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

of Washington, Seattle, report on their findings online April 4, 2012 in the journal Nature.

The study by Daly and colleagues was supported by NIMH including funding under the American Recovery and Reinvestment Act. The State and Eichler studies were primarily supported by the Simons Foundation Autism Research Initiative. The studies also acknowledge the NIH's National Human Genome Research Institute, National Heart Lung and Blood Institute, and National Institute on Child Health and Human Development and other NIH components.

All three teams sequenced the protein coding parts of genes in parents and an affected child mostly in families with only one member touched by autism. One study also included comparisons with healthy siblings. Although these protein-coding areas represent only about 1.5 percent of the genome, they harbor 85 percent of disease-causing mutations. This strategy optimized the odds for detecting the few spontaneous errors in genetic transmission that confer autism risk from the "background noise" generated by the many more benign mutations.

Like larger deletions and duplications of genetic material previously implicated in autism and schizophrenia, the tiny point mutations identified in the current studies are typically not inherited in the conventional sense they are not part of parents' DNA, but become part of the child's DNA. Most people have many such glitches and suffer no ill effects from them. But evidence is building that such mutations can increase risk for autism if they occur in pathways that disrupt brain development.

State's team found that 14 percent of people with autism studied had suspect mutations five times the normal rate. Eichler and colleagues traced 39 percent of such mutations likely to confer risk to a biological pathway known to be important for communications in the brain.

Although Daly and colleagues found evidence for only a modest role of the chance mutati
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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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