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From Genetic Discoveries to Improved Diagnosis & Treatment

Guest post by geneticist Ryan Yuen, PhD. Dr. Yuen is the recipient of an Autism Speaks postdoctoral fellowship to study genetic changes on the Y (male) chromosome, with the goal of explaining why boys are four times more likely than girls to develop autism. His fellowship mentor is Stephen Scherer, PhD, director of the University of Toronto's McLaughlin Centre for Genomic Medicine and a member of Autism Speaks Scientific Advisory Board. Their work on autism genetics uses the revolutionary process of whole genome sequencing.

Last year was an exciting year for autism research, as we made strides in our understanding of autism’s underlying causes. Four research studies, each led by a different group of scientists, showed that there are likely to be hundreds of "autism genes." By autism genes, we mean genes where a change, or mutation, increases the risk that a person will develop autism.

The findings suggest that spontaneous mutations in these genes explain around 10 percent of autism cases. Spontaneous mutations occur in an egg or sperm, or very early in embryo development. They’re not present in either parent’s DNA. Such findings help explain why children with autism are often born into families not previously affected by the disorder.

In addition, two other studies identified new autism genes by looking into inherited mutations in close to 1,000 persons with autism. These inherited mutations were clearly passed down in a parent’s DNA. In all, they may contribute to the development of an additional 5 percent of the cases.

So why are we now finding so many genes? Thanks go primarily to improved technology – particularly “exome sequencing.” Any one person’s DNA is made up of around 3 billion pairs of “bases.” But only one percent or so of these base pairs make up functioning genes. We call this the “exome.”

When a mutation occurs, the change can involve one base pair – or up to a million of them! Older DNA technologies allowed us to look at the large mutations, those involving over 10,000 base pairs. Research showed that these mutations contributed to around 15 to 20 percent of the autism cases. Unfortunately, some of these large mutations affected several genes. We didn’t know which affected gene was the one causing autism.

Now we have exome sequencing. It allows us to look at single base mutations. These pinpoint changes that typically affect only one gene.

Researchers have now used exome sequencing to scan the DNA of close to 1,000 individuals affected by autism. We can now find out which genes are most often hit by single base mutations in these individuals. And these genes are those most likely to be the “autism genes.”

Not surprisingly, many of these genes turn out to have important functions in brain. But each one may have a different function than the others. These differences may explain why each autism “case” is so unique. Autism can result from many different combinations of genes – not to mention environmental influences that can affect gene function.

So what does all this “gee-whiz” science mean for families?

Genetic tests at the time of diagnosis – or soon after – can provide important treatment guidance. This is especially important in the case of gene changes linked to known syndromes with associated medical problems. Research is also rapidly advancing the day when an “autism gene panel” can help guide treatment of an individual’s autism symptoms.

Within families already affected by autism, gene tests can help clinicians and parents better understand risk in ways that encourage close monitoring and earlier diagnosis and intervention for younger siblings.  

Still, our discoveries to date leave a large portion of autism cases unexplained. There are likely many more genes, even other kinds of mutations to be identified and understood. We see our next big jump in discovery and understanding coming with whole genome sequencing. This technology allows us to look at all 3 billion base pairs in a person’s DNA! This is producing a tremendous amount of information. But we need to use whole genome sequencing with many more autism families to make sense of this information.

You and your family may be the key! Will you help us to fill in the puzzle? You can find out more about our studies here in Toronto here and here. You can find out more about participating in a broad range of autism studies here.

We also want to extend a sincere thank you to Autism Speaks and all its families and supporters for helping make our research possible.

Autism Speaks is funding a wealth of studies on the genetic and environmental factors involved in the development of autism. You can explore these and other studies using this website’s Grant Search.

Editor's note: For more perspective on real-life applications of this research, see this recent New York Times feature story on how whole genome sequencing is revolutionizing the diagnosis and treatment of disorders (including autism) that result from rare gene mutations.