Brand new mutations are helping scientists figure out what is going on in autism.

Autism is incredibly frustrating from a genetic point of view. Every study clearly shows that genetics plays an important role in this disease. But when these studies try to find a cause, they keep coming up short.

And this isn’t because scientists aren’t trying hard. They are. In most of the recent studies they are comparing thousands of people’s DNA at millions of different spots. If there was a simple explanation, they would have found it.

One thing they have managed to find from all of these studies is that a minority of cases result from brand new mutations that most likely happen in either the sperm or the egg before fertilization. While these are not going to be that useful as a diagnostic test, they may prove useful as a way of figuring out which genes to focus on. And maybe even for coming up with new ways to treat autism.

With that in mind, a whole slew of researchers set out to find more of these sorts of de novo mutations (as they are called). They reported their findings in the following three back to back to back reports in the journal Nature:

Study 1
Study 2
Study 3

These researchers took on the herculean task of looking at every letter of every gene of over two thousand people. Basically they compared the genes of parents to the genes of their autistic children (and a few of their unaffected siblings). They were able to confirm that some previously identified genes were important in autism and they identified a few new ones.

They were also able to confirm that older dads pass on more of these sorts of mutations than younger dads or moms of any age. Which makes sense if you think about sperm production.

Each time a sperm is made, its DNA needs to get copied. And each time DNA is copied, there is a chance for a mistake to creep in. So it makes sense that the older the dad, the more mutations he’ll have in his sperm.

Frustratingly, this was the most solid finding in the study. But fret not. They also learned some important things about how autism happens too.

The most important thing they found was that many children with autism shared mutations in related genes. Their mutations affected different genes that all impacted the same or related biochemical pathways.

An fMRI scan of an autistic brain.

This is what we might expect from something as complicated as brain development. To pull off something like this, various genes are going to need to fire off at the right time in the right order. If any one of the genes in a similar pathway misfires, you can end up with similar problems. And this is undoubtedly happening in some cases of autism.

This is a very important finding for identifying where to focus research so new treatments can be found for this disease. Isolated genes can be hard to target because sometimes scientists don’t know what they are doing or how they fit into the grand scheme of things. But researchers can identify a pathway, then they can identify chemicals that can tweak that pathway that can one day become medicines.

These studies also highlight yet again what a hideously complex disease autism is. Your risk depends on what versions of lots of different genes you have. Some versions will increase your risk and some will decrease it. Your chances are a summation of all of these risks.

As if this wasn’t complicated enough, autism is more than genes. Something in the environment has to trigger the disease and we know very little about these triggers (except that vaccines aren’t one). Now add to this the fact that different genetic combinations are going to be susceptible to different triggers and you begin to see why this has been such a challenge to geneticists.

Figuring out why a particular person ended up with autism is really hard. But even if we can’t figure it out for a particular person, these studies are important for finding what is happening in the brains of people with autism. And hopefully by knowing that, we can find new treatments.



A long video about the biology of autism. Well worth your time.

Desperately Seeking Autism Genes 3 May,2012Dr. Barry Starr

Author

Dr. Barry Starr

Dr. Barry Starr (@geneticsboy) is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA and runs their Stanford at The Tech program. The program is part of an ongoing collaboration between the Stanford Department of Genetics and The Tech Museum of Innovation. Together these two partners created the Genetics: Technology with a Twist exhibition.

You can also see additional posts by Barry at KQED Science, and read his previous contributions to QUEST, a project dedicated to exploring the Science of Sustainability.

Sponsored by

Become a KQED sponsor