The Simons Simplex Collection's (SSC) primary goal was to create a permanent repository of genetic material from 2,700 families, each of which has one child affected with an autism disorder and unaffected parents and siblings. Because the disorder is present in just one child and not the whole family, the markers and defects causing the disorder, at least in these families, are not inherited, meaning they arise from environmental factors or spontaneously.
The ultimate goal is homing in on the varied genetic factors that contribute to autism spectrum disorders.
Now the value of this data bank is becoming very clear. Sweeping the protein-coding regions in nearly all the 2,700 families whose genomes are banked in the SCC, researchers have nailed down more than two dozen high-confidence risk genes for autism.
That might not sound impressive, but trust us, it’s big news.
For years, the roots of autism have been a puzzle wrapped up in an enigma shrouded in mystery. Does it begin in the womb? Is it early stage or late stage? Do vaccinations cause it? (No!) And what about the incredible disparity between boys, who are likely to have what’s called higher-IQ autism, and girls, who have less autism overall but a greater prevalence of lower-IQ autism?
All these questions and more are being answered, slowly, not unlike opening a barnacle-encrusted treasure chest, by the researchers at SSC bankrolled by the seemingly bottomless pockets of the hedge fund wizard James Simons. “For more than a decade, the field has been searching for a systematic way to identify autism risk genes,” says Matthew State, the SSC’s PI. “This makes the definitive point that there’s a way forward in gene discovery in autism.”
Indeed. Within the SSC data bank, seven particular genes were found to be mutated in three or more separate autism cases: That’s pretty much a smoking gun. Barely a question, now, that those seven particular genes are vulnerable to the kinds of mutations that bring on autism. And what’s more, researchers discovered another twenty genes that are mutated in two autism cases. For these genes, it’s 90 percent certain they’re part of the autism picture.
“We have a set of genes for which now, if people see a likely gene-disrupting mutation when sequencing a young child, there’s a high risk of the child developing autism, and that, to my mind, is pretty powerful stuff,” says Evan Eichler of the University of Washington, a Simons Foundation Autism Research Initiative (SFARI) Investigator who leads one of the laboratories that contributed to the study. “Recognizing this early on may allow for earlier interventions, such as behavioral therapies, improving outcomes in children.”
Beyond the undoubtable importance of the SSC’s findings, their cooperative model is also noteworthy. Three labs: Eichler’s, in Washington; State’s, at UC San Francisco; and Michael Wigler’s at Cold Spring Harbor Lab in New York worked together to make this analysis possible. Thanks to the SSC, there’s a spirit of cooperation among these researchers who might otherwise be competitors. They’ve published their findings in a joint paper in Nature, titled "The contribution of de novo coding mutations to autism spectrum disorder."
Though this discovery is definitely a big deal, we’re sure it’s small compared to the revelations the SSC may reveal to researchers in the future. They only looked at spontaneous, or “de novo” mutations, and they only looked at the protein-coding part of the genome, called the exome. That’s just 1.5 percent of the genome. But, says Eichler, “If we can explain 27 percent of simplex autism from this small sliver of a sliver of DNA, there’s a lot more to be mined from complete genome sequencing of the SSC,” Eichler says. “Stay tuned.”