Molecular Studies of the Paternal Age Effect

2005 senior Scholar Award in aging

It is well known that advanced maternal age increases the risk of giving birth to children with Down syndrome, and a significant effort has been made to understand the molecular basis of this increased risk. What is less well known is that advanced paternal age is also associated with an increased risk of having a child born with a new mutation that can cause one of several genetic diseases. Although the chance of older fathers having a child born with any of these conditions is much lower than the incidence of Down syndrome births in older women, the risk for older fathers can be 10-20 fold greater than that in younger men. We know very little about the cause of this ìpaternal age effect.î Our study will examine sperm from men of different ages. Using highly sensitive molecular tools, we will determine the frequency of sperm which carry new mutations that cause genetic disease. This information can tell us more about the mutation process in men and may also help explain why mutations in some genes arise only in men but not in women.