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
AUG 04, 2021
Clinical & Molecular DX
Fear of Smells Could Help Diagnose Migraines in Kids
AUG 04, 2021
Fear of Smells Could Help Diagnose Migraines in Kids
  A new study suggests the intense dislike of pungent smells and odors could be a diagnostic marker for migraines a ...
SEP 21, 2021
Clinical & Molecular DX
Kidney Failure in COVID Survivors
SEP 21, 2021
Kidney Failure in COVID Survivors
New findings indicate that individuals who survive COVID-19 infections, even mild ones, have a significantly elevated ri ...
OCT 27, 2021
Microbiology
Think Outside the Box to Reduce Waste, Improve Productivity
OCT 27, 2021
Think Outside the Box to Reduce Waste, Improve Productivity
Are you looking for ways to streamline your prepared media delivery and inventory stock management systems in your micro ...
NOV 04, 2021
Clinical & Molecular DX
Tech Offers a Brighter Tomorrow for Difficult-To-Treat Epilepsy Patients
NOV 04, 2021
Tech Offers a Brighter Tomorrow for Difficult-To-Treat Epilepsy Patients
It's difficult for neurologists to predict which patients living with epilepsy will respond to anti-seizure medicine ...
NOV 02, 2021
Technology
Mini Sensors Help Detect Neuromotor Abnormalities in Infants
NOV 02, 2021
Mini Sensors Help Detect Neuromotor Abnormalities in Infants
Neuromotor abnormalities (such as abnormal movement and gross motor abilities) are often caused by often unseen damage t ...
NOV 15, 2021
Cancer
Dogs Get Cancer Too
NOV 15, 2021
Dogs Get Cancer Too
“Cancer” isn’t a word anyone wants to hear from their doctor. However, many dog owners may not conside ...
Loading Comments...