Lead: Professor Jenny Taylor
Oxford researchers played a major role in the development of the 100,000 Genomes Project, by pioneering the clinical translation of whole genome sequencing (WGS) for rare disease and cancer.
Currently, many patients with rare diseases are left without a timely and accurate diagnosis even after WGS. We are continuing our work looking for rare variants and novel disease genes – including using Oxford’s expertise in machine learning – and then conducting functional assays to understand what they do, with the eventual aim of devising treatments for patients with rare diseases.
A key partner in this work is the Oxford-Harrington Rare Disease Centre (OHC), whose mission is to deliver cures for rare diseases.
We are aiming to develop new laboratory methods and bioinformatic pipelines using machine learning to identify which variants cause disease and so increase the number of rare disease patients getting a diagnosis.
This will include in areas such as craniosynostosis, where the bones in a baby’s skull fuse too early; ciliopathies, a range of disorders associated with abnormal function of cilia in the cells; endocrine disorders, which affect the system of glands and organs that regulate the release of hormones; and the inherited cardiomyopathies.
This builds on the work already done around hypertrophic cardiomyopathy by Professor Hugh Watkins in uncovering the genetic changes that can cause sudden cardiac death in young people; and major funding he has received to develop a the first cure for these inherited heart muscle diseases.
We are conducting pilot studies to assess the feasibility of genetic screening programmes in newborns for devastating conditions such as spinal muscular atrophy (SMA) and congenital myasthenias. These will inform a planned Genomics England/NHS national newborn-screening programme. Our SMA screening pilot study, the first such in the UK, is already under way.
We are working with colleagues in the BRC’s Gene and Cell Therapy Theme to develop a new clinical gene editing pipeline that will accelerate the implementation of gene therapy clinical trials in a range of conditions, including immune deficiencies, lung and eye diseases
We are also looking to work with industry partners, such as through the Open Targets partnership, to identify and test new genetics-led drug targets that can allow neglected rare diseases to be treated. We are building on the Priority Index, a resource for genetic targets in immune-mediated disease, and working to validate our targets with the Centre for Medicines Discovery and Oxford’s experimental medicine Clinical Research Facility.