When the Autism Genome Project (AGP), an international autism genetics research consortium, published results from their analysis of a large sample of individuals with autism in June, the occasion attracted a lot of attention from popular media as well as the scientific community. The excitement was due to both the discovery of new genetic causes and biological mechanisms for autism and the promise that these discoveries hold for the development of new diagnostics and treatments.
Co-funded by Autism Speaks with other international public-private funding agencies, the AGP found several new autism risk genes by identifying copy number variants (CNVs), rare tiny insertions and deletions in the genome, which appear to disrupt more genes in individuals with autism than in the general population. Some of these CNVs are considered “highly penetrant” or sufficiently disruptive to cause autism on their own, while others only raise the risk for autism and may interact with other genetic and/or environmental risk factors to cause the disorder. Furthermore, while many CNVs are inherited, some are “de novo” meaning that they are found only in the child but not the parents.
Like other genetic risk factors reported in recent years, some of the new genes, such as SHANK2 and SYNGAP1, work at the synapse, the communication hub between neurons. Others, however, appear to cluster around specific biochemical pathways in the brain, including those involved in cell growth and motility. This novel finding suggests new biological mechanisms that could shed light on how autism develops.
Interestingly, some of the affected genes have also been implicated in intellectual disabilities, furthering the idea previously proposed by other researchers that at least some of genes are shared by different developmental disorders.
The new risk genes also support the idea that autism is caused in part by a number of “rare variants” or genetic changes found in less than one percent of the population. While each of these variants may only account for a small fraction of the cases, collectively they appear to account for a substantial percentage of individuals with ASD.
Taken together, the AGP findings point to new and exciting opportunities to develop clinical solutions for our community. Some doctors have already begun looking for the risk genes identified by the AGP and others as part of their diagnostic assessment of a child with ASD. Identification of the novel biochemical pathways involved in autism increases the chance of finding drugs that target these pathways to help recover pathway function. As part of this important effort, Autism Speaks will be co-sponsoring a research meeting in early 2011 to explore the translation of these genetic discoveries into potential therapeutics.