The study reveals a new genetic mechanism behind the development of autism

Hospital scientists for sick children (sick) and the University of Las Vegas, Nevada (UNLV) have discovered a genetic link between autism spectrum disorder (TSA) and a rare genetic disease called type 1 myotonic dystrophy (DM1).

The study, published in Nature neurosciencesuggests that although the ASD has already been characterized by a loss of gene function, another mechanism can lead to social behavior often observed in people with ASD.

DM1 is a hereditary condition which causes progressive muscle loss and weakness. Although the TSA is present in around 1% of the general population, it is 14 times more likely to develop in people with DM1.

The study revealed that the genetic variation which causes repetition extensions DM1 – in tandem (very) in the DMPK gene – also has an impact on brain development. The research team found that the effects of the very interfere with a critical process called genetic splicing, which is essential for genetic function.

The disturbance causes protein imbalance which can lead to a diversion from several genes involved in the brain function and may explain why some of the social and behavioral results of TSA develop in people with DM1.

“Our results represent a new way of characterizing the genetic development of autism,” explains Dr. Ryan Yuen, the main scientist of the genetic and genome biology program at Sickkids.

“By identifying the molecular path behind this link, we can start studying new approaches to the diagnosis of TSA and the development of precision therapies that release these proteins in the genome.”

What are the very?

The very occurs when the sections of a bit of DNA are repeated twice or more, and the probability of these rehearsals causing errors of gene function increases each time.

In 2020, Yuen discovered that the very contributing to autism, identifying more than 2,588 different places in the genome where the TRE were much more widespread in people with ASD. Likewise, people with DM1 have a TRE in the DMPK gene.

“A variation really marked me that we see in rare neuromuscular diseases,” said Dr łukasz Sznajder, research manager and assistant teacher at the UNLV. “This is how we started to connect the points. We have found a molecular link, or overlap, which, in our view, is the heart of provoking it with autistic symptoms in children with myotonic dystrophy.”

Generating a key contributor to the development of TSA

While tandem rehearsal is developing in the DMPK gene, the research team, including collaborators from the University of Florida and Adam Mickiewicz University (Poland), noted that its altered RNA links a protein involved in the regulation of splicing genes during brain development.

This so-called “toxic RNA” deleates the protein and prevents it from binding to other RNA molecules in important areas of the genome, causing an imbalance of proteins which leads to a diversion of other genes.

“The very are like a sponge that absorbs all these important genome proteins. Without this protein, other areas of the genome do not work properly,” explains Yuen.

The Yuen Lab and the Sznajder Lab already explore if this diversion occurs in other genes associated with the TSA, as well as the way in which their results could shed light on the precision therapies that release these proteins in the genome.

Some of these works are already underway. In 2020, Dr. Christopher Pearson, principal scientist of the genetics and genome biology program of Sickkids, identified a molecule that can contract very in Huntington’s disease.

Although more research is necessary to identify how it could be applied to other conditions, the team remains optimistic, their results could shed light on research and future care for the DM1, the TSA and other conditions.