NCM 2022: Characterisation of mRNA isoform diversity in a transgenic model of tau pathology using targeted long-read sequencing
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This study uses Oxford Nanopore Technologies nanopore sequencing to assess splicing variation and isoform diversity in a transgenic mouse model of Alzheimer’s Disease (AD) pathology. We focused on twenty genes robustly associated with AD from genetic studies, using selective gene enrichment to identify novel transcripts in entorhinal cortex tissue from the Tg4510 model of progressive tau pathology and wild-type controls. We detected many novel isoforms, revealing complex usage of alternative start sites and splicing events, not previously annotated in existing genomic datasets. These results further support a role for splicing dysregulation in development of AD pathology. Further work will be undertaken to characterize other AD-associated genes, and to extend these analyses to human post-mortem brain samples.
