PUBLICATION

Function and Regulation of AUTS2, a Gene Implicated in Autism and Human Evolution

Authors
Oksenberg, N., Stevison, L., Wall, J.D., and Ahituv, N.
ID
ZDB-PUB-130201-20
Date
2013
Source
PLoS Genetics   9(1): e1003221 (Journal)
Registered Authors
Ahituv, Nadav
Keywords
Zebrafish, Midbrain, Motor neurons, Eyes, Embryos, Mice, Phenotypes, Hindbrain
MeSH Terms
  • Animals
  • Autistic Disorder*/genetics
  • Autistic Disorder*/metabolism
  • Base Sequence
  • Biological Evolution*
  • Enhancer Elements, Genetic/genetics*
  • Genomics
  • Head/pathology
  • Humans
  • Mice
  • Neanderthals/genetics
  • Neurons/pathology
  • Phenotype
  • Proteins*/genetics
  • Zebrafish/genetics
PubMed
23349641 Full text @ PLoS Genet.
Abstract

Nucleotide changes in the AUTS2 locus, some of which affect only noncoding regions, are associated with autism and other neurological disorders, including attention deficit hyperactivity disorder, epilepsy, dyslexia, motor delay, language delay, visual impairment, microcephaly, and alcohol consumption. In addition, AUTS2 contains the most significantly accelerated genomic region differentiating humans from Neanderthals, which is primarily composed of noncoding variants. However, the function and regulation of this gene remain largely unknown. To characterize auts2 function, we knocked it down in zebrafish, leading to a smaller head size, neuronal reduction, and decreased mobility. To characterize AUTS2 regulatory elements, we tested sequences for enhancer activity in zebrafish and mice. We identified 23 functional zebrafish enhancers, 10 of which were active in the brain. Our mouse enhancer assays characterized three mouse brain enhancers that overlap an ASD–associated deletion and four mouse enhancers that reside in regions implicated in human evolution, two of which are active in the brain. Combined, our results show that AUTS2 is important for neurodevelopment and expose candidate enhancer sequences in which nucleotide variation could lead to neurological disease and human-specific traits.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping