Very Low-Level Heteroplasmy mtDNA Variations Are Inherited in Humans |
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| Authors: | Yan Guo Chung-I Li Quanhu Sheng Jeanette F Winther Qiuyin Cai John D Boic Yu Shyr |
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| Institution: | 1. Vanderbilt Ingram Cancer Center, Center for Quantitative Sciences, Nashville, TN 37232, USA;2. Department of Applied Mathematics, Chiayi University (NCYU), Chiayi 60004, Taiwan, China;3. Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen DK-2100, Denmark;4. Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA;5. National Council on Radiation Protection & Measurements, Bethesda, MD 20814, USA;1. Wellcome Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK;1. Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, United Kingdom;2. University of Manchester, Manchester M13 9PT, United Kingdom;1. Center for Mitochondrial and Epigenomic Medicine, the Children’s Hospital of Philadelphia and the Department of Pathology and Laboratory Medicine, University of Pennsylvania, Colket Translational Research Building, Philadelphia, PA 19104-4302, USA;2. Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, Irvine, CA 92697, USA;3. Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA;4. Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, CA 92697, USA;5. Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA;1. Miller School of Medicine, University of Miami, Miami, FL, USA |
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| Abstract: | 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. |
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| Keywords: | Maternal inheritance Next-generation sequencing High-depth sequencing Heteroplasmy mtDNA mutations Bottleneck |
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