3.9
作者：
Bannwarth, S;Procaccio, V;Paquis-Flucklinger, V
通讯作者：
Paquis-Flucklinger, V
影响因子：
3.8
作者：
Falk MJ;Shen L;Gonzalez M;Leipzig J;Lott MT;Stassen AP;Diroma MA;Navarro-Gomez D;Yeske P;Bai R;Boles RG;Brilhante V;Ralph D;DaRe JT;Shelton R;Terry SF;Zhang Z;Copeland WC;van Oven M;Prokisch H;Wallace DC;Attimonelli M;Krotoski D;Zuchner S;Gai X;MSeqDR Consortium Participants;MSeqDR Consortium participants: Sherri Bale, Jirair Bedoyan, Doron Behar, Penelope Bonnen, Lisa Brooks, Claudia Calabrese, Sarah Calvo, Patrick Chinnery, John Christodoulou, Deanna Church,;Rosanna Clima, Bruce H. Cohen, Richard G. Cotton, IFM de Coo, Olga Derbenevoa, Johan T. den Dunnen, David Dimmock, Gregory Enns, Giuseppe Gasparre,;Amy Goldstein, Iris Gonzalez, Katrina Gwinn, Sihoun Hahn, Richard H. Haas, Hakon Hakonarson, Michio Hirano, Douglas Kerr, Dong Li, Maria Lvova, Finley Macrae, Donna Maglott, Elizabeth McCormick, Grant Mitchell, Vamsi K. Mootha, Yasushi Okazaki,;Aurora Pujol, Melissa Parisi, Juan Carlos Perin, Eric A. Pierce, Vincent Procaccio, Shamima Rahman, Honey Reddi, Heidi Rehm, Erin Riggs, Richard Rodenburg, Yaffa Rubinstein, Russell Saneto, Mariangela Santorsola, Curt Scharfe,;Claire Sheldon, Eric A. Shoubridge, Domenico Simone, Bert Smeets, Jan A. Smeitink, Christine Stanley, Anu Suomalainen, Mark Tarnopolsky, Isabelle Thiffault, David R. Thorburn, Johan Van Hove, Lynne Wolfe, and Lee-Jun Wong
通讯作者：
Claire Sheldon, Eric A. Shoubridge, Domenico Simone, Bert Smeets, Jan A. Smeitink, Christine Stanley, Anu Suomalainen, Mark Tarnopolsky, Isabelle Thiffault, David R. Thorburn, Johan Van Hove, Lynne Wolfe, and Lee-Jun Wong
影响因子：
4.4
作者：
Dinwiddie DL;Smith LD;Miller NA;Atherton AM;Farrow EG;Strenk ME;Soden SE;Saunders CJ;Kingsmore SF
通讯作者：
Kingsmore SF