Autism breakthrough: Harvard, Yale researchers identify new genes linked to disorder

In three separate studies, scientists have identified mutations in three new genes believed to be linked with autism, using a method they hope will be able to isolate hundreds of genes related to the disorder within the next three years.  The researchers expect that finding these genes will lead the way to a cure.

The gene mutations—CHD8, SNC2A and KATNAL2—are all ‘de-novo’, meaning they show up in the genes of affected children for the first time and result from mutations in the production of sperm or egg.

Combined, the studies from Yale University, University of Washington, and Harvard University, in collaboration with researchers from Mount Sinai School of Medicine in New York City, involved 580 families of children with autism.  The mutations were discovered through a state-of-the-art technology known as exome sequencing, which analyzes all the protein coding regions of the human genome.  This accounts for approximately 23,000 genes, though only 2 percent of the entire genome.

However, the researchers who conducted the study believe that 2 percent of the genome may be able to identify 200 hundred mutations involved in autism spectrum disorders within as little as three years, adding to the 100 genes that have already been identified.

“We can say with a lot of authority, based on empirical data, if we can sequence 5,000 independent cases of autism, we will be able to identify several hundred mutations linked to autism,” said Dr. Joseph Buxbaum, director of the Seaver Autism Center and professor of psychiatry, genetics and genomic sciences, and neuroscience at Mount Sinai School of Medicine in New York City and collaborating author in the Harvard study.

“If we can put the resources behind it, we’ll likely be able to identify 50 percent of autism-related gene mutations in the next three years.  That’s pretty incredible,” Buxbaum said.

In an interview with Fox CT, Dr. Stephan Sanders, a postdoctoral fellow at Yale University and the first author of the Yale study, estimated their lab alone will be able to find 25 more genes linked to autism by the end of 2012.

“If we can find enough genes and then link them together, then we can understand what the cause of autism is,” Sanders told Fox CT. “Finding those genes is like filling in the puzzle of a jigsaw.”

Prior research has indicated that many gene mutations, and subsequent gene interactions based on those mutations, are involved in development of autism.  Buxbaum estimated approximately 800-1000 mutations may be linked to the disorder.

However, he added, in order to begin to develop treatments targeting the social, language and other developmental difficulties that characterize the disorder, only half of those genes need to be identified.

“It’s hard in biology to get to 100 percent, but when you get to 50 percent, you can start doing systems biology, which is looking at the groups of genes that are important in the disorder,” Buxbaum said. “We think now in systems medicine, if you find a group that works together, there are driver genes within the group which define how all the other genes are regulated.  So maybe that one driver gene is the one you want to develop a drug for.”

“This is a short term plan,” he added. “This is not a 20-year plan, this is a three-year plan to define 200 more autism genes…We feel strongly we have a roadmap.”

Sanders agreed, adding: “For the first time we have a route forward, an understanding of how to do autism research to find the true biological cause of autism.”

Autism Speaks vice president for scientific affairs Dr. Andy Shih, who reviewed the study, said the results are the next steps in understanding genetic risk factors.  “What these papers represent is another step taken based on progress and advances in technology,” Shih said.

“Technology, especially exome sequencing, has progressed very rapidly—like Morse law in computers advanced their capacity,” he continued.  “This is an even more accelerated course.”

According to Shih, while the studies were limited in that they only studied 2 percent of the genome, they were still a “significant” step forward in terms of understanding genetic risk factors.

“We know autism is caused by the interplay of genetic and environmental risk factors, and so we’re starting to zero in on certain genetic elements, just like cancer,” Shih said. “So we are now seeing some of that complex interplay.”

The studies were published in the journal Nature.

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