28 July 2021

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. Christian Gilissen, theme Metabolic diseases, and colleagues investigated whether there is a family-specific contribution to the number of DNMs in offspring. This is published in the Genome Research. 

An 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 they estimated that the family specific contribution explains approximately 5.2% of the variation in DNM number. Finally, they found no substantial difference between the observed number of DNMs and those predicted by a stochastic Poisson process. 

They conclude that there is a small family-specific contribution to DNM number and that stochasticity explains a large proportion of variation in DNM counts.

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