Yesterday the White House announced $5 billion in stimulus funding for groundbreaking medical research. One very exciting project aims to (finally) get at the many genetic causes of autism through whole-genome sequencing, and it’s happening here at Children’s. The $4.5 million project, supported by the National Institute of Mental Health, will be led by Christopher Walsh, MD, PhD, chief of Children’s Division of Genetics, with collaborators at Harvard Medical School and the Broad Institute.
About a dozen genetic aberrations have been discovered in autism, including several by researchers at Children’s (see here and here), yet there’s still no genetic explanation for about 85 percent of people with autism. Using the latest gene sequencing technology, with a heavy dose of informatics to intepret a huge flood of data, the researchers will focus first on the most valuable 2 percent of the genome that directly codes for proteins. Patients whose genetic cause remains a mystery will then have their entire genome sequenced — all 3.2 billion combinations of A, C, T and G that make up our 20,000 to 25,000 genes. It may be that critical “on/off” switches that are failing in autism lie within the vast stretches of the genome that don’t code for proteins — our so-called “junk” DNA.
The study builds on previous research in Middle Eastern populations that Walsh conducted with Michael Greenberg, PhD, now the head of Neurobiology at Harvard Medical School, and that found several genetic deletions that appear to affect these on/off switches.
These Middle Eastern families are ideal for gene-hunting: their parents share common ancestry, and linkage analyses of their extended families have already narrowed the field of candidate mutations down to just 1 percent of their genome. But within a year or two, Walsh hopes techniques will be refined enough to be applicable to many other children with autism. One big challenge will be distinguishing normal person-to-person genetic variations from variations that cause autism.