Are you sequencing 100,000 patients?
No. This is a common misconception but it’s 100,000 human genomes, not patients. Every cancer patient will contribute two genomes for comparison (one from a healthy cell, one from their cancer). Three genomes will come with every rare disease participant for comparison (one from the affected person and two more from close blood relatives where available). Assuming half of the genomes will come from cancer and half from rare disease, the figures work out roughly like this:
Cancer = 50,000 genomes – 25,000 patients
Rare disease = 50,000 genomes – 15,000 patients and 35,000 healthy relatives
So about 75,000 people in total, 40,000 of which will be patients.
Why 100,000 genomes?
The number was chosen based on experience from other studies like the UK10K programme. As the cost of sequencing fell and the knowledge about rare variants increased it was decided that 100,000 genomes would be the right balance between cost and benefit for NHS patients to build a clinical and research legacy.
What’s the timeline?
The 100,000 Genomes Project has been running a series of pilots with Cancer Research UK, the NIHR Biomedical Research Centres and a number of hospitals during 2014 and 2015. We are learning a lot from the pilots which we will be applying to the main phase of the Project which runs from 2015 to 2017. All 100,000 samples will be sequenced by the end of 2017 when the Project ends.
Why cancer, rare disease and infectious diseases?
The government’s Strategy for UK Life Sciences, One Year On report (December 2012), announced the establishment of the 100,000 Genomes Project. In this report, it outlined that the Project would initially focus on cancer, rare diseases and infectious diseases because the introduction of genomic technology in these areas first would most likely bring the greatest benefit for NHS patients.
Prior to Genomics England being established, the Chief Medical Officer for England, Professor Dame Sally Davies, established a Strategic Priorities Working Group for the 100,000 Genomes Project which was chaired by Professor David Lomas, Dean of Medical Sciences at University College London. Based on the advice of that working group, rare diseases, certain cancers, and infectious disease were recommended for inclusion in the Project.
Based on robust scientific advice and clinical evidence, Genomics England and NHS England have now selected the initial rare diseases and cancers for the main programme. The 100,000 Genomes Project Protocol
outlines in detail the basis on which the specific cancers and the rare diseases were selected. As whole genome sequencing is a new technology about to be applied in the NHS for the first time, we want to maximise medical insights alongside new scientific discoveries as early on as possible so we can understand how genomics influences disease and can be applied within a healthcare setting. The expectation is that the range of specific diseases selected at this stage of the Project will bring us these insights and give us a much greater understanding and knowledge which can be applied to other diseases in the future.
How is Genomics England working with Illumina?
One of the challenges of this Project when it was first established was that there were no sequencing machines in England of the type capable of supporting the Project, both in terms of the number of machines required to sequence 100,000 genomes and the accuracy that researchers and clinicians would need.
Genomics England signed a partnership agreement with the sequencing firm Illumina in August 2014
which ensures there is sufficient sequencing capacity. With the generous support of the Wellcome Trust, the sequencing machines will be located in a new £27m sequencing centre at the Wellcome Trust’s Sanger Institute near Cambridge.
What is sequencing?
Reading along DNA to determine the order of every base pair, letter by letter.
What is variant calling and annotation?
After a patient’s sample has been sequenced, the next step is to compare the patient’s genome and a reference genome; a process called variant calling. There can be up to two million differences between individuals. The next hurdle – annotation - is to interpret the meaning and importance of those differences. Some of the differences will be natural variations that are harmless between individuals, but some will be damaging and may cause or increase the susceptibility to disease.
How is Genomics England working with the NHS?
NHS England and the 11 NHS Genomic Medicine Centres
are important delivery partners for Genomics England. We are working in collaboration to ensure not only that this landmark project succeeds, but that when the project concludes in 2017 there is a sufficiently robust genomics infrastructure in place to enable genomic medicine to be carried out routinely in the NHS. Specifically, NHS clinicians and healthcare teams working in NHS Genomic Medicine Centres will identify, enrol and register suitable patients (and members of their family in the case of rare disease patients); be responsible for taking informed consent; capturing clinical information; ensuring there is an adequate supply of samples and feeding back results to participants. Clinicians and the GMCs will be important partners within the Genomics England Clinical Interpretation Partnership (GeCIP)
to help us learn how to interpret genomic data in a clinical context and embed that learning within the NHS.
Is this an England-only programme? What about the rest of the UK?
Genomics England’s funding is intended to support sequencing for patients identified via hospitals selected by NHS England. It is hoped that the devolved nations (Scotland, Wales and Northern Ireland) will join the Project. There is nothing to stop other parts of the UK or indeed countries overseas from approaching Genomics England, for example, to add their sequencing data to the Genomics England database.
How is Health Education England involved in the 100,000 Genomes Project?
Health Education England
is a key delivery partner in the 100,000 Genomes Project. The work of Health Education England’s genomics education programme will address the longer term issues of genomics education and training: building on the legacy of Genomics England, supporting workforce transformation through the development of skills in the NHS that helps better adoption and spread of genomic technologies.
Why is Public Health England leading the infectious disease part of the 100,000 Genomes Project?
One of Public Health England’s top priorities is ‘to protect the public’s health from infectious diseases and other hazards to health’ and provides the specialist microbiology services in England. As a result, Public Health England has been asked to lead this part of the 100,000 Genome Project, focusing on the potential importance of whole genome sequencing in some infectious diseases, such as tuberculosis, in public health responses, as well as implications of clinical care of patients.
What is new about the 100,000 Genomes Project? Is the 100,000 Genomes Project a research project, a clinical project or an NHS transformation project?
The 100,000 Genomes Project is not simply a research project. It is a transformation project using genomic medicine to change how NHS patients are treated. It is also a new way of caring for patients. To sequence 100,000 genomes over four years is immensely ambitious and has never been done on this scale anywhere in the world before.
Genomics England is working within the UK healthcare system. This is to ensure the project will leave a legacy of world class genomic medicine for patients benefit. This means training healthcare staff in new skills and changing our practices to maximise our ability to use this technology. We are also leaving an infrastructure in place to handle DNA samples and clinical data required for whole genome sequencing.
How are you recruiting patients? How can I get involved?
For a rare disease patient and their family members to participate in the Project, the patient will need to have been referred by a clinician working in a NHS Genomic Medicine Centre. This will often be a clinical geneticist. For cancer patients, their referring clinician, usually an oncologist will invite the patient to take part.
What is the purpose of Genomics England and the 100,000 Genomes Project?
Genomics England, with the consent of participants and the support of the public, is creating a lasting legacy for patients, the NHS and the UK economy, through the sequencing of 100,000 genomes by 2017. It has four main aims:
- to bring benefit to patients
- to create an ethical and transparent programme based on consent
- to enable new scientific discovery and medical insights
- to kickstart the development of a UK genomics industry
The project is focusing on patients with a rare disease and their families, as well as patients with certain common cancers (breast, bowel, ovarian, prostate, or lung). We will also be recruiting patients with chronic lymphocytic leukaemia (CLL) in collaboration with existing clinical trials.
How and to whom is Genomics England accountable?
Genomics England is accountable to the Secretary of State for Health who is the sole shareholder of Genomics England. The Secretary of State is accountable to Parliament which examines and challenges the work of the government so Genomics England is ultimately accountable to the UK public.
Why was Genomics England set up as a limited company?
The Department of Health chose to establish Genomics England as a subsidiary limited company as it was the most effective way to ensure the 100,000 Genomes Project got up and running as quickly as possible. If it was established as an agency or a public body then this would have required primary legislation. The implication of choosing this latter option would have had a knock-on effect on patients by delaying any benefit from any new medical advancements found as a result of whole genome sequencing. It also goes against government policy to establish more agencies and public bodies.