Father's age affects offspring

June 7, 2013 by Robert Perkins

(Medical Xpress)—In a new paper, USC Dornsife molecular and computational biologists Norman Arnheim and Peter Calabrese and their team found that the longer a man waits to have children, the greater the chance of having a child with Noonan syndrome.

Scientists in USC Dornsife have unlocked the mystery of why new cases of the genetic disease are so common—a mutation that causes the disease disproportionately increases a normal father's production of sperm carrying the disease trait.

When the mutation arises in a normal sperm stem cell, it makes that cell more likely to reproduce itself than stem cells lacking the mutation. The father then is more likely to have an affected child because more mutant stem cells result in more mutant sperm. The longer the man waits to have children, the greater the chance of having a child with Noonan syndrome, which is among the most common genetic diseases with a simple inheritance pattern.

About one of every 4,000 is a child with a new disease mutation. The disease can cause craniofacial abnormalities, , heart defects, and sometimes .

By examining the testes of 15 unaffected men, a team led by USC Dornsife molecular and Norman Arnheim and Peter Calabrese found that the new mutations were highly clustered in the testis and that the overall proportion of mutated stem cells increased with age. Their computational analysis indicated that the mutation gave a selective edge over nonmutated cells.

"There is competition between stem cells with and without the mutation in each individual testis," said Arnheim, who holds a joint at the Keck School of Medicine of USC. "But what is also unusual in this case is that the mutation which confers the advantage to testis is disadvantageous to any offspring that inherits it."

The new findings also suggested an important new molecular mechanism to explain how certain genetic disease mutations can alter sperm stem cell function leading to exceptionally high frequencies of new cases every generation.

The Arnheim and Calabrese team included postdoctoral research associates Song-Ro Yoon and Soo-Kung Choi, graduate student Jordan Eboreime, all of USC Dornsife, and Bruce Gelb of the Icahn School of Medicine at Mount Sinai in New York City. A paper detailing their research was published on June 6 in The American Journal of Human Genetics.

Explore further: Unraveling tumor growth one stem cell at a time

Related Stories

Unraveling tumor growth one stem cell at a time

June 4, 2013

Researchers at the University of Cambridge have discovered that a single mutation in a leukemia-associated gene reduces the ability of blood stem cells to make more blood stem cells, but leaves their progeny daughter cells ...

Recommended for you

Epigenetic factors linked to obesity-related disease

January 17, 2017

Obesity has been linked to "letter" changes at many different sites in the genome, yet these differences do not fully explain the variation in people's body mass index (BMI) or why some overweight people develop health complications ...

Are you ready to explore baby's genome?

January 17, 2017

When you have a baby, a nurse or a phlebotomist performs a heel stick to take a few drops of blood from your infant and sends it off to a state lab for a battery of tests. Most of the time, you never hear about the results ...

Study applies game theory to genomic privacy

January 17, 2017

It comes down to privacy—biomedical research can't proceed without human genomic data sharing, and genomic data sharing can't proceed without some reasonable level of assurance that de-identified data from patients and ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.