Northwestern Events Calendar


CAN SEMINAR SERIES: “Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD” with Dr. Michael Gandal

When: Thursday, November 9, 2023
2:00 PM - 3:00 PM CT

Where: Ward Building, 5-230, 303 E. Chicago Avenue, Chicago, IL 60611 map it

Audience: Faculty/Staff - Student - Post Docs/Docs - Graduate Students

Contact: Wesley Gryziak  

Group: Center for Autism and Neurodevelopment

Category: Lectures & Meetings


“Broad transcriptomic dysregulation occurs across the cerebral cortex in ASD”

Neuropsychiatric disorders classically lack defining brain pathologies, but recent work has demonstrated dysregulation at the molecular level, characterized by transcriptomic and epigenetic alterations. In autism spectrum disorder (ASD), this molecular pathology involves the upregulation of microglial, astrocyte and neural–immune genes, the downregulation of synaptic genes, and attenuation of gene-expression gradients in corte. However, whether these changes are limited to cortical association regions or are more widespread remains unknown. To address this issue, we performed RNA-sequencing analysis of 725 brain samples spanning 11 cortical areas from 112 post-mortem samples from individuals with ASD and neurotypical controls. We find widespread transcriptomic changes across the cortex in ASD, exhibiting an anterior-to-posterior gradient, with the greatest differences in primary visual cortex, coincident with an attenuation of the typical transcriptomic differences between cortical regions. Single-nucleus RNA-sequencing and methylation profiling demonstrate that this robust molecular signature reflects changes in cell-type-specific gene expression, particularly affecting excitatory neurons and glia. Both rare and common ASD-associated genetic variation converge within a downregulated co-expression module involving synaptic signalling, and common variation alone is enriched within a module of upregulated protein chaperone genes. These results highlight widespread molecular changes across the cerebral cortex in ASD, extending beyond association cortex to broadly involve primary sensory regions.

Thursday November 9, 2023
CAN Seminar Series 
2:00 PM - 3:00 PM
Location: Ward 5-230 

Dr. Michael Gandal 
Associate Professor of Psychiatry and Genetics
University of Pennsylvania

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