Vanderbilt Ingram Cancer Center, Center for Quantitative Sciences, Nashville, TN 37232, USA.
Department of Applied Mathematics, Chiayi University (NCYU), Chiayi 60004, Taiwan, China.
J Genet Genomics. 2013 Dec 20;40(12):607-15. doi: 10.1016/j.jgg.2013.10.003. Epub 2013 Dec 8.
Little is known about the inheritance of very low heteroplasmy mitochondria DNA (mtDNA) variations. Even with the development of new next-generation sequencing methods, the practical lower limit of measured heteroplasmy is still about 1% due to the inherent noise level of the sequencing. In this study, we sequenced the mitochondrial genome of 44 individuals using Illumina high-throughput sequencing technology and obtained high-coverage mitochondria sequencing data. Our study population contains many mother-offspring pairs. This unique study design allows us to bypass the usual heteroplasmy limitation by analyzing the correlation of mutation levels at each position in the mtDNA sequence between maternally related pairs and non-related pairs. The study showed that very low heteroplasmy variants, down to almost 0.1%, are inherited maternally and that this inheritance begins to decrease at about 0.5%, corresponding to a bottleneck of about 200 mtDNA.
关于极低异质性线粒体 DNA（mtDNA）变异的遗传情况知之甚少。即使开发了新的下一代测序方法，由于测序的固有噪声水平，实际可测量的异质性仍约为 1%。在这项研究中，我们使用 Illumina 高通量测序技术对 44 个人的线粒体基因组进行了测序，并获得了高覆盖率的线粒体测序数据。我们的研究人群包含许多母子对。这种独特的研究设计通过分析 mtDNA 序列中每个位置的突变水平在母系相关对和非相关对之间的相关性，使我们能够规避通常的异质性限制。研究表明，非常低的异质性变体，低至接近 0.1%，是母系遗传的，这种遗传从大约 0.5%开始减少，对应于大约 200 个 mtDNA 的瓶颈。
