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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

<a href="/cs/project/GA16-23773S" target="_blank" >GA16-23773S: Fylogeografie, selekce a mutační rychlost na celogenomové úrovni: inference založená na sekvencích mtDNA myši domácí</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

—

Kód UT WoS článku

000436540700006

EID výsledku v databázi Scopus

2-s2.0-85049137379