COOKIES: By using this website you agree that we can place Google Analytics Cookies on your device for performance monitoring. |
University of Cambridge > Talks.cam > Making connections- brains and other complex systems > Broad Transcriptomic Dysregulation Occurs Across the Cortex in ASD
Broad Transcriptomic Dysregulation Occurs Across the Cortex in ASDAdd to your list(s) Download to your calendar using vCal
If you have a question about this talk, please contact Sofia Orellana. 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 cortex. 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. This talk is part of the Making connections- brains and other complex systems series. This talk is included in these lists:
Note that ex-directory lists are not shown. |
Other listsCambridge Neurological Society Philosophy of Physics mig40's listOther talksMelville Lecture 2023: “Topometric Design of Self-Assembled Biomimetic Composites” An overview of the CASS group at Imperial Common Forms of Obesity & Fat Distribution, From Phenotypes to Mechanisms hIPPYlib-MUQ: A Bayesian Inference Software Framework for Integration of Data with Complex Predictive Models under Uncertainty Shallow water modelling of rainfall-runoff processes Uniqueness and support theorems for analytic double fibration transforms |