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Father's age linked to risk of autism, schizophrenia

Published August 22, 2012 3:25 pm

Genes • Older dads pass more DNA changes to children.
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New York • Children of older fathers are known to be more at risk for diseases including schizophrenia and autism. Now, a new scientific look at the genes passed down within families may have pinpointed a reason why.

The study, reported Wednesday in the journal Nature, found that older fathers transmit more new DNA variations to their children than younger dads, with each added year of age resulting in an average of 2 extra new mutations. The genetic changes occur in men as they age because of environmental factors, such as radiation, or through mistakes that occur in cell division.

The research led by scientists at Reykjavik, Iceland-based deCode Genetics Inc., is the first to quantify the number of new, or de novo, mutations that fathers hand along by age to their children. The findings may suggest that dads-to-be should consider collecting their sperm at a young age and storing it for later use, according to Alexey Kondrashov, a professor of evolutionary biology at the University of Michigan in Ann Arbor.

"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," Kondrashov wrote in an accompanying editorial that called for further study on the issue.

Mental processes may be most affected, leading to illnesses such as schizophrenia, because more genes express themselves in the human brain than elsewhere.

The de novo findings suggest it may be "reasonable to assume that the ongoing increase in 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 a higher average paternal age - and not only to better recognition of cases," Kondrashov said.

The U.S. Centers for Disease Control and Prevention in March reported that one in 88 children in the U.S. had autism or a related disorder in 2008, the latest period for which data was available. That was a 23 percent rise from 2006, the agency's researchers reported, saying it was unclear how much of the increase was due to increased awareness of the disease.

Genes are the blueprints for making all the proteins needed by the human body to grow, develop and work properly. DeCode Genetics' group looked at the DNA shared by 78 groups of Icelandic mothers, fathers, and children.

A 20-year-old father transmits on average 25 new mutations to his child while a 40-year-old transmits 65, the study found. Mothers always transmit about 15 new mutations, regardless of their age, according to the accompanying editorial.

Men probably contribute more mutations because sperm have to divide many more times than eggs, which don't actively split when women are of reproductive age, according to Kondashov.

"The only important thing when it came to explaining the mutations was the age of the father," said study author Kari Stefansson, who is also the chief executive officer of deCode Genetics. "There's very little else to be accounted for. That's a stunning observation."

Most de novo mutations are neutral, and all mutations in the genome were once de novo, Stefansson said by telephone. Once scientists determine the importance of de novo mutations relative to heredity mutations in autism, it will be easy to see how much contribution a father's age has to the child's health. That work hasn't yet been done, he said.