Brain cell genomics reveals molecular pathology of autism

May 16, 2019

Molecular changes in specific types of neural cells and brain circuits correlate with the clinical severity of autism spectrum disorder, a new single-cell analysis of brain cells from autism patients finds. The results highlight what the authors refer to as autism-specific genes, or genes that represent high-priority targets for new therapeutic treatments for the disorder, though future studies involving larger patient cohorts are needed. Autism spectrum disorder (ASD), a developmental disorder encompassing a range of conditions and severities, affects 1 in 59 children in the U.S. and can impart social, communication and behavioral challenges. The genetic expression profile related to the disorder has been shown to widely vary. While hundreds of ASD susceptibility genes have been identified, none have been found to account for more than a small subset of cases. Despite the spectrum of clinical and genetic manifestations of autism, however, bulk gene expression studies have shown that the disorder affects cellular pathways and common genes. While related brain changes have been observed across autism patients, the specific cell types involved are unknown and have only recently become feasible to study. Dmitry Velmeshev and colleagues performed unbiased single-nuclease RNA sequencing to analyze the transcriptomes of single brain cells, including neurons and glia, from the brain tissue of patients affected with ASD. Studies in patients with epilepsy, often a co-morbidity of ASD, and in healthy people, helped confirm the genetic changes most closely associated with autism. Among the more than 100,000 single-nuclei gene expression profiles generated by the analysis, Velmeshev et al. discovered the pathways most affected by ASD were those that regulate synapse function as well as neuronal migration and outgrowth. What's more, the authors discovered that dysregulation of specific sets of genes expressed in upper-layer projection neurons correlate with the behavioral manifestations of ASD. Velmeshev et al. provide their dataset describing transcriptomic and ASD-associated gene expression changes across neuronal and glial cell types in an interactive web browser: https://cells.ucsc.edu/dev/?ds=autism.
-end-


American Association for the Advancement of Science

Related Autism Articles from Brightsurf:

Autism-cholesterol link
Study identifies genetic link between cholesterol alterations and autism.

National Autism Indicators Report: the connection between autism and financial hardship
A.J. Drexel Autism Institute released the 2020 National Autism Indicators Report highlighting the financial challenges facing households of children with autism spectrum disorder (ASD), including higher levels of poverty, material hardship and medical expenses.

Autism risk estimated at 3 to 5% for children whose parents have a sibling with autism
Roughly 3 to 5% of children with an aunt or uncle with autism spectrum disorder (ASD) can also be expected to have ASD, compared to about 1.5% of children in the general population, according to a study funded by the National Institutes of Health.

Adulthood with autism
The independence that comes with growing up can be scary for any teenager, but for young adults with autism spectrum disorder and their caregivers, the transition from adolescence to adulthood can seem particularly daunting.

Brain protein mutation from child with autism causes autism-like behavioral change in mice
A de novo gene mutation that encodes a brain protein in a child with autism has been placed into the brains of mice.

Autism and theory of mind
Theory of mind, or the ability to represent other people's minds as distinct from one's own, can be difficult for people with autism.

Potential biomarker for autism
A study of young children with autism spectrum disorder published in JNeurosci reveals altered brain waves compared to typically developing children during a motor control task.

Autism often associated with multiple new mutations
Most autism cases are in families with no previous history of the disorder.

State laws requiring autism coverage by private insurers led to increases in autism care
A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health has found that the enactment of state laws mandating coverage of autism spectrum disorder (ASD) was followed by sizable increases in insurer-covered ASD care and associated spending.

Autism's gender patterns
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.

Read More: Autism News and Autism Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.