Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081766%3A_____%2F18%3A00491104" target="_blank" >RIV/68081766:_____/18:00491104 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1038/s41467-018-04797-2" target="_blank" >http://dx.doi.org/10.1038/s41467-018-04797-2</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-018-04797-2" target="_blank" >10.1038/s41467-018-04797-2</a>

Result language
angličtina
Original language name
Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10603 - Genetics and heredity (medical genetics to be 3)

Project
<a href="/en/project/GA16-23773S" target="_blank" >GA16-23773S: Phylogeography, selection and mutation rate at the whole-genome level: Inference from mtDNA sequences of the house mouse</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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