Autism genes converge on asynchronous development of shared neuron classes.

ABSTRACT: Genetic risk for autism spectrum disorder (ASD) is associated with hundreds of genes spanning a wide range of biological functions^1-6. The alterations in the human brain resulting from mutations in these genes remain unclear. Furthermore, their phenotypic manifestation varies across individuals^7,8. Here we used organoid models of the human cerebral cortex to identify cell-type-specific developmental abnormalities that result from haploinsufficiency in three ASD risk genes-SUV420H1 (also known as KMT5B), ARID1B and CHD8-in multiple cell lines from different donors, using single-cell RNA-sequencing (scRNA-seq) analysis of more than 745,000 cells and proteomic analysis of individual organoids, to identify phenotypic convergence. Each of the three mutations confers asynch

SUBMITTER: Paulsen B 

PROVIDER: S-EPMC8852827 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature