We still don’t know the reason that causes autism, but observations from the fast developing field of epigenetics are contributing for revealing the subtle factors of the disorder.
Autism spectrum disorder (autism for short) is a term that describes many conditions, including problems with social communication, interaction with other people and repetitive/restrictive behaviors. It affects around 1 in 135 children under 7 years, and is 4 times more common in males than females.
We know that autism affects brain development, especially in the youth of an individual. And recent reports have shown us that the cause of the autism disorder is a fault in the genetic code.
But there is more to life than just a genetic sequence. Our genes, like the keys on a piano, are played differently in different individuals. This order in which genes are “played” makes our individual differences in health, even between identical twins.
We study the various “musicians” that tinkle the keys of our genome – the epigenetic influences that switch genes on and off and make every genotype unique. In real life, these are tiny molecules that are of key importance for making each tissue in our body different, despite the identical genes.
Our research team wanted to explore how autism is influenced by these epigenetic factors. First, we observed the genes whose sequences have already been linked with that disorder.
Thankfully, the Simons Foundation had already done this for us. They had even organized the genes by accumulated evidence for their contribution to autism.
Of the 16 genes that were most strongly suspected that cause autism, half code for proteins that influence how other genes work – the epigenetic musicians, as it were. Many of these genes also play a role in brain development.
Next we asked what is known about the physiology of people with autism. Among other things, it turns out that their immune systems are easier to be disrupted than those without autism. They are more likely to experience inflammation in the blood and the brain.
This may explain why immune suppressants have been shown to temporarily reduce some symptoms of autism.
Out Of Tune
We know that gene activity contributes much to the physiology of a person, but we also looked for studies that had measured gene activity in people with autism. Those genes most frequently “played” too loud or too quiet were connected to brain development and function and, again, with immune state in the blood and brain.
Finally, we took a look mostly on the epigenetic musicians that play the genes themselves. A few researchers had guessed which genes were not being played very well. Looking mostly in the brain, they found four or five genes whose musicians weren’t “playing” as they should’ve.
The clearest evidence was for the oxytocin receptor gene, for which two studies showed differences in the blood and brain of those with autism.
The “love hormone” or oxytocin regulates many of the behaviors associated with the disorder. Therefore, the level of oxytocin receptor is a plausible victim for causing some of the features that characterize autism.
The fastest way to search for genes associated with autism is to look everywhere in our genomes, and current technology is capable to achieve this. Therefore, we observed seven such genomes.
It wasn’t easy though, as different researchers have favorite techniques. What we had to do is reviewing three studies of the brain, three of blood and one of cheek cells. Yet again, genes involved in brain development and the immune system emerged on the top in all tissues studied.
To sniff out evidence for individual autism-associated genes, we searched for those identified by two independent studies. We had four genes as a result. It was a surprise that none had been indicated previously as autism-related. For two of these genes, we don’t actually know what they are responsible of in the body.
Of the other two, one is likely to take a part in the sense of smell. Interestingly, a common feature of autism is a lower sensory threshold –- senses, including smelling, work overtime.
The second gene codes for an epigenetic musician required for early development. Interestingly, this gene has its own epigenetic musicians switched in children whose mothers had low levels of folate during pregnancy. Even more connections were emerging, because low folate levels have also been associated with risk for autism.
Finding The Composers
So, what do we do with all this information? Firstly, as Aristotle said: “One swallow does not a summer make, nor one fine day.” This means that we need to find a lot more evidence to see whether epigenetic changes in such genes are truly responsible for autism.
We should also bear in mind the chance that such changes could result from autism rather than cause autism.
We are told by the information we gathered that researchers around the world should begin to give more attention to these candidate genes and epigenetic musicians. They should also focus more on biological processes, such as inflammation, that have not been identified from genetics alone.
But should we be thinking of ways to minimize inflammation during pregnancy to make the risk of autism? Should we choose low inflammatory environments as better for raising our children?
Furthermore, could these “melodies” of the epigenetic musicians be selectively edited to prevent or treat the symptoms of the autism disorder? There is currently insufficient data available for us to give an answer to these questions. But we are doing our best to listen carefully to the whole symphony to find out.