1. The 100,000 Genomes Project Dr Richard Scott
Clinical Lead for Rare Disease, Genomics England
Consultant Geneticist, Great Ormond Street
14th October 2017

2. Outline The 100,000 Genomes Project Our Rare Diseases programme
For participants (with metabolic disorders)
For researchers
After the 100,000 Genomes Project
13 November 2018

3. The 100,000 Genomes Project Background
Announced by the former Prime Minister in December 2012
An Olympic Legacy
Genomics England announced by Secretary of State for Health in speech during NHS 65th Anniversary Celebrations, July 2013
The project – launched by David Cameron in Genomics England set up to deliver it – a company but wholly owned by DH.
13 November 2018

4. The 100,000 Genomes Project in numbers
One genome is about 200GB – it would take up the memory of an average laptop
The project will generate about 21 petabytes of data – that’s 2,000 years worth of music on an mp3 player!
13 November 2018

5. Four main aims 1. To bring benefit to NHS patients
2. To create an ethical and transparent programme based on consent
3. To enable new scientific discovery and medical insights
4. To kickstart the development of a UK genomics industry
13 November 2018

6. How it works
Diagram showing high-level process from a patient consenting > samples collected > biorepository > sequencing > analysis
The position of known genes is marked on the reference sequence.
Every person has millions of differences (variants) to the reference sequence
Most of these differences are harmless – they are the reason we are all unique. But some could be causing a disease.
Bioinformaticians use a variety of tools and techniques to filter these differences down from millions to just a handful that could be harmful.
If a change is thought to be the cause of someone's symptoms – this is fed back to the NHS.
The lab then confirms the result.
The diagnosis and its implications are is discussed with the patient.

7. A co-ordinated response across health and care
Co-ordinating genomic knowledge to make the UK a world leader
Sequencing 100,000 genomes to advance genomic knowledge
Turning genomic knowledge into health interventions
Ensuring the NHS Workforce is skilled and able to deliver for patient benefit
Using genomic knowledge for prevention and health protection
Key delivery partners – NHS England, HEE, DH and PHE
13 November 2018

8. The infrastructure for delivery
Nationwide network of 13 NHS Genomic Medicine Centres – each serving ~3-5 million population
Each NHS GMC lead ‘contractual’ organisation works with local hospitals as delivery partners (over 70 hospitals across England)
Integrated with existing regional genetic laboratories and clinical genetic services and local pathology laboratories
Mapped to Academic Health Science Networks (AHSNs)
The infrastructure for delivery
GEP HEI x9
There are 13 Genomic Medicine Centres (GMCs) which are located in the major hospitals in England who are identifying, consenting and obtaining samples from suitable patients. These GMCs have local delivery partners which are the smaller local hospitals meaning that there should be access to the program England. Once the samples have been extracted and the data is available for the participants, the samples are sent to a biorepository which plates all the samples for sequencing and stores the remaining sample. The sequencing occurs in a purpose built centre in Hinxton Cambridge which is a high throughput facility which Illumina run using HiSeq X platforms.
The sequence data is placed into the Genomics England data centre along with the clinical data from the participant.
Clinical reports are generated which goes back to the GMC. In addition we have clinical interpretation partners – GECIPs, which are the clinical and research communities that have access to de-identified data for research and to help with interpretation of challenging cases. There is also a gene consortium made up of pharma companies who can access the de-identified data to drive R&D and clinical trials.
13 November 2018

9. Why are we doing rare disease?
Collectively they are very common and affect a significant number of the UK population
Mainly affect children, only 50% are provided with a genomic diagnosis
In the Project – we are looking at about 200 rare diseases.
13 November 2018

10. Rare disease programme
Disorders nominated by the NHS and academia
Over 200 disorders so far
Eligibility criteria: describe which patients to recruit
Data model: describes the clinical information to be collected for each disorder
Data /sources we’re collecting in the rare disease programme
Gene panel: the genes to be analysed first for patients with that disorder

11. Undiagnosed metabolic disorders eligibility
Any patient seen in a metabolic clinic considered likely to have a monogenic disorder by a consultant Metabolic physician
Except where the genetic cause is already known
13 November 2018

12. What are we telling participants?
Information about a patient’s main condition
Information about additional ‘serious and actionable’ conditions (optional)
Carrier status for non affected parents of children with rare disease (optional)
Image courtesy of Health Education England
13 November 2018

13. What does recruitment involve?
Consultant suggests recruitment
Appointment to
go through consent process
take blood samples
Usually the preference is to recruit the affected individual(s) plus their parents
other family structures are fine!
Recruiting consultant’s team will contact you again when results are available
13 November 2018

14. First children receive diagnoses (GOSH)
Georgia Walburn-Green, aged 4
Jessica Wright, aged 4
Both children were part of the pilot study at Great Ormond Street Hospital (North Thames GMC)
Jessica (aged 4) has a rare condition which causes epilepsy and affects her movement and general development.
WGS revealed she has a rare genetic variant which causes Glut 1 deficiency syndrome.
She can now be put on a special high-fat diet to reduce the number of seizures.
Georgia Walburn-Green has physical and mental developmental delay, a rare eye condition that affects her sight, and verbal dyspraxia
Given a molecular diagnosis from WGS

15. Genomics England Clinical Interpretation Partnership
2,500 prospective GeCIP domain members
300 institutions, 24 countries
Institution
Count
UK Academic
1744
NHS Trust
634
International Academic
198
Other
333

16. Genomics England Clinical Interpretation Partnership in numbers
researchers
2600+
academic institutions world-wide
341
researchers have been verified by 54 institutions with
a signed Participant Agreement
1056
From Kate W
683
researchers have been verified and have ARC approval
13 November 2018

17. Industry Consortium and Partners
13 pharma/diagnostics/SMEs
Precompetitive consortia
Work together on 5,000 WGS to shape data centre
Individual company interactions
Inward investment from Illumina
£50m in new HQ in Cambridge
AbbVie
Alexion Pharmaceuticals
AstraZeneca
Biogen
Dimension Therapeutics
GSK
Helomics
Roche
Takeda
Berg
Boehringer Ingelheim
UCB
Intellia

18. Patient engagement – our National Participant Panel
Includes current participants, quarterly meetings
Members sit on key committees including the Data Access Review Committee, GeCIP Board, Ethics Advisory Committee
Produce and input in materials e.g. flyers, leaflets, animations
How we work with participants
13 November 2018

19. Health Education England
Genomics Education Programme
11 University providers of MSc in Genomic Medicine
Aimed at NHS healthcare professionals working in England
Full/part time study
Fully funded places available through HEE
Individual (CPPD) modules available for range of professional backgrounds and groups (e.g. medicine, nursing, healthcare scientists and technologists).
Online training courses and resources
The fundamentals of genomics
Bioinformatics
The consent process
Training the workforce – resources available, online courses and a new MSc course
13 November 2018

20. Latest figures
As of July 2017, we have now sequenced over 30,000 whole genomes from patients and their families. 
A semi-automated reporting pipeline has been built, and results are now being returned to the NHS.
Reports on the first ~2,000 rare disease families (4,200 participants) have been returned to recruiting hospitals
Expecting a further ~4,500 families (~9,000 participants) in next 4 months

21. After the 100,000 Genomes Project
NHS England are reorganising the genetic laboratories
Whole genome sequencing will become an NHS test in some settings
NHS England will also introduce measures to make availability of testing more equitable across the country
Inborn errors or metabolism are expected to be well served by the changes
13 November 2018

22. Building the future of genomic medicine
100,000 WGS on NHS patients and pathogens
Concentrating the UK Genomics Knowledgebase in one location
The NHS, academics and industry partnerships at the outset to drive Genomic Medicine into the NHS and create wealth
Building the human capacity and capability
Key international partnerships to add value
Leave a legacy of NGS Centres, sample pipeline and biorepository, large-scale data store that makes this usable by the NHS
New diagnostics and therapies and opportunities for patients

23. Stay in touch @genomicsengland #genomes100k
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