Long-read transcriptome sequencing reveals isoform diversity across human neurodevelopment and aging

Abstract

Alternative splicing dramatically increases transcriptomic and proteomic diversity from the coding genome. Long-read sequencing approaches can be used to generate full-length transcript sequences and characterise isoform diversity. We used Oxford Nanopore transcriptome sequencing to profile transcript diversity across human brain development and aging. We identify changes in alternative splicing, with differential transcript usage between human foetal and adult cortex. We show that genes associated with neurodevelopmental and neurodegenerative disorders are characterised by considerable RNA isoform diversity. Our data confirm the importance of alternative splicing in the human cortex and represent an important mechanism underpinning gene regulation in the brain.

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