New Study: Autism has Multiple Genetic Roots
Jun 9, 2010 Robert Adler
A major new study applying state-of-the-art genetic screening has found that many different genetic changes can contribute to the risk that a child will develop autism.
The study’s authors say that although it’s possible that each child with autism or an autism spectrum disorder (ASD) has a unique pattern of genetic changes underlying the disorder, the changes the researchers have identified impact shared biological pathways.
That means that medications can be developed with the aim of improving the functioning of those pathways and, eventually, improving the outcomes for many autistic children.
Autism and Autism Spectrum Disorder Signs and Symptoms
Autism is a major disorder of development that affects a child’s attachment, communication, cognitive and emotional development, and behavior.
The diagnostic category of Autism Spectrum Disorder, or ASD, reflects the realization by researchers and clinicians that each symptom of the disorder can range from mild to severe, and that individuals with ASD can experience very different patterns and outcomes.
Experts agree that autism and ASD are increasing in frequency. Autism Speaks, the largest autism research and advocacy society in the U.S., estimates that one out of every 110 children, and one out of every 70 boys will develop autism or ASD.
Genetic Screening for ASD-related Variants
Based on previous autism research, the researchers used state-of-the-art high resolution genetic screening to look for copy number variants (CNVs) in nearly 1000 children diagnosed with ASD and more than 1000 controls. CNVs are short stretches of DNA that are repeated a different number of times in different people. They are important because they can influence how a particular gene functions.
The study’s major finding was that children with ASD have significantly more CNVs affecting their genes than children without ASD. Children with ASD have 20 percent more CNVs in general, and 70 percent more CNVs impacting genes known to be associated with ASD or cognitive problems. Significantly, many of the genes that are affected control important functions such as cell proliferation and cell-to-cell communication.
Some of the newly discovered genetic variants are inherited, and are found in parents or siblings of children with them. Others, however, seem to have originated spontaneously in the affected child, and do not appear in other family members.
While these findings add significantly to the scientific understanding of the genetic and biological underpinnings of ASD, the immediate usefulness is limited. That’s because there are a very large number of CNVs, and each child shows a different pattern of genetic changes. Each of these changes is rare; no CNV showed up in more than one percent of the children studied.
“This will lead to a paradigm shift in understanding the etiology of autism,” says Stephen Scherer, a senior scientist at The Hospital for Sick Children in Toronto, Canada. “Until now, most scientists thought individuals with autism shared common genes. We now think each person has his own rare variations.”
Implications for Parents and Children with Autism and Autism Spectrum Disorder
The researchers are encouraged, however, because many of the CNVs they found do impact shared biological pathways, leading, for example to altered cell proliferation, adhesion, motility or signaling, all of which can affect the development of the central nervous system.
Scherer sees this convergence of effects as a key to treatment. “Another very important finding is that we can tie these genes together into similar biological pathways. That will let us design targeted treatments.”
The researchers say that the first tangible help for families from this research will be in the areas of early screening for ASD and genetic counseling.
These very detailed genetic studies, called microarray or gene chip screenings, are already available in the province of Ontario, Canada. As they become more widely available, and, hopefully, covered by insurance, pediatricians or parents who are concerned about a child’s development will be able to have the child screened for hundreds of possible CNVs.
If significant CNVs show up, behavioral treatment can be started early. That has been shown to improve children’s outcomes significantly. “If we provide stimulation early, while the brain is still plastic, we can improve cognitive development, social interaction and communication,” says Geri Dawson, Chief Science Officer of Autism Speaks, the major sponsor of the research project.
In addition, a detailed knowledge of a child’s CNVs can help genetic counselors give parents a more accurate understanding of the degree to which other siblings should be monitored, and the risk of conceiving another child with ASD.
The Emerging Picture of Autism and ASD
What this new research suggests is that autism and ASD probably result from the interaction between many different genes and a child’s environment. Rather than search for one single cause and one “magic bullet,” researchers will try to find as many significant genetic variants as possible, link them to the biological functions and pathways they control, and then search for medications that can improve or normalize the functioning of damaged pathways.
The researchers are quick to point out that much more work is needed, some of which is already happening, to turn these early findings into generally available tests and treatments. They are cautious, but hopeful. “Our investments are finally starting to pay off,” says Dawson. “What’s needed now is to translate these findings into better behavioral and medical interventions as soon as possible.”
Tony Monaco, at Oxford University in the UK, is doing just that. "We have another 1500 families that we're studying to try to finish this picture," he says. "Our goal is to do pilot studies to move this into practice."
Source:
Dalili Pinto et al., "Functional impact of global rare copy number variation in autism spectrum disorders," Nature, 9 June 2010 (DOI: 10.1038/nature09146)
