Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations
| Autor: | Burgstaller, J, Kolbe, T, Havlicek, V, Hembach, S, Poulton, J, Piálek, J, Steinborn, R, Rülicke, T, Brem, G, Jones, N, Johnston, I |
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| Přispěvatelé: | Medical Research Council (MRC), Engineering & Physical Science Research Council (EPSRC) |
| Rok vydání: | 2017 |
| Předmět: |
SELECTION
DNA Copy Number Variations TRANSMISSION Science Datasets as Topic DNA Mitochondrial DISEASE Article Mice MD Multidisciplinary RAPID SEGREGATION Animals lcsh:Science GERM-LINE Science & Technology Age Factors EVOLUTION Mitochondria Multidisciplinary Sciences MITOCHONDRIAL-DNA HETEROPLASMY Mice Inbred C57BL DRIFT EXPLAINS Haplotypes BOTTLENECK Genome Mitochondrial Models Animal Oocytes Science & Technology - Other Topics lcsh:Q Female |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) |
| ISSN: | 2041-1723 |
| Popis: | Vital mitochondrial DNA (mtDNA) populations exist in cells and may consist of heteroplasmic mixtures of mtDNA types. The evolution of these heteroplasmic populations through development, ageing, and generations is central to genetic diseases, but is poorly understood in mammals. Here we dissect these population dynamics using a dataset of unprecedented size and temporal span, comprising 1947 single-cell oocyte and 899 somatic measurements of heteroplasmy change throughout lifetimes and generations in two genetically distinct mouse models. We provide a novel and detailed quantitative characterisation of the linear increase in heteroplasmy variance throughout mammalian life courses in oocytes and pups. We find that differences in mean heteroplasmy are induced between generations, and the heteroplasmy of germline and somatic precursors diverge early in development, with a haplotype-specific direction of segregation. We develop stochastic theory predicting the implications of these dynamics for ageing and disease manifestation and discuss its application to human mtDNA dynamics. Mitochondrial populations in cells may consist of heteroplasmic mixtures of mtDNA types, and their evolution through development, aging and generations is central to genetic diseases. Here the authors dissect these population dynamics using a large mouse-based data set to characterise the dynamics of heteroplasmy mean and variance throughout life and across generations. |
| Databáze: | OpenAIRE |
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