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Disease-causing genetic mutations in sperm increase with men's age

There's a lot said about a woman's ticking biological clock, but male biology doesn't age as gracefully as men might like to think.

By analyzing sperm from men of various ages, scientists from the McKusick-Nathans Institute for Genetic Medicine at Johns Hopkins have discovered that older men's sperm is more likely to contain disease-causing genetic mutations that also seem to increase a sperm's chances of fertilizing an egg.

The findings, which appear in the advance online section of the American Journal of Human Genetics, emerged during efforts to explain why a rare genetic disease is more common in children born to older fathers. The disease, Apert syndrome, leads to webbed fingers and early fusion of the skull bones, which must be surgically corrected.

The researchers found that mutation rates in sperm increased as men aged, but not enough to fully account for the increased incidence of Apert syndrome in children born to older fathers, leading to the suspicion that the disease-causing mutations confer some benefit to the sperm, despite the mutations' effects on the resulting baby.

"Mutations causing this disease occur more frequently in the sperm of older men, but the mutation rate isn't quite as high as the incidence of Apert syndrome," says Ethylin Jabs, M.D., director of the Center for Craniofacial Development and Disorders at Johns Hopkins. "For some reason, a sperm with one of these mutations is more likely to be used to make a baby than normal sperm."

While Apert syndrome itself affects only 1 in 160,000 births, the scientists believe a combination of increased mutation rate and "mutation advantage" might also be behind some of the 20 or so other genetic conditions linked to older fathers, including achrondroplasia dwarfism. These disorders begin to increase rapidly with the father's age at about the same time as maternal risks increase -- age 33 to 35. Most of the evidence for paternal age effects has come from det
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
19-Aug-2003


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