Full-length isoform transcriptome of the developing human brain provides further insights into autism.

ABSTRACT: Alternative splicing plays an important role in brain development, but its global contribution to human neurodevelopmental diseases (NDDs) requires further investigation. Here we examine the relationships between splicing isoform expression in the brain and de novo loss-of-function mutations from individuals with NDDs. We analyze the full-length isoform transcriptome of the developing human brain and observe differentially expressed isoforms and isoform co-expression modules undetectable by gene-level analyses. These isoforms are enriched in loss-of-function mutations and microexons, are co-expressed with a unique set of partners, and have higher prenatal expression. We experimentally test the effect of splice-site mutations and demonstrate exon skipping in five NDD risk genes, including S

SUBMITTER: Chau KK 

PROVIDER: S-EPMC8437376 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature