Over 200 genes linked to autism identified- Here’s all you need to know

Toronto: Researchers have unravelled a network of more than 200 genes linked to autism, an advance that will help develop new therapies for the common neurological disorder that is estimated to affect one in 160 children worldwide. The new genes were involved in controlling alternative splicing events that are often disrupted in autism spectrum disorder (ASD).  Alternative splicing is a process that functionally diversifies protein molecules — cells’ building blocks — in the brain and other parts of the body. 

The researchers had previously showed that disruption of this process is closely linked to altered brain wiring and behaviour found in autism. “Our study has revealed a mechanism underlying the splicing of very short coding segments found in genes with genetic links to autism,” said Benjamin Blencowe, Professor at the University of Toronto’s Donnelly Centre. 

“This new knowledge is providing insight into possible ways of targeting this mechanism for therapeutic applications,” Blencowe added in the paper described in the journal Molecular Cell. 

Best known for its effects on social behaviour, autism is thought to be caused by mishaps in brain wiring laid down during embryo development.  Hundreds of genes have been linked to autism, making its genetic basis difficult to untangle. Alternative splicing of small gene fragments, or microexons, has emerged as a rare, unifying concept in the molecular basis of autism.

To better decode it, the team used gene editing tool CRISPR and removed each of the 20,000 genes in the genome of cultured brain cells to find out which ones are required for microexon splicing. 

They then identified 233 genes whose diverse roles suggest that microexons are regulated by a wide network of cellular components. Knowing the precise molecular mechanisms of microexon splicing will help guide future efforts to develop potential therapeutics for autism and other disorders. 

For example, because the splicing of microexons is disrupted in autism, researchers could look for drugs capable of restoring their levels to those seen in unaffected individuals.