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May 1, 2012
Mutations in Three Genes Linked to Autism

Tags: Science News

Stephanie Loranger

It has long been recognized that autism runs in families, suggesting there is a genetic component to autism spectrum disorders (ASDs). Yet few genes have so far been identified, and the underlying genetics of autism—that is, how many genes contribute to the disorder and to what extent they influence a person's chances of developing the disorder—are not well understood.

Now, a consortium led by researchers from the Broad Institute in Cambridge, Massachusetts General Hospital (MGH), and six other organizations has taken a step toward addressing these questions by sequencing the genomes (the complete set of a person’s genetic information) of patients with autism and their unaffected parents.  The researchers hypothesized that de novo gene mutations account for a substantial fraction of the risk for autism. De novo is Latin for “from the beginning,” and in genetics means that the variant has spontaneously arisen and was not inherited from either parent.  Many of the 175 families whose genomes were sequenced in Boston donated DNA samples as part of the Autism Consortium study on Genotypic and Phenotypic Factors in Autism Spectrum Disorders.

The findings in the three papers referenced below revealed new genes associated with autism and were published in the April 4th issue of the journal Nature. The studies provide new insights into important genetic changes and the many biological pathways that lead to ASDs. 

Researchers identified mutations in three genes: KATNAL2, a gene whose function is unknown; SCN2A, which encodes a protein that forms a channel for sodium ions in the brain; and CHD8, which regulates gene transcription and modifies the network of proteins that surround DNA. 

These genes help explain only about one percent of the genetic risk of autism, but the findings are significant because they represent a step toward understanding the biological processes that lead to ASDs, which could help improve diagnosis and lead to new treatments.

"Autism, like many heritable disorders, results from the action of many genes—not simply a single gene as in cystic fibrosis or Huntington's disease," said senior author Mark Daly, chief of the Analytic and Translational Genetics Unit at MGH, a senior associate member of the Broad Institute and co-director of its Program in Medical and Population Genetics, and a member of the Broad Institute's Stanley Center for Psychiatric Research. "These genes hold key insights into the true biological causes of autism—insights we have been unable to gain through other lines of research."

Researchers also discovered that certain mutations associated with ASD are mainly inherited from the father. Their findings also support previous research showing an increased risk of developing ASD in children of older fathers.

Although these results only scratch the surface, they demonstrate the potential of genomic sequencing to discover more genes and the underlying biology of autism.

Journal References:

Neale, et al. (2012) Patterns and rates of exonic de novo mutations in autism spectrum disorders. doi:10.1038/nature11011
Sanders, et al. (2012) De novo mutations revealed by whole-exome sequencing are strongly associated with autism. doi:10.1038/nature10945.
O’Roak, et al. (2012) Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. doi:10.1038/nature10989.


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