Month: January 2016

Latest from the 100,000 Genomes Project

Across England patients with cancer are now being recruited to the main phase of the 100,000 Genomes Project, giving the fight against cancer a significant boost. Minister for Life Sciences George Freeman MP announced the news at the Festival of Genomics in London yesterday.

Speaking at the conference, the Minister also announced that the government has committed a further £250 million in funding for genomics as part of the recent Spending Review.

George Freeman MP and Dame Sally Davies

George Freeman MP and Dame Sally Davies.

Cancer patients are joining those with rare diseases as part of the 100,000 Genomes Project. Patients are being recruited through 13 NHS Genomic Medicine Centres across the country.

With a patient’s consent, DNA from their tumour is sequenced, and then compared to DNA from healthy cells from a sample of blood.

Scientists will be able to build a more detailed understanding of how DNA affects a patients susceptibility to disease and response to treatment. In some cases, DNA sequencing will mean a specific recommend treatment can be recommended, based on a patient’s individual genome changes.  This has the potential to benefit patients here in the UK, and could also help in the global fight against cancer.

Secretary of State for Health, Jeremy Hunt said:

“Genomics is the future of medicine and the sequencing of cancer DNA confirms why the UK is a global leader in this field. Over half a billion pounds has been invested in genomics to ensure that NHS patients continue to benefit from the prospect of better diagnosis and better treatments.”

Life Sciences Minister George Freeman MP added:

“The recruitment of cancer patients is a significant milestone in the revolutionary 100,000 Genomes Project. It will help to unlock our understanding of the causes of this devastating condition, make the UK a leader in genetic research, and provide better diagnosis and more targeted treatment for thousands of NHS patients across the UK.”

Lloyd Sisters, Mary,Sandra and Kerry

Lloyd Sisters Sandra, Kerry and Mary.

Three people joining the project are the Lloyd sisters: Mary, Sandra and Kerry. All three were diagnosed with breast cancer within 15 months of each other.

The sisters heard about the 100,000 Genomes Project, and signed up through University Hospitals of Leicester NHS Trust in order to understand more about their conditions, and how their families might be affected.

Mary said “I was diagnosed in 2013 just after I retired. Then it was Kerry in January 2014, who still has children at school. It was horrendous. Then Sandra in February 2015. You just wonder when it’s all going to end. We’re all keen to take part. Finding out more opens it all up for the rest of our family.”

Sir Harpal Kumar, Cancer Research UK’s chief executive, said:

“It’s very exciting news that the first cancer patients are being recruited to the main phase of this ground-breaking project. The comprehensive mapping of patients’ DNA will reveal a vast amount of information that could help doctors and scientists develop new ways to prevent, diagnose and treat cancer more effectively in the future.

“Precision medicine is already having an impact on some cancer patients, who are benefitting from newly-developed, targeted treatments such as the skin cancer drug Vemurafenib. We hope that, one day, treatments based on the specific characteristics of the tumour, including the genetic make-up, can be offered to all patients – and this latest phase of the 100,000 Genomes Project is another important step towards this.”

The project has already delivered its first successes, with children at Great Ormond Street Hospital recently receiving life-changing diagnoses.

Sir John Chisholm, Executive Chairman of Genomics England said:

“The data from all  our participants provides a powerful resource for researchers  and  we hope that new understanding, diagnoses and treatments for rare diseases and cancer can be developed as a result of this.  Working together with the NIHR BioResource, Cambridge University, Cancer Research UK and Illumina has enabled Genomics England to reach this important milestone.”

Prof Sue Hill, Chief Scientific Officer for NHS England said:

“By giving clinicians and researchers access to their DNA and health history, genomic ‘patient’ pioneers such as the Lloyd sisters are helping to put the 100,000 Genomes Project and the NHS at the forefront of science. Our clinical staff are driving through new tumour tissue handling, preparation and assessment methodology across the NHS Genomic Medicine Centres which will lead to higher quality samples and faster, more accurate results for patients. The global community is now looking to Genomics England and its NHS partners to set global standards for tumour DNA extraction, whole genome sequencing and its analysis.”

Chief Medical Officer, Dame Sally Davies, also announced that her annual report for 2016 will focus on genomics, addressing some of the emerging issues in the field.


Here’s a video featuring Sir John Chisholm, George Freeman MP, Dame Professor Sally Davies, and Illumina’s Peter Fromen speaking on how the 100,000 Genomes Project is leading the way in transforming healthcare for NHS patients.

PanelApp has a new look

GenomicsEngland 150915.00_05_02_15.Still052The Genomics England PanelApp, a crowdsourcing tool that allows knowledge of rare disease genes to be shared and evaluated, has a new look for the New Year.
Over the past few months, we have worked to incorporate feedback from users and added new features which will make it easier to review gene panels.

Below are some screenshots of the new look. You can explore the platform here (opens in new window).

New features

You can now filter through the list gene panels – of which there are currently 170 across a whole spectrum of rare diseases – to help narrow your search and find ones you want to review or download. This list panels can also be sorted based on how many genes have been evaluated or how many expert reviewers have assessed each panel.

The sort and filter feature also works when you’re viewing a particular panel. Let’s say you want to look at the ‘Early onset and familial Parkinson’s Disease’ (opens in new window) panel, you can choose to show only genes that are on the ‘green’ list (meaning that they are very likely be the cause of the disease). Alternatively the genes can be sorted and filtered by name, number of reviews or the mode of inheritance.

Why is PanelApp important?

The aim of PanelApp is to utilise expertise and knowledge to establish a final diagnostic grade gene panel for each disorder. These will be used in the classification of genetic variants to aid clinical interpretation of rare disease genomes, and help to deliver life-changing results for patients and their families taking part in the 100,000 Genomes Project.

Thank you to all those who have already reviewed panels, your contribution is greatly appreciated and within each gene panel you can see acknowledgement of every expert reviewer. We have started to evaluate the reviews we have so far, and will revise and update the gene panels (Version 1.0) for use in the analysis of genomes in the 100,000 Genomes Project.

There are still many gene panels that require expert review. We are asking all rare disease experts to contribute. You can register to become a PanelApp reviewer here.

panelapp before and after

Championing recruitment to the 100,000 Genomes Project

Mehul Dattani - NTGMCThe Endocrinology Service at Great Ormond Street Hospital (GOSH) and University College London Hospitals (UCLH) is an extremely busy service that is predominantly outpatient based. The service provides care to a large number of patients with rare congenital disorders; the aetiology (causation) of the majority of these disorders is unknown. The major disorders that we look after are disorders of growth including complex forms of hypopituitarism, disorders of adrenal function, disorders of sex development, disorders of thyroid function, disorders of reproductive function, disorders of the pancreas and insulin secretion, and disorders of calcium homeostasis.

Investigators within the department are highly research active and have successfully identified a number of genetic causes underlying these disorders. However, overall, to date, only 10-25% of disorders have been explained in terms of aetiology.

Parents of our patients are extremely keen to understand their child’s condition, and in particular, what caused it. They often live in fear and with guilt that they may in some way have contributed to the causation of the condition. They also have a significant anxiety with respect to recurrence of the condition in future pregnancies, and even in future generations. So, the identification of an aetiological basis to the condition might allay their fears and mitigate their anxiety.

Importantly, we hope that the identification of a molecular pathogenesis to the condition using the 100,000 Genomes Project will allow an improved understanding of the conditions, the likely prognosis in terms of lifespan, associated morbidities and disease progression, and perhaps of greatest relevance to the patients and their families, novel therapies for these often highly devastating conditions.

This is why we have encouraged recruitment to the project and hope to continue to do so, helped by the families who are under our care and who want not only the best healthcare for their children, but also help future patients with similar disorders.

Professor Mehul Dattani is currently Head of Paediatric Endocrinology at GOSH, UCLH and UCL Institute of Child Health (ICH). He has an active clinical practice encompassing all areas of paediatric and adolescent endocrinology at GOSH and UCLH.

First children receive diagnoses through 100,000 Genomes Project

The first children to receive a genetic diagnosis through the 100,000 Genomes Project have been given their results at Great Ormond Street Hospital (GOSH), part of the North Thames NHS Genomic Medicine Centre.

Both Georgia Walburn-Green and Jessica Wright had rare, undiagnosed, genetic conditions when they joined the Project. Whole genome sequencing pinpointed the underlying genetic changes responsible for their conditions.

As well as removing a large amount of uncertainty for the families, the results stand to have a major impact on many areas of their lives including future treatment options, social support and family planning. They also have the potential to help many more children with undiagnosed conditions who may be tested for these genetic mutations early on and be offered a diagnosis to help manage their condition most effectively.

Georgia and her family.

Georgia’s story

Between ages of one and two, Georgia’s family discovered all the problems she had one by one. As well as both physical and mental developmental delay, they found that she had a rare eye condition that affects her sight, her kidneys don’t function properly, and she has verbal dyspraxia meaning they don’t know if she will ever talk. Standard genetic testing brought up nothing and so doctors explained that she had an undiagnosed genetic condition.

Amanda, Georgia’s Mum, said: “I had no idea that it was possible to have an undiagnosed condition. I thought you get told you might have a genetic condition, you have the genetic test, and then you get the answer. Being told that Georgia had an undiagnosed condition was one of the hardest points of our lives as we felt like we were alone.”

When the family heard about 100,000 Genomes Project they were keen to sign up.

This is a pioneering project that will transform the application of genomics in our healthcare system.

Amanda said “As soon as we were on the project I felt a huge sense of relief. I felt that they now had all the information needed to look at the full picture and it just required someone to decipher and understand it. There’s nothing else we could do or give and there would be no other secrets to unlock with Georgia. They had her genome and so the answers had to be there somewhere.”

It was almost exactly a year until they received a phone call from Great Ormond Street Hospital geneticist Maria Bitner-Glindzicz explaining that they had found a mutation in a single gene in Georgia which was likely to be the cause of her problems. This, for the first time, gives Georgia a molecular diagnosis for her condition.

Professor Mark Caulfield, Chief Scientist at Genomics England said “It is our aim to bring new diagnoses and, if possible, identify potential therapies for participants in the 100,000 Genomes Project. This is a pioneering project that will transform the application of genomics in our healthcare system.”

Secretary of State for Health, Jeremy Hunt said: “Ground-breaking outcomes like this one for Georgia and her family are incredibly promising, and are the reason that this Government has invested over £200 million in bringing such revolutionary science to the NHS.

“By sequencing DNA on an unprecedented scale, we are also cementing the UK’s position as a world-leader in 21st century medicine”.

Georgia’s family are now hoping that over time they will find out more about her condition and her prognosis.  They also hope to connect with the other families that have children with the same gene change.

Amanda said: “It’s going to take time to find out more about this gene and what it controls and affects but I’m sure they’ll find more out. Medicine is not yet at the stage to offer genetic therapy but we have come so far in Georgia’s lifetime already that who knows what the future holds.”

Jessica and her family

Jessica’s story

Jessica Wright was also recently diagnosed through the 100,000 Genomes Project.

Mum, Kate Palmer talked about what the diagnosis means for them: “Now that we have this diagnosis there are things that we can do differently almost straight away. Her condition is one that has a high chance of improvement on a special diet, which means that her medication dose is likely to decrease and her epilepsy may be more easily controlled. Hopefully she might have better balance so she can be more stable and walk more. She’s now four years old still looks like a wobbly toddler trying to move around!

A diagnosis also means that we can link up with other families who are in the same boat and can offer support. The condition is still quite rare but there are definitely other children out there who have it. I’m really looking forward to saying ‘We are one of you, we have this problem too!’

More than anything the outcome of the project has taken the uncertainty out of life for us and the worry of not knowing what was wrong. It has allowed us to feel like we can take control of things and make positive changes for Jessica.

It may also open doors to other research projects that we can to go on. These could be more specific to her condition and we are hopeful that they could one day find a cure.”

GOSH Consultant in Clinical Genetics, Professor Maria Bitner-Glindzicz says: “With undiagnosed genetic conditions it really is a case of the more families we test, the more we can diagnose. In order to confidently say that a particular gene is likely to be the cause of a condition and not just natural variation that we see in everyone’s genes, we have to match up gene mutations and symptoms across several children to find common features. The more children we therefore have to cross check against, the more likely it is that we can find these common features and give a diagnosis.”

Watch Jessica’s story in this video: