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expert reaction to study looking at the 100,000 Genomes Project pilot on rare diseases

A study published in the New England Journal of Medicine (NEJM) looks at the 100,000 Genomes Pilot on rare-disease diagnosis in health care.

This Roundup accompanied an SMC Briefing.


Prof Felicity Boardman, Professor in medicine ethics and society, University of Warwick:

“This is an important piece of work that demonstrates the role of whole genome sequencing in achieving diagnosis for families living with rare conditions. My own research highlights just how significant diagnosis is for families living with rare conditions, not only in terms of treatment, but also social support and identity. One of the key challenges facing the use of whole genome sequencing within the NHS in the future will be its translation into screening contexts (e.g. of otherwise healthy newborns), which may facilitate the pre-symptomatic identification of rare conditions, but is also associated with a range of social and ethical consequences.”


Dr Bridget Bax, Reader in Rare Diseases, St George’s, University of London, said:

“The key to the successful diagnosis of the patients reported in this study is the design of the analysis, where the investigators integrated the clinical features of the disease with genome sequencing data. This study emphasises the importance of collecting health information over time (natural history data) from patients with rare diseases.  In the future, it is expected that the integration of difference types of data, along with the application of technological advances, will underpin diagnosis breakthroughs and the development of new therapies.”


Prof Chris Inglehearn, Professor of Molecular Ophthalmology, University of Leeds, said:

“This study highlights and, for the first time, quantifies the added value of sequencing the whole genome in patients with inherited diseases, rather than just the small percentage of human DNA that codes for genes, as is the most common practice at this time. The results obtained show beyond doubt that human genome sequencing can revolutionise medical care for a wide range of human diseases.

“However, the UK 100,000 Genomes Project, the source of the data used in this study, can prove difficult for clinicians and researchers to access, and our own recent work on this resource revealed anomalies in the clinical information available for some patients. Unless addressed, these problems risk limiting the extent to which this remarkable dataset and technology can be exploited to for patient benefit.”


Prof Darren Griffin, Professor of Genetics, University of Kent, said:

This study is undoubtedly good news for healthcare and for the NHS. The ability to diagnose rare diseases early is the key to successful treatment and, as whole sequencing technology gets cheaper and cheaper, its widespread roll out is becoming inevitable. One of the great challenges however will be those DNA variants that have unknown, or unsure clinical significance. More studies such as these, will help to clarify this matter in time. 



Prof Ros Eeles, Professor of Oncogenetics, The Institute of Cancer Research, London & Honorary Consultant in Clinical Oncology and Oncogenetics, The Royal Marsden NHS Foundation Trust, said:

“This is a very exciting paper that shows the potential of using genetics in healthcare. It is a study of rare diseases, where often the diagnosis is uncertain and many investigations tend to be necessary. This important paper has shown that genetics can be used to make the diagnosis, and indeed speed up the diagnosis, in about 25 per cent of the cases.

“It is very important to note that these were families with rare conditions and therefore this is not representative of the unaffected population. The potential of genetics will eventually need to be integrated into healthcare and that potentially would lie in general practice. At The Institute of Cancer Research, London, in collaboration with the 90 Sloane Street Genetic centre ( and The Royal Marsden NHS Foundation Trust, together with colleagues at the Royal Brompton Hospital, we are already taking this further – we are undertaking a pioneering study to assess how whole genome screening could be used in the future as part of a medical screen in primary care in adults.”



‘100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report’ by the 100,000 Genomes Project Pilot Investigators was published at 22:00 UK time on Wednesday 10th November.

DOI: 10.1056/NEJMoa2035790



All our previous output on this subject can be seen at this weblink:



Declared interests

Dr Bridget Bax: “I declare no conflict of interest.”

Prof Darren Griffin: “No conflicts of interest.”

None others received.

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