Multiple genes implicated in autism

Feb 09, 2009 by Deborah Halber

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

The study, reported in the Feb. 9 advance online edition of the Proceedings of the National Academy of Sciences (PNAS), 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.

Approximately 24 percent of humans with autism have macrocephaly — head circumference above the 98th percentile — and increased brain size. Studies in ASDs patients have shown that brain size is correlated with the severity of behavioral problems.

Individuals with ASDs show deficits in social interaction, impaired communication and repetitive behaviors. According to the Centers for Disease Control, ASDs are the second most common serious developmental disability after mental retardation.

“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.

Double whammy of symptoms

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 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.

Provided by MIT

Explore further: Project pinpoints 12 new genetic causes of developmental disorders

add to favorites email to friend print save as pdf

Related Stories

Streaming release of 'Interview' test for industry

2 hours ago

Sony's "The Interview" has been a hacking target, a punchline and a political lightning rod. Now, with its release online at the same time it debuts in theaters, it has a new role: a test for a new kind of ...

Recommended for you

Obese British man in court fight for surgery

Jul 11, 2011

A British man weighing 22 stone (139 kilograms, 306 pounds) launched a court appeal Monday against a decision to refuse him state-funded obesity surgery because he is not fat enough.

2008 crisis spurred rise in suicides in Europe

Jul 08, 2011

The financial crisis that began to hit Europe in mid-2008 reversed a steady, years-long fall in suicides among people of working age, according to a letter published on Friday by The Lancet.

New food labels dished up to keep Europe healthy

Jul 06, 2011

A groundbreaking deal on compulsory new food labels Wednesday is set to give Europeans clear information on the nutritional and energy content of products, as well as country of origin.

Overweight men have poorer sperm count

Jul 04, 2011

Overweight or obese men, like their female counterparts, have a lower chance of becoming a parent, according to a comparison of sperm quality presented at a European fertility meeting Monday.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.