Evolutionary hotspots of structural variation drive inter-individual differences in the expression of fusion transcripts in the human brain.

ABSTRACT: Alternative splicing is a well-known contributor to transcriptomic diversity between individuals. Less explored are inter-gene splicing events, which generate fusion transcripts-RNA molecules combining exons from two or more distinct genes. In cancer, fusion transcripts frequently result from somatic structural rearrangements, yet it remains unclear to what extent germline structural variants in non-cancer tissues contribute to fusion transcript formation and inter-individual variability. We conducted a genome-wide fusion transcript analysis in post-mortem human brain tissues from 312 individuals, identifying 1458 distinct fusion transcripts in temporal cortex and cerebellum. We showed that many fusion transcripts have protein coding potential, further supported by ribosome profiling data.

SUBMITTER: Moses C 

PROVIDER: S-EPMC12721320 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature