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Multiple Genes Implicated in Autism

By Drug Discovery Trends Editor | February 10, 2009

By pinpointing two genes that cause autism-like symptoms in mice, researchers at MIT’s Picower Institute for Learning and Memory have shown that multiple, interacting genetic risk factors may influence the severity of autistic symptoms.

The study lends support to researchers’ long-suspected belief that in individuals whose autism is genetic in origin, more than one gene is implicated.

The work could lead to drugs targeting signaling mechanisms between the two interacting genes responsible for some autism spectrum disorders (ASDs) symptoms. The molecular intersection of the two genes’ pathways in the brain may also serve as a diagnostic target or biomarker for a subset of individuals with ASDs.

‘We found that two genetic risk factors for ASDs act cooperatively in mice to influence brain size and social behavior, both of which are altered in ASDs,’ said Damon T. Page, a Picower Institute postdoctoral fellow and lead investigator of the study.

‘Our results provide evidence that the severity of autistic symptoms may be the product of variations in DNA in multiple locations in the genome,’ Page added.

‘An important implication is that because the majority of instances of autism appear to involve multiple genes, specific gene combinations may worsen effects. New therapeutics may one day be developed that influence particular signaling mechanisms in the disorder,’ said Mriganka Sur, the Newton Professor of Neuroscience and head of the MIT Department of Brain and Cognitive Sciences.

Page and colleagues found that mice carrying mutations in two different candidate autism susceptibility genes have more severe symptoms than those with only a single mutation.

The researchers studied the effects on mouse brain development and behavior of mutations in the PTEN gene, which encodes the phosphatase and tensin homolog protein, and the serotonin transporter gene.

The researchers found that mice with a mutation in PTEN alone, or in the serotonin transporter gene alone, had brains that were larger than normal, while mice with simultaneous mutations in PTEN and serotonin transporter genes had even larger brains.

In female mice, a mutation in PTEN impaired sociability, while those that also had a mutation in serotonin transporter had worse symptoms. The authors concluded that interaction between the two genes influences brain growth and sociability.

The authors concluded that interaction between the two genes influences brain growth and sociability in mice, noting that mutations in Serotonin transporter may be one of multiple risk factors that could modify the severity of autistic symptoms in individuals who previously developed mutations in PTEN. Future work will be aimed at characterizing how genetic, environmental, and pharmacological manipulations impact these animals’ autism-related traits.

Release Date: February 9, 2009
Source: Massachusetts Institute of Technology


Filed Under: Genomics/Proteomics

 

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