Older Fatherhood Linked to Childhood Diseases

(Ivanhoe Newswire) -- A rare form of testicular tumor has provided scientists with new insight into how genetic changes arise in our children and could explain why certain diseases are more common in the children of older fathers.

Researchers at the University of Oxford and Copenhagen University Hospital described a surprising link between certain severe childhood genetic disorders and rare testicular tumors occurring in older men. The germ cells that make the mutant gene-carrying sperm seem to be the same cells that produce the tumor.

Although the original mutations occur only rarely in the sperm-producing cells, they encourage the mutant cells to divide and multiply. When the cell divides, it copies the mutation to each daughter cell, and the clump of mutant sperm-producing cells expands over time. Hence, the number of sperm carrying this mutation also increases as men get older, raising the risk to older fathers of having affected children.

"We think most men develop these tiny clumps of mutant cells in their testicles as they age," Professor Andrew Wilkie from the University of Oxford, who led the study, was quoted as saying. "They are rather like moles in the skin, usually harmless in themselves. But by being located in the testicle, they also make sperm -- causing children to be born with a variety of serious conditions. We call them 'selfish' because the mutations benefit the germ cell but are harmful to offspring."

The work helps to explain the origins of several serious conditions that affect childhood growth and development, as well as some conditions causing stillbirth. The research links these conditions to a single pathway controlling cell multiplication, and will be valuable to doctors explaining to parents why the disorder has arisen, and informing them that, in most cases, future children are unlikely to be affected.

The findings may also help explain one of the mysteries of genetics. Several diseases, including breast cancer, autism and schizophrenia, seem to occur more frequently in the offspring of older fathers, but the reasons are unknown. Professor Wilkie suggested that similar but milder mutations might contribute to these diseases.

"What we have seen so far may just be the tip of a large iceberg of mildly harmful mutations being introduced into our genome," he explained. "These mutations would be too weak and too rare to be picked up by our current technology, but their sheer number would have a cumulative effect, leading to disease."

SOURCE: Nature Genetics, October 25, 2009

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