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Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations
JP. Burgstaller, T. Kolbe, V. Havlicek, S. Hembach, J. Poulton, J. Piálek, R. Steinborn, T. Rülicke, G. Brem, NS. Jones, IG. Johnston,
Language English Country England, Great Britain
Document type Journal Article, Research Support, Non-U.S. Gov't
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- MeSH
- Datasets as Topic MeSH
- Genome, Mitochondrial genetics MeSH
- Haplotypes genetics MeSH
- DNA, Mitochondrial genetics MeSH
- Mitochondria metabolism MeSH
- Models, Animal MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Oocytes cytology immunology MeSH
- DNA Copy Number Variations genetics MeSH
- Age Factors MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
Department for Agrobiotechnology Biotechnology in Animal Production IFA Tulln 3430 Tulln Austria
Nuffield Department of Women's and Reproductive Health University of Oxford Oxford United Kingdom
School of Biosciences University of Birmingham Birmingham B15 2TT UK
References provided by Crossref.org
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