Enhancing interpretation and reducing inequity in genomic medicine through diverse datasets

Summary

This project aims to advance medical and scientific understanding of the causes and spectrum of rare diseases present in families from underrepresented communities, through analysis of large clinical and genetic datasets derived from diverse populations.

How are we doing it?

Genomic sequencing data generated by the Rare Disease group in Exeter, as well as by collaborators working with underrepresented populations across the world, will be aggregated into a database alongside matched clinical data. This resource will aid in the analysis of genomic data derived from these populations and enable novel approaches to identify genetic diagnoses for the families involved. This initiative will enable many benefits including:

• (a) reinterpretation of genetic variants in clinical databases (e.g. ClinVar and HGMDpro) that currently lack sufficient evidence for accurate classification
• (b) enhanced interpretation of genomic variation, in both previously described disease genes as well as candidate novel disease-gene associations, from individuals affected by rare diseases enrolled during the project, and
• (c) empowered reanalysis of genomic data from individuals affected by rare diseases, for whom previous genetic testing did not identify a diagnosis.

What happens next?

This project will provide a resource to empower the analysis of genomic variation in underrepresented communities included in the study, as well as providing diagnoses to families, and delineating the molecular aetiology of novel monogenic disorders. These outcomes will be directly translated into improved diagnosis, management and treatment of rare diseases in diverse populations.

Funding

NIHR Exeter BRC

People Involved

Professor Emma Baple and Professor Andrew Crosby