The Smallest Gene Segments May Play a Big Role in Autism Spectrum Disorder

The Smallest Gene Segments May Play a Big Role in Autism Spectrum Disorder

Posted: March 9, 2015

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New research sheds light on the big potential impact in neurological and psychiatric disorders––including autism spectrum disorder (ASD)––of very small bits of our genome called microexons.

Microexons are the smallest type of gene segments that actually “code,” or give instructions for, the creation of proteins.  (Most of the genome has other purposes and is not involved in generating proteins.) In a study published this past December 18th in Cell, a research team found that patterns of irregularities in microexons were associated with ASD and, more broadly, with processes in the brain that are implicated in other disorders.

The team, led by Benjamin Blencowe, Ph.D., of the University of Toronto, assessed microexons in postmortem brain samples from both mice and people. For the first time, they showed that microexons involved in encoding proteins were especially irregular within specific brain regions of people with ASD. Among people with ASD, the team further detected improperly regulated microexons within genes that have previously been linked to intellectual disability. These results point to specific microexon irregularities as part of the pathology of ASD. Some of these irregularities may contribute to cognitive deficits associated with the condition.

The team, which included Daniel H. Geschwind, M.D., Ph.D., 2012 recipient of the Foundation’s Ruane Prize for Child and Adolescent Research, also found that one particular microexon influences interactions between proteins that affect two important processes in the brain. One process is synaptic plasticity, the capacity of connections in the brain to change over time. The other process is neurite outgrowth, the thread-like projections brain cells extend to connect with other neurons. Disruptions in both of these processes have been linked to neurological disorders, including ASD.

The new findings are consistent with previous work associating particular microexons with ASD, schizophrenia, and epilepsy. It may be the case, the researchers say, that the disrupted regulation of microexons ultimately contributes to ASD and other disorders by interfering with protein-interaction networks that are needed for healthy development and function of brain cells, a possibility open for future study.

Read the abstract.