A recent study of hundreds of families with autism has discovered that spontaneous mutations can take place in a parent’s sperm or egg cells that result in an increased risk of autism, and fathers are four times more likely than mothers to pass these mutations on to their children.
Three new studies, published in the journal Nature, suggest mutations in parts of genes that code for proteins play a significant role in autism.
Scientists have been debating the relative influence of inherited risk and environmental factors in autism for decades, and few today doubt that there is a strong genetic component.
Genetic mistakes can occur across the genetic code, and many are harmless, however they can cause major issues when they occur in parts of the genome needed for brain development. Some experts say an intensified search for rare mutations could uncover enough of these to account for 15 percent to 20 percent of all autism cases and give researchers a chance to see patterns and some possible mechanisms to explain what goes wrong.
The research teams – led by Mark Daly of the Broad Institute at Harvard and Massachusetts Institute of Technology, Dr. Matthew State of Yale University and Evan Eichler of the University of Washington in Seattle – also identified several hundred new suspect genes that could eventually lead to new targets for autism treatments.
“These studies aren’t so much a breakthrough, because we knew this was coming,” said Jonathan Sebat, a professor of psychiatry and cellular and molecular medicine at the University of California, San Diego, who was not a part of the research teams. “But I’d say it’s a turning point. We now have a reliable way forward, and I think it’s fair to expect that we will find 20, 30, maybe more such mutations in the next year or two.”
They looked specifically to see where these spontaneously occurring genetic mistakes were coming from: the father’s sperm or the mother’s egg cells.
The researchers discovered that new mutations occurred four times more frequently in sperm cells than in egg cells, and the older the father, the more likely he was to have sperm with these spontaneous mutations.
Joseph Buxbaum, director of the Seaver Autism Center at Mount Sinai School of Medicine in New York and a co-author of one of the studies believes one possible reason for this is that men make sperm every day, and this high turnover rate increases the chance for errors to occur in the genetic code that could be passed on to their offspring.
“It tells us that sperm production is an imperfect process,” Buxbaum said.
“It’s primarily driven by a dad’s age. That makes sense. As you get older, there are more and more chances for problems.”
He said these findings support other studies that show older fathers have a slightly increased risk of having a child with an autism spectrum disorder.