Revisiting genetic determinism: evidence from large population cohorts

Developments in whole genome sequencing technologies have catalysed incredible progress in the diagnosis of rare disease and the discovery of novel disease-associated genes. However, large-scale sequencing of population cohorts has revealed that many healthy individuals carry the same disease-causing variants as patients. The extent of this incomplete penetrance in individuals not ascertained on the basis of a family history or clinical diagnosis is neither well understood nor widely appreciated. In this talk, I will outline recent research into penetrance of different diseases across different populations, and discuss the broader implications of these findings for genomic screening.

Caroline Wright is a Professor of Genomic Medicine in the Department of Clinical and Biomedical Sciences at the University of Exeter UK and Academic Director of the NHS Rare and Inherited Disease Genomic Network of Excellence. Her main research interests are in the clinical application of genome-wide assays for the diagnosis of rare diseases, and she has expertise in analysing exome/genome sequence data particularly in rare paediatric disorders. She has funding from the Wellcome and MRC to find novel genetic causes of disease, improve the interpretation of rare genetic variants, understand the penetrance of rare pathogenic variants, and explore the policy and ethical issues associated with implementation of genome-wide sequencing in healthcare. She is part of the management committee for the UK Deciphering Developmental Disorders Study, and was formerly the project manager for this study at the Wellcome Sanger Institute. She was seconded part-time to Genomics England for a year as Scientific Lead for Validation and Feedback, to help set up the variant filtering system for the rare disease arm of the 100,000 genomes project. She was previously Head of Science at the Public Health Genomics Foundation, and trained in Natural Sciences at the University of Cambridge.