Tuesday, February 27, 2007

More on paternal age

Today's New York Times has an article, 'It Seems the Fertility Clock Ticks for Men, Too,' by Roni Rabin, that covers both declining male fertility and genetic risks tied to a father's age. The latter is something that I have written about here before, in response to a study linking autism to paternal age. That posting generated some interesting discussion and an email that pointed me to a very interesting article by Dolores Malaspina in the schizophrenia research forum: 'schizophrenia research and the male germ line.' The observations of increased risk are dramatic. I can't add much to that excellent commentary by an expert in the field, except for the small point that double-strand breaks are missing from Malaspina's list of possible genetic mechanisms. There is evidence, from Drosophila and people that double strand breaks increase with paternal age.

As discussed in comments to my earlier post, I am especially interested in knowing what genes these surprisingly specific effects act through. A 1997 PNAS article describes a few genes that are somehow quite special. In a 2003 comment in Science, Crow describes them as "hot-spots occurring almost exclusively in males and rising steeply with age. Three genes--fibroblast growth factor receptor 3 (FGFR3, mutated in achondroplasia), FGFR2 (mutated in Apert's syndrome), and RET (mutated in multiple endocrine neoplasia)--are examples of the hot-spot class. In this class, genes carry mutations that are clustered at just one or two nucleotide sites." He then discusses at length the hypothesis that these specific mutations are selected in the male germ line, a hypothesis that Goriely et al. put right in the title of their article: "Evidence for Selective Advantage of Pathogenic FGFR2 Mutations in the Male Germ Line." The title of Crow's commentary was "There's Something Curious About Paternal-Age Effects." The effects on complex behavioral diseases like autism and schizophrenia make this story even more curious.

1 comment:

Dr. Leonid Gavrilov, Ph.D. said...

Thank you for your interesting post!
I thought perhaps you may also find this related scientific study interesting to you:
Human Longevity and Parental Age at Conception