PEERING THROUGH THE MUTATIONS: Researchers have now collected enough rare mutations associated with autism to begin finding patterns of common disrupted pathways and networks. Image: iStockphoto/BanksPhotos
The underpinnings of autism are turning out to be even more varied than the disease's diverse manifestations. In four new studies and an analysis published June 8 researchers have added some major landmarks in the complex landscape of the disease, uncovering clues as to why the disease is so much more prevalent in male children and how such varied genetic mutations can lead to similar symptoms.
Large genetic studies have ruled out the idea that the malfunction of a universal gene or set of genes causes autism. And the new papers, which assessed the genomes of about 1,000 families that had only one autistic child, revealed that the genetic mutations that are likely responsible for the disorder are exceedingly rare—sometimes almost unique to an individual patient. Even some of the most common point of mutations were found in only about 1 percent of autistic children.
This finding means that the number of genes lurking behind autism spectrum disorder (ASD) is at least "in the hundreds," says Matthew State of Yale University's Program on Neurogenetics and co-author of one of the new studies. "That's a significant change from the '90s when it was [thought to be] five to 15." And getting a handle on such rare genetic mutations—even in the growing autistic population—is challenging.
Despite the rarity of these genetic code errors, researchers could detect some important patterns in the disparate data. One aberrant gene has already been linked to other social disorders. And by analyzing the role of these genes in neural development, one team of researchers suggests different genetic mutations might often disturb an entire common network.
Down the road, these developments might benefit treatment, too. "It sets the stage to think about it in a new way," says State, whose group's work appears in Neuron.
These large studies are "a good step forward," says Simon Gregory, an associate professor of molecular genetics and microbiology at Duke University, who was not involved in any of the new research. They "enable us to confirm what we'd thought about genetic rearrangements" and are "very important" in having pinpointed new relevant pathways, he notes.
Although autism has been established as a genetically based disease, it does not seem to be passed along in families in the same way that Huntington's disease is. Because those with ASD rarely end up having children of their own, mutations are unlikely to become widespread in populations.
Studies of twins and other families in which more than one child has ASD have shown that autism does have strong genetic roots, but the new studies sought to get past the commonalities and search instead families in which only one child has the disease.
"You see clearly that if you compare the autistic kids with their [unaffected] siblings, they have more of these mutations," says Dennis Vitkup of the Department of Biomedical Informatics at Columbia University and co-author of one of the new studies published in Neuron.
In assessing such a large and diverse data set several of the studies all alighted on a genetic explanation for one of the most striking patterns in ADS: why at least four times as many boys than girls are diagnosed with the disease.
Girls, it seems, might better resist the development of autistic signs: Bigger genetic disruptions are necessary to cause ASD to manifest in girls than in boys, according to the new analyses. Girls might be better protected against autism-causing genetic anomalies, Vitkup suggests, because they tend to have stronger social inclinations than boys.
Although the ability of girls to withstand genetic mayhem might seem to predispose them to become silent carriers of autism, the new analysis shows that mothers were no more likely than fathers to pass on harmful mutations.