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

  • Tonybateson

    Of coourse it is extremely difficult to find an environmental cause for autism when an enormous barrage of dollars is directed towards frustrating that search. For my small part I have relentlessly searched for autistic people who are not vaccinated without ever finding one who is unequivocally so. I do not mean just amongst my neighboours and acquaintances I mean amongst hundreds of autistic families I know (I was Vice Chairman of the UK National Autistic Society and knew hundreds) and as a prolific writer, broadcaster and website owner, I made contact with thousands. Just where are the unvaccinated? There should be around fifty thousand in the UK if vaccination is neutral to autism as the Department for Health once said. But they don’t seem to say it any more and I still haven’t found one sixteen years after I first started looking in 1996. Where are they? and how many environmental triggers do we have to look for before the realisation hits someone?

    Tony Bateson, Cheltenham, UK.

    • John Fiorentino

      Well Tony…..It seems science is willing to concede a correlation between vaccination and encephalopathy, just not to autism. It certainly appears further research is indicated.

  • Barry

    That’s an interesting point. How many children are unvaccinated in Britain?

    • Sissijanov

      Most interesting is that in that large group there is no autism…if there were the vaccine refusers would become smaller in number..something needs to be addressed here..

      • Barry

        I think it is important to say that unvaccinated kids do get autism. The study I cited in a previous comment definitely shows that. The question is whether unvaccinated kids have lower rates of autism. This question is still up in the air.

        • Sissijanov

          oh yes, the numbers, no one wants to study those numbers..when the cdc did their most recent count did they deliberately avoid including that information…the unvaccinated victims are likely a small percentage or as I suggested..mothers would not refuse vaccines if they saw within their families and communities anything other than a direct connection between autism and vaccines and a more well group of non vaccinated children

          • Barry

            The number of unvaccinated children in the U.S. is very small. Something like 3 in 1000. This is probably a small enough number that you’d need to design a survey that looks specifically at that group to get meaningful numbers. In other words, it might be hard to tease those numbers out of a more general autism study.

  • Leigh Anne Uribe

    A good article, except for the one line “we know very little about these triggers (except that vaccines aren’t one).” When was this unequivocally proved? My personal theory is that autism is a sort of immune response disorder and I do not believe that injecting newborns with up to 7 or 8 vaccines at once, which most doctors recommend, without understanding how a person’s individual immune system can handle that amount of stimulation is dangerous until proven otherwise. Possibly this vaccine schedule is safe for the majority but for those with sensitive immune systems, it may prove disastrous. I wish that I would see someone working on this type of study. In other words, I do not think that individual vaccines are dangerous, but I do think that this schedule of injecting 5-7 vaccines at one time into a tiny human which most Americans follow may be foolhardy.

  • Barry

    Thanks! I put that in because it usually serves as a great way to get discussions started. And it turns out that the studies done thus far bear it out.

    Yours is an interesting idea though. I am trying to think of the best way to conduct such a study AND to get kids the vaccines they need. I suppose you could try a different vaccine regimen and see if it decreases the cases of autism compared to a control group that received the usual regimen. To do such a study, you’d need some evidence to support your idea. Are there countries that do vaccinations differently that have fewer cases of autism?

  • John Fiorentino

    Good article Barry!

    I’m posting an abstract of an article here which you may like to read (if you haven’t already) and I sent a pdf full version to you by e-mail.


    John F.

    Theoretical aspects of autism: Causes—A review

    Helen V. Ratajczak

    Autism, a member of the pervasive developmental disorders (PDDs), has been increasing dramatically since its
    description by Leo Kanner in 1943. First estimated to occur in 4 to 5 per 10,000 children, the incidence of autism
    is now 1 per 110 in the United States, and 1 per 64 in the United Kingdom, with similar incidences throughout the
    world. Searching information from 1943 to the present in PubMed and Ovid Medline databases, this review summarizes
    results that correlate the timing of changes in incidence with environmental changes. Autism could result
    from more than one cause, with different manifestations in different individuals that share common symptoms.
    Documented causes of autism include genetic mutations and/or deletions, viral infections, and encephalitis following
    vaccination. Therefore, autism is the result of genetic defects and/or inflammation of the brain. The inflammation
    could be caused by a defective placenta, immature blood-brain barrier, the immune response of the mother
    to infection while pregnant, a premature birth, encephalitis in the child after birth, or a toxic environment.

    • Barry

      Thanks John! I did miss that one but it is on my list to read this week. I’ll let you know what I think.

  • Tonybateson

    The humber of children unvaccinated in the UK has fuctuated greatly since records started to be kept in 1966 by the Office of the Government Chemist or something like that followed by the Health Protection Agency. As the annual birthrate is between 600,000 and 700,000 even a ten percent unvaccinated figure (probably conservative) would have generated almost 3 millions of unvaccinated individuals. What’s the prevalence of autism in this number please?

    Tony Bateson, Cheltenham, UK

    • Barry

      I haven’t seen any studies on this subject but it seems the results would be interesting either way. There was an internet survey done but it was not very useful for a lot of reasons. The one at is more promising although it is difficult to know how reliable it is since it did not result in a peer reviewed paper.

      I think you could probably get the CDC behind it if the intent was to determine if the current schedule of vaccines leads to increased risk of autism (unvaccinated kids do get autism after all). Then the remedy would not be to eliminate vaccines which would be a nightmare for world health but to change the scheduling to better balance the risks.

      • Barry

        PS Of course we need to be careful of who did the survey I linked to…they seem fairly anti-vaccine.

  • Jen

    Am I the only one who takes offensive to calling autism a “disease”? Love the post except for that reference. Disease suggests that there is something inherently wrong with autism. In general it is a spectrum ranging from severe autism to functioning asperger’s syndrome.

    Though it looks different from what people are used to, it is often accepted as a different way of thinking by the autistic community. They accept that though social skills can be learned, the way of thinking is there for life, as if it an integral part of their personality. Many people in the community would take offense to the suggestion that it can be cured, as the reference as a disease suggests.

    Take for example such public figures as Bill Gates and Einstein, who are speculated to have had some form of Autism Spectrum Disorder. Would you suggest to “cure” them of the “disease” they have that causes them to shun interpersonal relations and instead search for mathematical and scientific innovation? What kind of society would we be without major advances in computers, science and mathematics by people as dedicated as those with autistic traits?

    Sorry to be nitpicky about it, as I’m sure many people would interchange disease and disorder when it comes to autism, but I just wanted to advocate for the underdog.

    • Barry

      You were totally right in calling me on that. I am usually very careful about these sorts of labels (I try to refer to autism as a condition rather than a disease) but I slipped up. As I was writing this I was thinking more of the very severe cases of autism that can be crippling enough to qualify as a disease.

  • @Jen I am sick of all this autism madness, so no, you are not the only one…. if something else changes in people, it is just evolution, but here, they tend to MUST HAVE control over everything because THEY call it a disease and THEY can’t handle it… although they should just accept that this is evolution and nature will deal with it and make its own selections…. I’ll tell you even what… if they would find a treatment (how they call it) I would never take it… I am me and I don’t feel the need to change…. but I would also force them to learn how to deal with people who are different instead of pretending that they are the way how it should be, I think they need a cure for a better understanding and acceptation of differences, not me… I have nothing more to say.

  • Pingback: Look to your left, Mr. Bateson | The Poxes Blog()

  • Laura Lam

    Why do you call autism a disease? Autism is NOT A DISEASE!! Please edit (or change) it!


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.

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