Figure 1

The frequency or rate of mutations in the germ cells of young adults increases with age and can vary more than 2-fold between sex- and age- matched individuals. Germline mutation rates were measured as (#germline autosomal mutations)/(#diploid autosomal callable base pairs). The single data point plotted for each of the 61 Generation I males (squares) and 61 Generation I females (circles) is derived from de novo mutations discovered in a single one of their offspring. After adjusting for the effects of parental age, the mutation rate of each individual was assigned to a quartile of Age-Adjusted Mutation Rate (AAMR), with each quartile indicated by one of the four colors in the graph. Differences between Generation I individuals in their germline mutation rates are unlikely to be due to differences in the presence or absence or degree of progression of various terminal illnesses, since all Generation I subjects survived more than 20 years past the age at which they transmitted these germ cell mutations to their offspring. Furthermore, it is unlikely that any of the mutations analyzed here are strongly deleterious, since all Generation II individuals in whom the de novo mutations were identified are known to have reached maturity and had several children of their own. (Adapted from Sasani et al.⁴⁰, Fig. 2a).