Differences in the number of de novo mutations between individuals are due to small family-specific effects and stochasticity.
Journal
Genome research
ISSN: 1549-5469
Titre abrégé: Genome Res
Pays: United States
ID NLM: 9518021
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
18
09
2020
accepted:
14
07
2021
pubmed:
25
7
2021
medline:
11
3
2022
entrez:
24
7
2021
Statut:
ppublish
Résumé
The number of de novo mutations (DNMs) in the human germline is correlated with parental age at conception, but this explains only part of the observed variation. We investigated whether there is a family-specific contribution to the number of DNMs in offspring. The analysis of DNMs in 111 dizygotic twin pairs did not identify a substantial family-specific contribution. This result was corroborated by comparing DNMs of 1669 siblings to those of age-matched unrelated offspring following correction for parental age. In addition, by modeling DNM data from 1714 multi-offspring families, we estimated that the family-specific contribution explains ∼5.2% of the variation in DNM number. Furthermore, we found no substantial difference between the observed number of DNMs and those predicted by a stochastic Poisson process. We conclude that there is a small family-specific contribution to DNM number and that stochasticity explains a large proportion of variation in DNM counts.
Identifiants
pubmed: 34301630
pii: gr.271809.120
doi: 10.1101/gr.271809.120
pmc: PMC8415378
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1513-1518Informations de copyright
© 2021 Goldmann et al.; Published by Cold Spring Harbor Laboratory Press.
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