National Institute of Mental Health awards $4.5 million to apply next-generation technology to finding autism's causes
Children's Hospital Boston, with the Broad Institute and Harvard Medical School, has been awarded a Grand Opportunity grant from the National Institute of Mental Health as part of the federal stimulus package, to pursue "whole-genome" sequencing of patients with autism, using new technologies for rapid DNA sequencing to better understand autism's causes. The roughly $4.5 million grant, part of the federal stimulus package, officially starts September 30. All genetic sequence data will be made publicly available.
Autism frequently runs in families, and is the most highly genetic of neuropsychiatric disorders. About a dozen specific genes and mutations have been discovered, including several by researchers at Children's. Yet these genes still leave unexplained the vast majority of autism cases -- about 85 percent, says Christopher A. Walsh, MD, PhD, chief of genetics at Children's Hospital Boston, who is leading the new initiative with co-investigators Michael Greenberg, PhD, head of Neurobiology at Harvard Medical School, and a team at the Broad Institute of MIT and Harvard, led by Stacey Gabriel, PhD, and David Altshuler, MD, PhD.
The project will first focus on 85 Middle Eastern patients, previously studied in Walsh's lab, whose parents share common ancestry and who have recessive forms of autism. These patients make good initial subjects for study because linkage analyses of their extended families have already narrowed the field of candidate mutations down to just 1 percent of their genome. Because autism is extremely variable genetically, rare large families with multiple affected individuals provide a good opportunity for mapping disease-causing genes, many of which also occur in autism patients generally.
As techniques are refined, Walsh and colleagues will begin to perform and interpret genetic sequence information from other groups of autism patients, including American families. "Within a year or two, we hope to develop technology and informatics techniques that should help to understand many kids with autism," Walsh says.
The team will begin by analyzing the "exome" - the 2 percent of the genome that directly codes for proteins. For patients whose genetic cause remains a mystery, a second phase of the study will sequence and analyze the entire genome's 3.2 billion base pairs (combinations of A, C, T and G) that make up our full complement of 20,000 to 25,000 genes. In this way, the researchers hope to discover noncoding portions of the genome -- sometimes called "junk" DNA -- that don't make proteins but may contain critical switches that control gene activity.