Children of 26537 show rates of germline de novo mutation (DNM) four- to sixfold higher than children from control parents. (A) Relationship between paternal age and number of DNMs observed in offspring. (B) Relationship between maternal age and number of DNMs observed in offspring. The observed paternal and maternal age effects seen in non-26537 offspring largely adhere to previous literature (Kong et al. 2012; Rahbari et al. 2016; Wang et al. 2020). Best fit lines and numerical values within each panel correspond to a standard linear model fit to control (nonhypermutator) data only. (C) Percentage of DNMs observed on paternally and maternally inherited chromosomes. Read-based phasing of DNMs shows an excess of maternally derived DNMs in offspring of 26537 not observed in control offspring. The alpha estimate for each set of phased mutations is shown. (Alpha) Ratio of paternal:maternal mutations.
