Cell-type-specific effects of autism-associated chromosome 15q11.2-13.1 duplications in human brain.

A recent study examined the effects of a specific genetic duplication, known as 15q11.2-13.1, on gene expression and chromatin accessibility in different cell types in the human brain. The duplication is associated with an increased risk of autism spectrum disorder (ASD). The researchers conducted single-nucleus RNA-sequencing and multi-omic sequencing on individuals with the duplication, individuals with ASD but without the duplication, and neurotypical controls. They found that the effects of the duplication on gene expression and chromatin accessibility varied across different cell types, with neuronal subtypes showing the greatest upregulation of gene expression. The study also identified distinct transcriptional regulatory motifs implicated in ASD and the duplication, suggesting different biological mechanisms. These findings have implications for therapeutic development in individuals with the duplication and for understanding the effects of copy number variations in neurodevelopmental disorders more broadly. [Extracted from the article]