Alternative splicing in health and disease

Using long-read DNA sequencing we can reveal the many, long-undiscovered forms that a single gene can take - leading us to new therapeutic targets.

Project Summary.

Led by: Wilfried Haerty

Past Funders: 

UKRI Medical Research Council (MRC)

Current Funding: 

MDC Psychiatric Consortium

UKRI Biotechnology and Biological Sciences Research Council (BBSRC)

Around 95% of human genes undergo alternative splicing, the process by which multiple transcripts with different sequences are produced from a single gene.

Alternative splicing is a highly regulated process, and its disruption is associated with many disorders and diseases. Many primary candidate genes are broadly expressed which may have an impact on drug efficacy and toxicity.

Understanding how AS and its associated mechanisms - such as differential isoform expression or exon usage - work to parse genomic blueprints into the staggering diversity of known biological structures is one of the key themes underpinning our research. 

Impact statement.

Alternative splicing (AS) is the process of generating multiple transcripts from a single gene through differential exon usage.

Nearly 95% of our genes undergo alternative splicing. AS is a highly-regulated process with significant evidence of a developmental stage, tissue, or cell-specific regulation. Dysregulation of the splicing machinery or of transcript splicing is directly associated with many disorders and diseases.

In close collaboration with industrial partners and collaborators at the University of Oxford, we are developing experimental and computational approaches to characterise splicing diversity, investigating splicing regulation, and identifying transcripts arising from candidate genes expressed specifically in a tissue of interest. Those transcripts will be primary candidates for further target development.