Accurate mapping of mitochondrial DNA deletions and duplications using deep sequencing.
Accurate mapping of mitochondrial DNA deletions and duplications using deep sequencing.
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DOI：
10.1371/journal.pgen.1009242
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发表时间：
2020-12
期刊：
影响因子：
4.5
通讯作者：
Larsson E
中科院分区：
文献类型：
--
作者：
Basu S;Xie X;Uhler JP;Hedberg-Oldfors C;Milenkovic D;Baris OR;Kimoloi S;Matic S;Stewart JB;Larsson NG;Wiesner RJ;Oldfors A;Gustafsson CM;Falkenberg M;Larsson E
线粒体DNA（mtDNA）中的缺失和重复会导致线粒体疾病，并在癌症和年龄相关疾病等疾病中积累，但缺乏可以容易检测和区分这两种类型事件的经验证的高通量方法。在这里，我们建立了一个计算方法，MitoSAlt，准确识别，定量和可视化的mtDNA缺失和重复的基因组测序数据。我们的方法在模拟测序读数和具有单缺失和重复的人类患者样品上进行了测试，以验证其准确性。应用于小鼠模型的mtDNA维持性疾病证明了即使在低水平的异质性检测缺失和重复的能力。线粒体基因组中的缺失导致各种罕见疾病，但也与更常见的疾病有关，如神经退行性疾病，2型糖尿病和正常的衰老过程。人们也越来越意识到，与人类疾病相关的mtDNA重复可能比以前认为的更常见。尽管它们的临床重要性，我们目前的知识的丰度，特征和多样性的mtDNA缺失和重复是支离破碎的，并在很大程度上基于传统的低通量分析提供的有限的观点。在这里，我们描述了一种生物信息学方法，MitoSAlt，可以准确地映射和分类mtDNA缺失和重复使用高通量测序。将这种方法应用于线粒体缺陷的小鼠模型，发现了大量的重复，这表明这些重复以前可能被低估了。
Deletions and duplications in mitochondrial DNA (mtDNA) cause mitochondrial disease and accumulate in conditions such as cancer and age-related disorders, but validated high-throughput methodology that can readily detect and discriminate between these two types of events is lacking. Here we establish a computational method, MitoSAlt, for accurate identification, quantification and visualization of mtDNA deletions and duplications from genomic sequencing data. Our method was tested on simulated sequencing reads and human patient samples with single deletions and duplications to verify its accuracy. Application to mouse models of mtDNA maintenance disease demonstrated the ability to detect deletions and duplications even at low levels of heteroplasmy. Deletions in the mitochondrial genome cause a wide variety of rare disorders, but are also linked to more common conditions such as neurodegeneration, diabetes type 2, and the normal ageing process. There is also a growing awareness that mtDNA duplications, which are also relevant for human disease, may be more common than previously thought. Despite their clinical importance, our current knowledge about the abundance, characteristics and diversity of mtDNA deletions and duplications is fragmented, and based to large extent on a limited view provided by traditional low-throughput analyses. Here, we describe a bioinformatics method, MitoSAlt, that can accurately map and classify mtDNA deletions and duplications using high-throughput sequencing. Application of this methodology to mouse models of mitochondrial deficiencies revealed a large number of duplications, suggesting that these may previously have been underestimated.
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影响因子：
3.5
作者：
Nicholls TJ;Zsurka G;Peeva V;Schöler S;Szczesny RJ;Cysewski D;Reyes A;Kornblum C;Sciacco M;Moggio M;Dziembowski A;Kunz WS;Minczuk M
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Minczuk M
影响因子：
14.9
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7
作者：
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通讯作者：
Frith, Martin C.
DOI：
10.1016/0006-291x(90)90497-b
发表时间：
1990-08-16
影响因子：
3.1
作者：
IKEBE, S;TANAKA, M;OZAWA, T
通讯作者：
OZAWA, T
影响因子：
158.5
作者：
MORAES, CT;DIMAURO, S;ROWLAND, LP
通讯作者：
ROWLAND, LP