PT  - JOURNAL ARTICLE
AU  - Jakob M. Goldmann
AU  - Juliet Hampstead
AU  - Wendy S.W. Wong
AU  - Amy B. Wilfert
AU  - Tychele Turner
AU  - Marianne A. Jonker
AU  - Raphael Bernier
AU  - Martijn A. Huynen
AU  - Evan E. Eichler
AU  - Joris A. Veltman
AU  - George L. Maxwell
AU  - Christian Gilissen
TI  - Stochasticity explains differences in the number of <em>de novo</em> mutations between families
AID  - 10.1101/2020.09.18.303727
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.18.303727
4099  - http://biorxiv.org/content/early/2020/09/20/2020.09.18.303727.short
4100  - http://biorxiv.org/content/early/2020/09/20/2020.09.18.303727.full
AB  - 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 significant family-specific contribution. This result was corroborated by comparing DNMs of 1669 siblings to those of age-matched unrelated offspring. In addition, by modeling DNM data from 1714 multi-offspring families we estimated that the family specific contribution explains approximately 5.2% of the variation in DNM number. Furthermore, we found no significant difference between the observed number of DNMs and those based on a stochastic Poisson process. We conclude that a family-specific contribution to DNMs is small and that stochasticity explains a large proportion of variation in DNM counts.