Fig. 2
From: New insights into the generation and role of de novo mutations in health and disease
Timing of de novo mutations (DNMs). Sperm cells have undergone approximately 100 to 150 mitoses in a 20-year-old man, whereas oocytes have gone through 22 mitoses in a woman of the same age (left). As a result of errors in both replication of the genome and repair of DNA damage occurring during parental embryogenesis, gametogenesis, or as postzygotic events in the offspring, DNMs arise in each new generation. Advanced parental age is associated with an increase in the number of de novo mutations (right). The male germline adds 23 mitoses per year, entailing that a spermatogonial stem cell in a 40-year-old man has undergone more than 600 cell mitoses. Each additional year in paternal age at conception adds one to three de novo mutations to the genome of the offspring. Oogenesis has a fixed number of mitoses, but mutations accumulate over time possibly owing to failure to repair DNA damage. The increase in number of de novo mutations with maternal age is lower: 0.24 extra de novo mutations for each additional year of maternal age at conception. Cell lineages modified from [238]. Somatic cells are showed in orange, the male germline is shown in blue, and the female germline is shown in purple. Blue stars represent postzygotic mutations present in the germline and in somatic cells; yellow stars represent mutations arising exclusively in the germline; red stars represent somatic mutations arising during embryonic development or post-natal life which are absent from germline cells. Figure footnotes: 1The ratio of paternal to maternal mutations originating from parental gonosomal mosaicism is 1:1; 2the ratio of paternal to maternal germline de novo mutations is 4:1; 3the ratio of paternal to maternal postzygotic de novo mutations is 1:1; 4this range is based on the average number of de novo mutations published elsewhere [9, 10, 12, 13, 15] irrespective of parental age