The older the parent - especially the father - the higher the incidence of new genetic mutations in the offspring, according to a paper published online this week in Nature. The paper also reports the largest resource to date of human de novo mutations (DNMs, changes to genes that present for the first time in a family, caused by a mutation in the egg or sperm of one of the parents). Understanding the mutational processes that produce sequence diversity in the human genome is of utmost importance to medical genetics and evolutionary studies.
Daniel Gudbjartsson and colleagues performed whole-genome sequence analysis of 14,688 Icelanders, including 1,548 individuals and their parents, and, for 225 of these individuals, at least one of their children, to understand how the age and sex of parents may cause alterations in DNMs. The authors identified 108,778 high-quality DNMs, with an average of 70.3 DNMs per family. They found that the number of DNMs from mothers increases by 0.37 per year of age, which is only a quarter of the 1.51 per year increase from fathers. They also found that the number of clustered mutations increases faster with the mother’s age than the father’s, and the genomic span of maternal DNM clusters is greater than that of paternal ones. In addition, the types of DNMs from mothers change substantially with age.
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