College Scientist Named Ellison Senior Scholar
Geneticist Norman Arnheim recognized for work on ‘paternal age effect’
By Laura Sanders
A mother’s age when she conceives can affect the health of her children. Indeed, one of every 30 children born to women over 45 will have Down syndrome.
But what about older fathers?
They, too, carry a higher risk of conceiving a child with a genetic condition, said Norman Arnheim, a USC Distinguished Professor and a leading human genetics researcher.
Arnheim is one of a few scientists investigating what he calls the “paternal age effect.”
For his work, Arnheim was recently named a Senior Scholar by the Ellison Medical Foundation, which supports aging research. Arnheim, holder of the Ester P. Dornsife Chair in Biological Sciences in USC College, will receive $977,437 over four years.
“Norm is a modest man who has very little to be modest about,” said his colleague, Myron F. Goodman, professor of biology and chemistry. “He is a world leader in human genetics, and his discoveries and achievements have carried their own weight.”
The likelihood that an older father has a child with a genetic disease is approximately 10- to 20-fold greater than that of a younger father, yet the molecular reasons behind it remain elusive, according to Arnheim. The conventional thinking has been that as men age, their cells continuously divide to produce sperm cells, increasing chances of a mistake in replicating the genome.
But Arnheim’s studies with postdoctoral scientist Irene Tiemann-Boege cast doubt on this idea.
To understand the origins of the paternal age effect, the team studied molecular changes inside sperm cells. The inherent problem with research on a very rare event, like the kind of spontaneous genetic mutations that cause achondroplasia, a form of dwarfism, is finding one such sperm in a “pool” of millions.
Arnheim, who was part of the team that developed the Polymerase Chain Reaction, which amplifies DNA to quantities that can be easily studied, turned to a technique developed by his group at USC in the late 1980s called single molecule PCR.
His group used the method to search for a DNA mutation known to cause dwarfism in sperm samples from men of different ages.
To do this, researchers add a highly sensitive “primer,” a short DNA sequence that specifically binds to the mutation, to a sample of DNA. The primer triggers the synthesis of new DNA, which alerts researchers to the presence of the specific mutation.
Examining the genetic profiles of the men’s samples, the team made a surprising find. In contradiction to expectation based on the births of individuals with achondroplasia born to men of different ages, only a small increase in the frequency of the mutation was found in sperm.
“The issue turns out to be much more complicated than anybody thought” said Arnheim. “The Ellison award will support our work to find new answers.”
Others at USC who have been named Ellison scholars are John Tower, associate professor of biological sciences, and University Professor Caleb Finch.
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