Vellarikkal Shamsudheen Karuthedath, Dhiman Heena, Joshi Kandarp, Hasija Yasha, Sivasubbu Sridhar, Scaria Vinod
Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Delhi, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, Delhi, India.
Hum Mutat. 2015 Apr;36(4):419-24. doi: 10.1002/humu.22767.
The human mitochondrial genome has been reported to have a very high mutation rate as compared with the nuclear genome. A large number of mitochondrial mutations show significant phenotypic association and are involved in a broad spectrum of diseases. In recent years, there has been a remarkable progress in the understanding of mitochondrial genetics. The availability of next-generation sequencing (NGS) technologies have not only reduced sequencing cost by orders of magnitude but has also provided us good quality mitochondrial genome sequences with high coverage, thereby enabling decoding of a number of human mitochondrial diseases. In this study, we report a computational and experimental pipeline to decipher the human mitochondrial DNA variations and examine them for their clinical correlation. As a proof of principle, we also present a clinical study of a patient with Leigh disease and confirmed maternal inheritance of the causative allele. The pipeline is made available as a user-friendly online tool to annotate variants and find haplogroup, disease association, and heteroplasmic sites. The "mit-o-matic" computational pipeline represents a comprehensive cloud-based tool for clinical evaluation of mitochondrial genomic variations from NGS datasets. The tool is freely available at http://genome.igib.res.in/mitomatic/.
据报道，与核基因组相比，人类线粒体基因组具有非常高的突变率。大量线粒体突变显示出显著的表型关联，并涉及广泛的疾病。近年来，在对线粒体遗传学的理解方面取得了显著进展。新一代测序（NGS）技术的出现不仅使测序成本降低了几个数量级，还为我们提供了高质量、高覆盖率的线粒体基因组序列，从而能够解码多种人类线粒体疾病。在本研究中，我们报告了一种计算和实验流程，用于解读人类线粒体DNA变异并检查它们的临床相关性。作为原理验证，我们还展示了一项对患有Leigh病患者的临床研究，并证实了致病等位基因的母系遗传。该流程作为一个用户友好的在线工具提供，用于注释变异并查找单倍群、疾病关联和异质性位点。“mit-o-matic”计算流程代表了一个基于云的综合工具，用于从NGS数据集中对线粒体基因组变异进行临床评估。该工具可在http://genome.igib.res.in/mitomatic/免费获取。
