Zeitschriftenaufsatz
|
2018
Large-scale genetic analysis reveals mammalian mtDNA heteroplasmy dynamics and variance increase through lifetimes and generations
Autor:in
Burgstaller, J. P.; Kolbe, Thomas; Havlicek, Vitezslav; Hembach, Stephanie; Poulton, Joanna; Piálek, Jaroslav; Steinborn, Ralf; Ruelicke, Thomas; Brem, G.; Jones, Nick S.; Johnston, Iain
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Journal
Abstrakt
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.
Schlagwörter
Age Factors; Animals; DNA Copy Number Variationsgenetics; DNA, Mitochondrialgenetics; Datasets as Topic; Female; Genome, Mitochondrialgenetics; Haplotypesgenetics; Mice; Mice, Inbred C57BL; Mitochondriametabolism; Models, Animal; Oocytescytologyimmunology
Dokumententyp
Originalarbeit
CC Lizenz
CCBY
Open Access Type
Gold
ISSN/eISSN
2041-1723 -
10.1038/s41467-018-04797-2
WoS ID
PubMed ID