DEC 31, 2020 6:00 AM PST

Silent Mice Drive Autism Gene Discovery

WRITTEN BY: Tara Fernandez

Around 1 in 54 children in the U.S. are diagnosed with autism spectrum disorder, or ASD, a broad range of conditions that include challenges associated with social skills, communication, and repetitive behaviors. This is not a single condition, but instead, a vast array of autism subtypes thought to be influenced by a complex interplay between genetic and environmental factors.

A recent study published in eLife details the discovery of a gene involved in ASD called KDM5A. This finding is particularly significant, given that experts estimate that many thousands of genetic mutations may be involved in ASD development. Until now, only around a third of cases have been linked to these known mutations. The work was led by Bruce Beutler, M.D., the 2011 Nobel Prize winner in Physiology or Medicine, awarded to him for his extensive work on the molecular basis of inflammation and infection.

"The difficult part in the beginning was finding the mutations. It had to be done by laborious cloning," explained Beutler.

"We developed a platform wherein when you see a phenotype you know the mutational cause at the same time." This technique, which links ASD-like behaviors in mice to a specific genetic root cause, has fast-tracked the search for genetic mutations in ASD.

In the study, Beutler and colleagues used an ASD mouse model in which genetic mutations were artificially introduced into the animals. The team studied how genetic alterations affected ASD development by tracking changes in how the mice communicated. The quality and number of vocalizations in mouse pups diminished with KDM5A mutations.

"Initially we found that the quality of these vocalizations was different in mice with KDM5A mutations. Looking more closely, we found that mice completely lacking KDM5A have a severe deficit in the number of these vocalizations," explained Maria Chahrour, a neuroscientist that led the study.

On top of being quieter than the control pups, these young mice also showed other trademark features of ASD symptoms: repetitive behaviors, difficulties learning, and less social interactions.

"We've identified a new genetic subtype of autism, and we're going to look for more patients with mutations in KDM5A," said Chahrour. "This has a direct impact on diagnosis too. When a clinician gets a clinical sequencing result that reports a KDM5A mutation, it's now a known autism gene."

Ongoing work is focused on further expanding the panel of ASD genetic biomarkers. "The wonderful thing about forward genetics is that we can grind away at the genome. We know progressively how much of the genome we've saturated," commented Beutler.

 

Sources: eLife, UT Southwestern.

About the Author
  • Tara Fernandez has a PhD in Cell Biology and has spent over a decade uncovering the molecular basis of diseases ranging from skin cancer to obesity and diabetes. She currently works on developing and marketing disruptive new technologies in the biotechnology industry. Her areas of interest include innovation in molecular diagnostics, cell therapies, and immunology. She actively participates in various science communication and public engagement initiatives to promote STEM in the community.
You May Also Like
FEB 09, 2021
Clinical & Molecular DX
Make Tissues Transparent to Spot Hidden Tumors, Let Machines Do the Rest
FEB 09, 2021
Make Tissues Transparent to Spot Hidden Tumors, Let Machines Do the Rest
A clearly defined border differentiates benign tumors from malignant ones. Malignant tumors start to get fuzzy around th ...
MAR 10, 2021
Clinical & Molecular DX
What's Your Type? Skin Microbes Linked to Dermatitis Severity.
MAR 10, 2021
What's Your Type? Skin Microbes Linked to Dermatitis Severity.
Microbiologists have discovered that the types of bacteria on a dermatitis patient’s skin affect the severity of t ...
APR 05, 2021
Clinical & Molecular DX
COVID Variants Can't Hide From CRISPR Diagnostic
APR 05, 2021
COVID Variants Can't Hide From CRISPR Diagnostic
New variants of the coronaviruses have emerged over the course of the pandemic through the natural evolutionary process ...
APR 27, 2021
Clinical & Molecular DX
No Batteries: Health Sensor Harvests Biomechanical Energy
APR 27, 2021
No Batteries: Health Sensor Harvests Biomechanical Energy
An international team of researchers has developed a wearable health monitor that works without the need for batteries. ...
MAY 09, 2021
Genetics & Genomics
Another Neurodevelopmental Disorder is Discovered
MAY 09, 2021
Another Neurodevelopmental Disorder is Discovered
Researchers are identifying more rare disorders because of advances in genetic sequencing technologies, which have made ...
MAY 15, 2021
Neuroscience
Eye Scans May Indicate Early Signs of Alzheimer's
MAY 15, 2021
Eye Scans May Indicate Early Signs of Alzheimer's
Researchers from the University of California San Francisco have found that retinal scans can detect changes in blood ve ...
Loading Comments...