Older fathers pass on more genetic mutations to their offspring than younger fathers, which may put their children at higher risk of autism, schizophrenia, and other diseases, according to a new study in Nature.
Lead author Kari Stefansson, CEO of deCODE Genetics in Iceland, and his team sequenced the genomes of 78 families—comprising 219 individuals—which included 44 children with autism and 21 with schizophrenia. For comparison, they also sequenced the genome of 1,859 other Icelanders.
Previous research found that risk of autism is higher among older fathers, but this study is the first to attempt to quantify that risk.
Researchers found that, on average, a 20-year-old father's genetic material had 25 de novo—or new—mutations and a 40-year-old father had 65, which means that the number of de novo mutations in the father's sperm cells increased by two every year.
On the other hand, the mother typically transmits 14 de novo mutations to a child regardless of her age. The study found no correlation between the mother's age and autism rates.
This discrepancy is the result of the fact that sperm cells divide rapidly—once every 15 days—whereas egg cells are much more stable. Rapid division inevitably leads to DNA replication errors, causing these de novo mutations.
Most of these mutations are harmless, but occasionally they can be significant. Researchers note that the brain in particular is most susceptible to mutations, likely because it expresses more genes than any other organ.
De novo mutations not the only risk factor for autism
Alexey Kondrashov, professor of evolutionary biology at the University of Michigan, wrote in an accompanying editorial that "the incidence and prevalence of autism in many human populations could be due, at least in part, to the accumulation of mutations resulting from relaxed selection and higher average paternal age."
According to government statistics, the birthrate of fathers 40 years of age or older has increased more than 30% since 1980, although the diagnosis rate for autism increased tenfold, the New York Times reports. This mismatch suggests that there are likely other factors that contribute to the overall increase in autism diagnoses.
Whether or not de novo mutations contributed to a rise in other mental disorders, such as schizophrenia, is still unclear. However, Kondrashov says that "if the paternal-age effect on the de novo mutation rate does lead to substantially impaired health in the children of older fathers, then collecting the sperm of young adult men and cold-storing it for later use could be a wise individual decision" (Lopatto, Bloomberg News/Washington Post, 8/22; Naik, Wall Street Journal, 8/22; Storrs, HealthDay, 8/22; Carey, New York Times, 8/22).
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