Father's Age Dictates Rate of New Mutations

With every passing year, men are increasingly likely to transmit new mutations to their children, according to the largest study yet of the so-called paternal age effect, published yesterday in Nature. The findings could help explain why older men are more likely to have a child with autism or schizophrenia than are younger men, the researchers say.On average, a 20-year-old father passes down about 25 de novomutations — which arise spontaneously in sperm cells — to his child, the study found. With each year of paternal age, the number of transmitted mutations increases by two. Mothers, in contrast, pass on about 14 de novo mutations through their eggs regardless of their age.“When we looked at the variation in the de novo mutation rate, 97 percent of it is explained by age of the father,” says lead investigator Kári Stefánsson, chief executive of deCODE Genetics, a private company in Reykjavik, Iceland. “That, in and of itself, is striking.”The new figures are the most direct estimate to date of the relationship between parental age and de novo mutations. The researchers calculated the figures based on whole-genome sequences from 78 trios of two parents and child. These families comprise a dataset that dwarfs those of previous studies, which relied on a handful of families.Several epidemiological studies in the past decade have shown that fathers older than 30 have an increased risk of having a child with autism or schizophrenia.Four papers published in April suggested that de novo mutations in protein-coding genes occur more frequently in individuals with autism than in controls. These studies also showed an effect of paternal age on the number of damaging de novo mutations but did not look at whole genomes.Read more at...SFARI, August 2012.