Study identifies single gene behind gene network linked to autism

Griffith University researchershaveidentified a single gene that regulates a network of genes linked to causing autism and intellectual disability.

The findings are the culmination of a three-year project conducted by the Griffith Institute for Drug Discovery’s (GRIDD) Associate Professor Stephen Wood, along with Griffith graduates MariaKashermanand Susitha Premarathne.

The team worked in collaboration with researchers from the University of Chicago, Northwestern University, University of Queensland and University of Adelaide.

‘Usp9X Controls Ankyrin-Repeat Domain Protein Homeostasis during Dendritic Spine Development’ has been published in Neuron.

The study revealed that a gene called USP9X regulated a network of proteins (called ANKRDs) that modify cell structures that regulate how nerves communicate with one another and interpret information.

This research defined a critical period of early postnatal brain development where USP9X regulation of ANKRDs was critical to normal function. Mutations in the ANKRD genes are associated with intellectual disability and Autism Spectrum Disorder but also bipolar disorder and schizophrenia.

“Currently there are over 1000 genes associated with neurodevelopmental disorders such as intellectual disability and autism,”Associate Professor Stephen Wood said.

“The economic cost of these disorders can rival that of diseases such as cancer, due to their prevalence and the fact that they are lifelong afflictions.

“In the past, the research focus has been on identifying individual gene mutations. Now, we are looking at finding networks of genes and ‘gene hubs’, which mutated genes interact with or pass through.”

With this new knowledge of USP9X, researchers believe thereis now the possibility of developing treatments for thegene mutation.

This work extends studies previously performed by the research team, members of whom were part of a research project that first discovered USP9X’s role in brain development and links to intellectual disability and autism.

The study was conducted in vitro with the hope thatmodel would be developed further totest interventions in mice as a step toward therapeutic approaches in patients.


This work was supported by R01MH107182 to P.P. We thank NU Nikon Cell Imaging Facility for use of the N-SIM. Protein expression and purification was performed in the Recombinant Protein Production Core Facility at North- western University. Special thanks go to SergiiPshenychnyifor assistance throughout.In vitroanalyses were performed in the Analytical Bio-NanoTechnologyCore Facility of the Simpson Querrey Institute at North- western University. Northwestern University provided funding to develop this facility and ongoing support is being received from the Soft and Hybrid Nano-technology Experimental (SHyNE) Resource (NSF NNCI-1542205). Molecular modeling was performed by the Medicinal and Synthetic Chemistry Core at Northwestern University. The authors declare no competing interests.