Last updated January 18, 2018 at 3:42 pm
Autism spectrum disorder has no known cause. Studies have shown that genetics and environmental factors, such as complications during pregnancy, may play a part in developing autism. But a specific cause has yet to be found.
Researchers have started to use an epigenetic approach to try to find what could be happening to our genes that would relate to autism.
A new study published today found more than 2000 regulatory regions (DNA regions that control gene expression) involved in learning that are strongly associated with autism. Within their findings, they identified a genetic mutation in one of these regions that is associated with increased risk of autism.
Epigenetics adds another layer to understanding genetics
Epigenetics looks at factors that control gene expression such as chemical modifications of DNA and the proteins that are created from those genes. The epigenome cause changes and can influence gene expression without changing our DNA sequence.
We have one genome, our DNA, but the epigenome influences what proteins are created from an individual’s genes. Now, what those epigenetic changes are are unique to individuals, but they can be passed on from our mother, and recent evidence is also suggesting the father. Certain lifestyle aka environmental factors are known to be able to change our epigenome.
Regulatory regions associated with autism identified
It is known that learning and long-term memory formation requires epigenetic regulation. To identify regulatory regions associated with autism, they hypothesised that the same regulatory regions involved in learning and memory may also be linked to autism.
Using a mouse model, researchers set up an experiment to determine learning-induced changes. Mice were placed in a box and given a small shock. When placed in the same box after 24 hours, they mice had learned to associate the box with the box and would freeze. The researchers analysed DNA from the hippocampus in the brain, an area linked to memory, to see if there were any epigenetic changes in the form of chromatin accessibility.
Chromatin helps package the long strands of DNA to tightly coil it so it can fit inside cells. As it unwinds, and closes again, it can control access to certain genes during transcription, which is the first step in creating proteins from DNA.
They found that learning increases chromatin accessibility at specific places in the genome.
To determine the regions where these epigenetic changes were occurring, the researchers repeated the experiment and analysed the data for gene expression levels. They found 2,365 regions regulated by learning.
They looked for genes near these identified regulatory regions and found many of them were known genes associated with autism spectrum disorder.
The researchers went further. Using a known autism risk gene, Shank3, they looked for a genetic risk factor in the regulatory regions for these genes. They found a genetic mutation, that they crossed with genomic data from a clinical study of 554 children with autism and 214 healthy controls to confirm that it was associated with autism spectrum disorder.
Greater understanding of autism in future
Autism spectrum disorder affects about 1 in 100 Australians. Despite how common it is, understanding autism would help families and individuals with autism to have a better quality of life.
Whilst one of the most common hallmarks in autism are learning difficulties, there are other behaviours associated within the autism spectrum. This study opens the potential for others to look for mutations in regulatory regions associated with those behaviours.
Together this information could be pooled together to help with accelerated diagnoses, better predictions of severity, improved intervention methods, and even treatments.
It is hoped that further investigations into epigenetics “may eventually lead to improvements in the diagnosis and treatment of autism,” according to study co-author Lucia Peixoto, an assistant professor in the WSU Elson S. Floyd College of Medicine.
This research was published in Science Signaling.