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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2012-04-16T00:00:00-04:00" class="date-display-single">April 16, 2012</span></p><div class='syndicate'><h1>Spontaneous Mutations Raise Autism Risk</h1><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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</div><p>A trio of new studies has revealed several genes and biological pathways that may contribute to autism spectrum disorders (ASD). Among other insights, the findings may help explain earlier evidence linking autism risk to older fathers.</p>
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<p>ASD includes several related brain disorders, with symptoms ranging from mild to severe. People with ASD generally have trouble with social interactions and communication. Over the past few years, large research efforts have linked many rare mutations with ASD. But for at least 70% of ASD cases, there are still no known underlying genetic causes.</p>
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<p>Three separate research teams set out to examine <em>de novo</em> DNA variations, which are found in a child's DNA but not in either parent's. These spontaneous mutations arise during the creation of germ cells (egg or sperm). While less frequent than the types of genetic variations that past studies have examined, they can be very harmful. The scientists believed these variations might offer new insights into ASD risk.</p>
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<p>All 3 teams focused on exomes—the complete set of protein-coding regions in the genome. The exome represents only about 1.5% of the genome but harbors most disease-causing mutations. The researchers sequenced the exomes of affected children and their parents. One team also compared healthy siblings. In all, the scientists drew upon samples from 549 families. Two of the teams received substantial NIH funding, and all are members of the Autism Sequencing Consortium, which NIH helped to develop. The reports appeared together in the early online edition of <em>Nature</em> on April 4, 2012.</p>
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<p>The studies showed that, while a single <em>de novo</em> mutation is unlikely to fully explain disease in a given patient, sporadic mutations widely distributed across the genome can raise the risk for ASD. Many of the genes implicated in the new studies were previously tied to ASD, but some weren't. The genes tend to be related. Many are involved in fundamental developmental pathways, particularly in the brain.</p>
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<p>Notably, one of the studies found an explanation for the previous discovery that fathers of children with autism were much more likely to be older. Fathers turned out to be 4 times more likely than mothers to transmit <em>de novo</em> mutations that increase ASD risk to their children—and the number of these mutations increased with the father's age. This can be explained by the higher turnover in sperm cells. Each time DNA is copied, there's a chance that errors will become part of an offspring's DNA makeup.</p>
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<p>“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,” says Dr. Thomas R. Insel, director of NIH's National Institute of Mental Health (NIMH).</p>
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<p>“These studies begin to tell a more comprehensive story about the molecular underpinnings of autism that integrates previously disparate pieces of evidence,” says Dr. Thomas Lehner, chief of the NIMH Genomics Research Branch.</p>
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<p>There are many forms of autism under the umbrella of ASD. Given the complexities, larger studies will be needed to fully understand the genetic events that affect ASD risk.</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="http://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-pervasive-developmental-disorders/index.shtml" target="_top">Autism Spectrum Disorders</a></li><li><a href="http://www.nih.gov/researchmatters/july2008/07142008autism.htm" target="_top">Diverse Autism Mutations May Share Common Mechanism</a></li><li><a href="http://www.nih.gov/researchmatters/june2011/06132011autism.htm" target="_top">Autism Blurs Distinctions Between Brain Regions</a></li><li><a href="http://www.nimh.nih.gov/science-news/2007/tiny-spontaneous-gene-mutations-may-boost-autism-risk.shtml" target="_top">Tiny, Spontaneous Gene Mutations May Boost Autism Risk</a></li><li><a href="http://www.nih.gov/researchmatters/february2007/02262007clues.htm" target="_top">Largest-Ever Search for Autism Genes Reveals New Clues</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Patterns%20and%20rates%20of%20exonic%20de%20novo%20mutations%20in%20autism%20spectrum%20disorders" target="_blank">Nature.</a> 2012 Apr 4. doi: 10.1038/nature11011. [Epub ahead of print]<br />
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<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Sporadic%20autism%20exomes%20reveal%20a%20highly%20interconnected%20protein%20network%20of%20de%20novo%20mutations" target="_blank">Nature.</a> 2012 Apr 4. doi: 10.1038/nature10989. [Epub ahead of print] <br />
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<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=De%20novo%20mutations%20revealed%20by%20whole-exome%20sequencing%20are%20strongly%20associated%20with%20autism" target="_blank">Nature.</a> 2012 Apr 4. doi: 10.1038/nature10945. [Epub ahead of print]</p>
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<div about="/block/research-matters---popular-stori" class="ds-1col entity entity-bean bean-research-matters-block view-mode-default clearfix">
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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||
|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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