Home > Science > Gene expression in the brain reveals surprising similarities and differences

Gene expression in the brain reveals surprising similarities and differences

Autism is a very heterogeneous disorder. As the grand lady of neurology, Dr. Isabelle Rapin liked to emphasize when training new students “If you have seen one child with autism, you have seen one child with autism.” This heterogeneity has made understanding causes and designing effective treatments more challenging than it would be otherwise.

However, a new study published this week in Nature and supported by Autism Speaks’ Autism Tissue Program and Autism Genome Project reveals that the heterogeneity may not be as problematic as it initially seems. Differences in common molecular pathways appear to underlie the pathology in the brains of individuals with ASD.

Daniel Geschwind, M.D., Ph.D. (UCLA) launched an ambitious study to examine not just the variants of genes that may confer risk for autism, but the interaction with those genes and proteins working to support brain function. Looking for patterns of interaction in the brain, Dr. Geschwind and his colleagues sought to characterize the transcriptome – the set of fragments of instructions, called RNA, read from the gene DNA on the path to making functional proteins.  Importantly, unlike the gene DNA that is relatively fixed for an individual’s life, the RNA transcriptome is modified through experience and interaction with the environment.

The authors analyzed patterns of expression of RNA for three areas of the post-mortem brain tissue from individuals with ASD or typically-developing individuals. Two areas of the late-developing cerebral cortex (prefrontal cortex and the superior temporal gyrus) and a region of the cerbellum known as the vermis were compared between the autism and typically developed brain tissue. The first big surprise was that although the cortex transcriptome revealed over 400 different genes with different expression between the autism and typical brain tissue samples, the similar comparison in the cerebellar transcriptome revealed exactly two differently expressed genes. Whatever differences exist in the brains of individuals with autism, these differences are greatest in the instructions that guide the structure and function of the cerebral cortex.

This, however, was just the beginning of what the research team found. Imagine the cerebral cortex of brain is like a bustling metropolis – one part of the city develops into a residential area and the other becomes a business district. Both neighborhoods have very distinctive features that make them unique due in part to the time and manner in which they developed and the people who inhabit them. So too for different regions of the typically-developing cerebral cortex.  Different regions of the cortex develop at different times and with different inputs from the environment. The prefrontal cortex is one of the late-developing regions in the infant brain. Different regions also serve different functions, like integrating information from sight, sound and touch in the case of the superior temporal gyrus, and higher cognitive functions in the prefrontal cortex.

Importantly for Dr. Geschwind and his colleagues, these two cortical regions also have their own unique pattern of expression in brains from typically developed individuals. However, when looking for these unique signatures, the research team instead found surprisingly similar patterns of gene expression across the two regions in the brains of people with autism. Referring back to the metropolis analogy, in the autism brain samples, the residential and business districts are more alike than they ought to be.

There were also differences in expression of two gene networks between the autism and control brain samples. The first network of genes encodes synaptic function. This is reassuring because most of the autism risk genes identified through previous studies focused on synaptic function. The second network of differential gene expression was related to immune function and inflammation. This too harkens back to previous studies showing inflammation and immune system activation in the brains of individuals with autism. This gene network does not correlate with the results of large gene association studies like the synaptic network, indicating that secondary or environmental effects are involved in stimulating the observed inflammatory markers.

“This is the first study to show differences in the patterns of gene expression between brain regions, said Rob Ring, Ph.D., Autism Speaks vice president for translational research. “It’s those patterns of gene expression that enable the brain to function normally and to communicate properly with other regions of the brain.”

Taken together, these results have quite an impact on how we understand autism. The similarity of gene expression across different regions of cerebral cortex in the brains of individuals with autism tells us that we should look closely at very early brain development as these patterns in cerebral cortex emerge. The same goes for the network of synaptic genes that are differentially regulated in individuals with autism. However, the differences observed in immune and inflammation gene networks are more likely to be related to secondary or environmental effects.  We must follow all the leads this research has provided if we are to make the next steps in developing supportive treatments and therapies for those living with autism spectrum disorders today.

  1. May 31, 2011 at 2:51 pm

    This is fascinating. Who wrote this blog item?

    • Leanne Chukoskie
      June 1, 2011 at 1:32 am

      Hi Jessica,

      I (Leanne Chukoskie, Ph.D., Science Editor and Writer for Autism Speaks) wrote this article. Sorry that we forgot the byline. I am trained in neuroscience (but not genetics) so I too found this research particularly fascinating. I believe that the identification of a brain-based gene expression pathway due to likely environmental influences is a novel finding and definitely worth a shout-out.


  2. Norma
    May 31, 2011 at 4:07 pm

    This is so interesting. I have two adult sons with Asperger’s. Since their diagnosis’ years ago, there has been an ever growing fascination with this subject and I am still learning. Years ago, it seemed no one understood nor really touched this topic. Thank you so much for posting.

  3. Katie Wright
    May 31, 2011 at 4:11 pm

    I don’t understand what is new here?
    Isn’t this just describing how autism alters the brian – after the fact it has been altered?
    Like most ASD Moms I gave birth to a healthy baby. He was alert, affectionate, talkative and then was – gone- within a few months.
    My son suffered horrific brain damage after days of high fevers and febrile seizures.
    I already understand how his brain was altered – why aren’t we studying the obvious environmental factors preceding the brain damage?

    We have already known for many YEARS that ASD is intricately connected to inflammation and that those w/ family histories of autoimmune disorders are at high risk for adverse vaccine reactions and regressive autism.

    Let’s do something about this in terms of prevention.

    • Kimberly
      May 31, 2011 at 9:22 pm

      Not every child with Autism just suddenly seems to become Autistic, though. My son was always different, since he was a baby. He was always late with his milestones, he had to be taught to roll over, to sit up, he’s always had sensory issues with certain clothes, blankets, and other textures, just to name a few things. Therefore, in my son’s case, it was obviously NOT vaccines. They found micro deletions on two of his chromosomes that have been linked to Autism. I am not saying that you are wrong by any means. I think there are many different causes and triggers and you are absolutely correct in saying that they need to do something preventive as well.

  4. Noreen
    May 31, 2011 at 5:33 pm

    @Katie – Because they are FINALLY listening! It took some stupid Lawsuit win for them to FINALLY listen to the fact that these vaccines (what will effect a body more than INJECTING IT with neurotoxins, mercury, aluminum, Live virus’, etc.). After watching these healthy teens suffer after the HPV and having Dr.’s sue because the FLU vaccine injured them, and AUTISM rates at an all time high!!!! What does it take to HAVE the Medical and Health Community make a difference TAKE ACTION to prevent Autism. #1 Stop recommending Flu shots to PREGNANT WOMEN. #2 the DPT shot needs to be broken UP #3 and YES this is going to Effect Greedy People’s Stock HOLD PEOPLE ACCOUNTABLE FOR CAUSING BABIES BRAIN DAMAGE AND DEVELOPMENTAL DIFFICULTIES or at MINIMUM Government must SUPPORT them and TAKE ACTION to minimize the TOXINS INJECT into a brain that is DOUBLING in size. I understand that Autism comes in different ways (maybe 4 different) but INJECTING THE BABY with Sexually Transmitted Hep B 24 hours after BIRTH. You’re Bleepping NUTS and you don’t INFORM People. You SUCK Government. You’re hurting our generations to come and you need to be MORE PROACTIVE and Protective OF YOUR OWN OFFSPRING. Wake UP!!!! Already

  5. Katie Wright
    June 1, 2011 at 8:53 am

    I agree w/ you Kimberly that autism comes in different forms and has different causes.

    I am just saying that continuing to study genes in isolation of the environment is a fruitless endeavor. We cannot change our genes. That is why we need to stop funding genetic and brain research at a 10:1 ratio over environmental and biomedical research. And let’s stop talking about the obvious and do novel research on environmental triggers. It wasn’t news that the immune system and inflammation were involved in ASD 5 yrs ago!

  6. June 10, 2011 at 1:54 pm

    I don’t think autism is an evironmental cause that’s gotten worse due to vaccines, industrial-living areas, etc.. My cousin has autism and he was born in 1963. His mother and mine are identical twins. I’m not autistic, but my daughter is. I think we should concentrate on a cause that’s been around for decades, not just the past few years, as everyone seems to think. I read something that now it’s believed that SSRI antidepressants taken while pregnant, and/or having gestational diabetes causes autism in offspring…come on, get real! Is this just a way to keep our dollars flowing into autism research? Look at genes and families…that’s my advise

  1. August 8, 2011 at 3:54 am

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