Related Experiment Video
Updated: May 14, 2026
11:20
Osmotic Avoidance in Caenorhabditis elegans: Synaptic Function of Two Genes, Orthologues of Human NRXN1 and NLGN1, as Candidates for Autism
Published on: December 11, 2009
Function and regulation of AUTS2, a gene implicated in autism and human evolution
Nir Oksenberg1, Laurie Stevison, Jeffrey D Wall
1Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.
Plos Genetics
|January 26, 2013
Summary
The AUTS2 gene is crucial for brain development and is linked to autism and other neurological disorders. Researchers identified key regulatory elements, or enhancers, that may explain how genetic changes in AUTS2 contribute to these conditions.
Area of Science:
- Neurogenetics
- Developmental Biology
- Evolutionary Genomics
Background:
- Nucleotide variations in the AUTS2 gene locus are associated with autism spectrum disorder (ASD) and various neurological conditions, including ADHD, epilepsy, and developmental delays.
- The AUTS2 gene harbors a significantly accelerated genomic region distinguishing humans from Neanderthals, primarily comprising noncoding variants, yet its function and regulation are poorly understood.
Purpose of the Study:
- To investigate the function of the AUTS2 gene in neurodevelopment.
- To identify and characterize regulatory elements (enhancers) of AUTS2.
- To explore the role of AUTS2 noncoding variants in neurological disorders and human evolution.
Main Methods:
- AUTS2 gene knockdown was performed in zebrafish to observe its effects on development and behavior.
- Enhancer activity assays were conducted in zebrafish and mice using candidate regulatory sequences.
- Assessed overlap of identified enhancers with ASD-associated deletions and human-accelerated regions.
Main Results:
- Zebrafish with reduced AUTS2 levels exhibited smaller head size, neuronal reduction, and decreased mobility, indicating its importance in neurodevelopment.
- Twenty-three functional enhancers were identified in zebrafish, with 10 showing brain activity.
- Three mouse brain enhancers overlapped an ASD-associated deletion, and four enhancers were located in human-accelerated regions, with two active in the brain.
Conclusions:
- AUTS2 plays a significant role in neurodevelopment.
- Identified candidate AUTS2 enhancer sequences are potential sites where nucleotide variations can lead to neurological diseases.
- These regulatory elements may contribute to human-specific traits and the evolution of the human brain.
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