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Spontaneous gene glitches linked to autism risk with older dads
Date:4/4/2012

Researchers have turned up a new clue to the workings of a possible environmental factor in autism spectrum disorders (ASDs): fathers were four times more likely than mothers to transmit tiny, spontaneous mutations to their children with the disorders. Moreover, the number of such transmitted genetic glitches increased with paternal age. The discovery may help to explain earlier evidence linking autism risk to older fathers.

The results are among several from a trio of new studies, supported in part by the National Institutes of Health, finding that such sequence changes in parts of genes that code for proteins play a significant role in ASDs. One of the studies determined that having such glitches boosts a child's risk of developing autism five to 20 fold.

Taken together, the three studies represent the largest effort of its kind, drawing upon samples from 549 families to maximize statistical power. They reveal sporadic mutations widely distributed across the genome, sometimes conferring risk and sometimes not. While the changes identified don't account for most cases of illness, they are providing clues to the biology of what are likely multiple syndromes along the autism spectrum.

"These results confirm that it's not necessarily the size of a genetic anomaly that confers risk, but its location specifically in biochemical pathways involved in brain development and neural connections. Ultimately, it's this kind of knowledge that will yield potential targets for new treatments," explained Thomas, R. Insel, M.D., director of the NIH's National Institute of Mental Health (NIMH), which funded one of the studies and fostered development of the Autism Sequencing Consortium, of which all three groups are members.

Multi-site research teams led by Mark Daly, Ph.D., of the Harvard/MIT Broad Institute, Cambridge, Mass., Matthew State, M.D., Ph.D., of Yale University, New Haven, Conn., and Evan Eichler, Ph.D., of the University
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
Source:Eurekalert

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