The 100,000 Genomes Project and Rare Disease Day

No-one has ever attempted whole genome sequencing on this scale before. Much of our work until now has been in establishing the tools and infrastructure we need to deliver results to 100s of participants a week.

Rare disease is a deceptive term. There are 6,000 to 8,000 different rare diseases. This means that although each one is rare, as a group they are common. So much so, that 1 person in 17 is affected with a rare disease. That is 7%.

Until recently, these usually complex and long term diseases have been the second class citizens of the medical world. But now there is an increasing focus on them. It has been a long time coming. For years, people suffering with rare diseases have struggled to be diagnosed, let alone have access to the same expert medical advice and tailored treatment plans that have become the norm for many common long term disorders such as diabetes and heart disease.

The change has come thanks in large part to 'patient power' - witness today's celebration of Rare Disease Day, the brainchild of the Rare Disease patient advocacy group EURODIS, to raise awareness of rare disease. Since its launch in 2008 it has spread to more than 80 countries.

In parallel, strategic responses to the unmet needs of rare diseases have been forthcoming. In the UK, publication of a National Strategy for Rare Disease in November 2013 has been part of the response. Today, an update from the UK Rare Disease Forum has been published, showing progress so far and what work is still to be done. The government also funded our ground-breaking 100,000 Genomes Project, which aims to transform healthcare for people with rare disease and cancer.

About 80% of rare diseases have a genetic cause. The cause is often a single changed 'letter' amongst the 3.2 billion letters of DNA that make up the human genome. Finding that one crucial change is often like finding a needle in a haystack. This first crucial step - identifying the cause of the disease - has remained challenging until now for most rare diseases. In turn, this has prevented medicine from answering the obvious next questions for rare disease patients: what should I expect in the future? Why has the disease happened? Is there a way of curing my disease or any hope of doing so in the future? Will my child have the disease?

The 100,000 Genomes Project is an opportunity to break the mould for patients in the NHS. We will sequence DNA from patients with rare disease and their relatives. By comparing their sequences with people without the disease and by tracking the inheritance of DNA changes through families, we can find the cause in people who medicine has failed to diagnose until now.

No-one has ever attempted whole genome sequencing on this scale before. Much of our work until now has been in establishing the tools and infrastructure we need to deliver results to 100s of participants a week.

Thirteen 'NHS Genomic Medicine Centres' have been commissioned to act as recruitment hubs, each with a network of local recruiting hospitals. Here, participants are identified and consented by local clinical teams and DNA samples and standardised medical data collected. The sequencing itself is performed in a purpose-built facility near Cambridge before the genome sequences are analysed alongside the medical data in a secure, monitored data centre.

The scale of the task is only possible because of the great power of the new sequencing technologies and computing. As Spiderman tells us 'with great power comes great responsibility' and it is with this sense of responsibility that we approach the work: both driving us to capture every ounce of available expertise and to exert the necessary caution when patient's lives are influenced by the outcome of our analysis.

The Project bioinformatics team have established the core analysis 'pipeline', which is further enhanced by the input of genome annotation partner companies. This analysis infrastructure is supplemented by the expertise drawn from a collaboration of more than 2,000 academic researchers from across the UK and the world who form the 'Genomics England Clinical Interpretation Partnership' (GeCIP for short) and from the clinicians at the recruiting hospitals as they receive the sequence results and return them to the participants.

But the aims of the project do not end at interpretation of genome data for diagnosis. The GeCIP research community seeks also to understand the processes that lead to the diseases and to develop precision medicine approaches to their treatment. To enhance the speed with which potential treatment benefits can reach patients, we have established a unique partnership between our academic and NHS partners and companies from pharma, biotech and diagnostics. Through this collaboration, we are developing approaches that will reduce the length of time from the first identification of a cause of a condition to the development of life changing treatments.

We are already making our first diagnoses for families enrolled in the study. We hope that this will become commonplace and that the benefits won't stop there, instead it will become the expectation of rare disease patients to receive the same standard of care and access to precision medicines as for common diseases.


What's Hot