Scientists have discovered a gene that may be responsible for defining behaviors linked to autism.
As autism now affects one in 31 American children – a stark increase from one in 150 in the early 2000s – experts are searching for potential causes, ranging from better diagnostic criteria to pollution and medications.
Genetic factors also come into play, with about 100 genes and variations currently thought to be linked to autism spectrum disorder (ASD).
Now, researchers in Canada have pinpointed a gene on the X chromosome, a sex chromosome found in men and women, that may influence issues with social interaction and repetitive behaviors such as stimming.
They discovered that based on genetic data from nearly 10,000 people, dozens of deletions within the gene, dubbed PTCHD1-AS, were associated with an increased susceptibility of autism in males.
The experts believe this increased risk was specifically in men because men only have one X chromosome, while women have two.
Follow-up experiments in mice also showed male mice lacking the PTCHD1-AS gene showed changes in social behavior and repetitive actions.
The team believes the findings may pave the way to more targeted therapies to reduce the social and behavioral deficits found in autism.
Researchers in Canada have identified a gene that may be linked to social issues and repetitive behaviors in autism (stock image)
‘PTCHD1-AS gives us a new entry point to study the biology of ASD, sharpening our understanding of how specific biological pathways relate to key autism traits,’ Dr Stephen Scherer, senior study author and Chief of Research at The Hospital for Sick Children (SickKids) in Toronto, said.
‘This is essential, because no new therapeutics in clinical trials are designed to modulate the main features of ASD.’
The study, published in the journal Nature, looked at genetic sequencing data from 9,349 people with autism and 8,332 without the condition. Using that data, they searched for deletions along the X chromosome affecting the PTCHD1-AS gene.
They found 27 males with autism who carried PTCHD1-AS deletions from 23 unrelated families.
Their analysis showed deletions involving PTCHD1-AS were associated with a 2.6-fold increased risk of having autism compared to the neurotypical controls.
About 82 percent of the autistic individuals in the study had social difficulties, communication issues and repetitive behaviors like rocking back and forth, which led the team to believe PTCHD1-AS was linked to these autistic traits.
Additionally, the researchers looked at mouse models with PTCHD1-AS deletions and found that they spent significantly more time self-grooming than controls, which is considered a repetitive behavior. They also vocalized less and at a weaker intensity, signaling communication issues.
‘Our findings suggest there is a different biology involved with our PTCHD1-AS model compared to other ASD protein-coding models,’ Dr Lisa Bradley, first study author and research associate in The Centre for Applied Genomics at SickKids, said.
Based on mouse observations, the researchers found disrupting the PTCHD1-AS gene affected ‘synaptic plasticity,’ which is the brain’s ability to adapt and fine-tune signals in response to activity in the striatum, where repetitive behaviors are regulated.
‘When we examined gene and protein expression in this area, we saw changes in genes and proteins involved in regulating synaptic plasticity as well as myelination, the process that allows electrical signals to travel faster between neurons,’ Bradley said.
‘This gives us a molecular pattern we can use for future studies into the biological effect of this non-coding gene in the brain.’
The team also believes the gene reduces activity of protein kinase C in a brain circuit that connects the cortex to the striatum. Protein kinase C regulates synaptic plasticity, learning and memory.
‘Through a multi-disciplinary approach combining human genetics, mouse models, multi-omics and electrophysiology, we’ve connected a non-coding gene to measurable changes in brain function,’ Dr Graham Collingridge, senior investigator at Lunenfeld-Tanenbaum Research Institute, said.
‘Together, our research helps clarify how unique alterations in synaptic plasticity relate to the core features of autism.’
The team’s next steps involve looking more deeply at the pathways influenced by PTCHD1-AS to identify targets for future therapies.
‘Beyond significantly advancing our understanding of Autism as a human condition, the study shows how small changes in DNA can influence complex human behavior,’ Scherer said.
‘It’s amazing to me how much of our disposition is genetically “hardwired,” even in the traits that shape how we connect and interact.’
