Every month, one member of the TGMI team tells us why they are so committed to the vision of the TGMI, and shares a bit more about their work and interests. This week we hear from Matthew Hurles, Head of Human Genetics and Senior Group Leader at the Wellcome Trust Sanger Institute.
What has been the main focus of your work to date?
I jointly lead the Deciphering Developmental Disorders (DDD) study, working with over 13,000 families across the UK and Ireland, with children with severe, undiagnosed developmental disorders. We are applying the latest genomic technologies to diagnose these children, and can currently diagnose about 35%. Optimising data analysis and clinical curation of existing knowledge have been critical components of being able to apply these genomic technologies at scale. I also co-lead the DECIPHER initiative that enables patients and their families to share their genetic and clinical data widely, irrespective of where they are in the world. This data sharing has led to well over 1,000 research publications and many diagnoses for previously undiagnosed patients.
What are you most excited about in genetic medicine?
– The prospect of cost effective genetic diagnosis for all that need it.
– Helping patients to benefit from sharing their genetic and clinical data openly.
– The potential of using anonymised, routine clinical data to transform our understanding of clinical applications of genetics.
What are you most concerned about in genetic medicine?I’m concerned about four things:
-Families are being deprived of necessary support despite having children with real needs because of the lack of a genetic diagnosis. The need to receive support should be uncoupled from the current ability of clinical practice to find a genetic cause underlying the patients’ needs.
-I’m also concerned about paternalism with regard to enabling patients and their families to share their data, either for their own benefit or for altruistic reasons.
-There is a lack of a sustainable model for maintaining the knowledge resources that are critical to support genomic medicine. These resources should not be dependent on the research funding community, but should be funded by healthcare.
-The lack of recognition that the rapid improvement in our knowledge of what genes can cause genetic diseases means that regular re-interpretation of genetic data in undiagnosed patients should be a cornerstone of good clinical practice.
Why did you get involved in TGMI?
It was a natural follow-on from our work on the DDD project, an opportunity to learn from other translational projects in different clinical areas, to define a set of resources of general utility.
What is the most important thing that you would like the TGMI to achieve?
Devising a sustainable, up-to-date, solution to the problem of identifying which genes have been robustly demonstrated to cause rare genetic diseases, and which diseases they cause.
If you had a magic wand (i.e. unlimited people/resources) what would you do to make genetic medicine work?
I would devise a system that enables all clinicians that encounter genetic diseases to identify which patients might benefit from a genetic test, to order a diagnostic genetic test, and to receive results that can lead to appropriate clinical actions, without requiring the clinician to retrain to become entirely genetically literate themselves.
Do you have a favourite gene? If so – what and why?
NR2F2. This is a gene involved in many developmental processes. We previously showed that mutations in this gene can cause congenital heart defects. The DNA sequence around this gene is extremely highly conserved between different species. If we understood the nature of the selection pressures underpinning this conservation we would have gone a long way to understanding the complexities of gene regulation in development, and the role of variation in such sequences in genetic diseases.
What is a surprising fact that few people know about you?
I sometimes make garden sculptures of deer out of copper piping.
If you had a chance to experience a completely different career for a week, what job would you try?
Either a gardener, a mid-wife, a professional cyclist or a child psychiatrist – all for very different reasons.