As men age, they are more likely to pass genetic mutations on to their children. By introducing change, older men's genes appear to be a major driving force in human evolution, says Kári Stefánsson, founder of the company decode Genetics and author of a study published in August. But the mutations from a growing number of older fathers may also account for a portion of the recent increase in autism.
Because the cells that give rise to sperm divide frequently—about 23 times a year—they are much more likely to accumulate genetic copying errors than the female precursor cells, oocytes, which divide only twice before becoming eggs. The mistakes add up over a lifetime, so that the older the father, the more mutations he has in his sperm. Stefánsson and his colleagues estimate that a 70-year-old dad passes on eight times as many mutations as does a 20-year-old.
To grasp the implications, Stefánsson's team compared the whole-genome sequences of 78 Icelandic people diagnosed with autism or schizophrenia with the sequences of their fathers and mothers. Four times as many of the children's new genetic mutations came from their fathers as from their mothers. Similar results were announced in April and September by bioinformatician Evan Eichler at the University of Washington in Seattle, who demonstrated that the mutation rate in men rises linearly with age. A father 50 or older is about twice as likely as one 29 or under to have an autistic child, Eichler says.
Also in April of last year, Yale University geneticist Matthew State further quantified that risk. In families that have only one autistic child, he found, about 15 percent of the cases are linked to new mutations in sperm cells. Other studies suggest that offspring of older dads are at higher risk of schizophrenia, bipolar disorder, and epilepsy as well. Overall, advanced paternal age probably accounts for 5 percent to more than 25 percent of the risk for autism, depending on whom you ask. Because the average age of fatherhood is rising in many Western countries, more mutations are probably being passed along.
Ultimately, older fathers are a double-edged sword. Most of the mutations they pass on are harmless and some may be beneficial, even essential to our long-term survival as a species, since a genetically varied population is the raw material of evolutionary change. "Though mutations can be dangerous for the next generation," Stefánsson says, "they also increase the diversity in our genome."
