Investigating the impact of genetic variations on rare disease

This cluster will use data from the 100,000 Genomes Project to extract, model, and prioritise genetic changes that affect important protein modifications, based on how they might impact protein function. Using advanced bioinformatics tools and automated processes, we’ll test the effects of hundreds of these changes in living cells. By working together with the European Bioinformatics Institute and the ProtVar resource to share our findings, we’re ensuring that our work supports and empowers the broader research community to interpret these genetic changes, and hopefully enable new diagnoses to be provided to patients with rare diseases.

Understanding how genetic changes (missense variants) affect protein function and helping to diagnose rare diseases

Rare diseases are debilitating and can be life-limiting. The 100,000 Genomes Project delivered by Genomics England and NHS England produced a rich catalogue of genomic variation, helping to provide diagnoses for people affected with rare disorders. Many of the genetic changes we find are located in the parts of genes that code for proteins. These changes can alter the instructions for making a protein, causing one building block (amino acid) in the protein to be replaced by another. However, without detailed information about how these specific changes affect the body, most of them can’t currently help doctors make accurate diagnoses.

We aim to understand how these genetic changes (missense variants) affect protein function, helping to diagnose rare diseases. We’ll study changes that affect important protein modifications using a highly cross-disciplinary approach and drawing together the disciplines of computational genomics, biomedical  informatics, mathematics, digital chemistry, bioinformatics, process automation, functional  proteomics, biochemistry, and cell biology.