Veterinärmedizinische Universität Wien Forschungsinformationssystem VetDoc

Gewählte Publikation:

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Publikationstyp: Zeitschriftenaufsatz
Dokumentart: Originalarbeit

Publikationsjahr: 2018

AutorInnen: Burgstaller, JP; Kolbe, T; Havlicek, V; Hembach, S; Poulton, J; Piálek, J; Steinborn, R; Rülicke, T; Brem, G; Jones, NS; Johnston, IG

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

Quelle: Nat Commun. 2018; 9(1):2488


Entstanden unter Nutzung der Ressourcen von
VetCore (Genomics);

Autor/innen der Vetmeduni Vienna:

Brem Gottfried
Burgstaller Jörg
Havlicek Vitezslav
Kolbe Thomas
Rülicke Thomas
Steinborn Ralf

Beteiligte Vetmed-Organisationseinheiten
Institut für Tierzucht und Genetik, Abteilung für Reproduktionsbiologie
Institut für Labortierkunde
VetCore


Abstract:
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.


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