Long-read RNA-seq atlas of novel microglia isoforms elucidates disease-associated genetic regulation of splicing.

ABSTRACT: Microglia, the innate immune cells of the central nervous system, have been genetically implicated in multiple neurodegenerative diseases. We previously mapped the genetic regulation of gene expression and mRNA splicing in human microglia, identifying several loci where common genetic variants in microglia-specific regulatory elements explain disease risk loci identified by GWAS. However, identifying genetic effects on splicing has been challenging due to the use of short sequencing reads to identify causal isoforms. Here we present the isoform-centric microglia genomic atlas (isoMiGA) which leverages the power of long-read RNA-seq to identify 35,879 novel microglia isoforms. We show that the novel microglia isoforms are involved in stimulation response and brain region specificity. We the

SUBMITTER: Humphrey J 

PROVIDER: S-EPMC10705658 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature