Clinical genome sequencing goes national

The results of the WGS500 project have just been published. Here Dr Jenny Taylor, who is Programme Director of the Genomics Medicine Theme of the Oxford Biomedical Research Centre (BRC), explains how WGS500 was a forerunner of the Genomics England initiative.

DNA double helix with dataOxford is one of eleven locations that Genomics England Ltd (GEL) has chosen to host a Genomic Medicine Centre, which will be responsible for recruiting patients for the main phase of the 100,000 genomes project. Up till now GEL has been supporting pilot projects in rare diseases and cancer. Through the WGS500 project, a joint project of WTCHG and the Genomics Medicine Theme of the BRC, Oxford has been closely involved in these pilot programmes.

We gained a lot of experience with this kind of study through WGS500, which was a proof of concept. We tried to cover a whole range of genetic conditions to assess whether genome sequencing was going to be useful in the clinic or not. I think we learned a lot from that programme, in terms of how to do recruitment and analysis or follow up results, some of which will get carried on into Genomics England.

That experience was helpful in writing the successful bid for Oxford University Hospitals NHS Trust to be designated a Genomic Medicine Centre. A lot of the funding and infrastructure for the pilots locally came through the BRC and through individual grants that we hold. For example I hold a Health Innovation Challenge grant from the Department of Health, which has given us funding to set up a clinical sequencing facility and sequence a further 500 patients.

From now on NHS England will take responsibility for recruitment for the programme through these selected genomic medicine centres. They will recruit patients with a wide range of diseases suspected to have a genetic basis, and for which there is as yet no clear diagnosis. That will include cancers, but also neuromuscular disorders, cardiovascular disorders, rheumatological disorders, developmental disorders – there is a whole spectrum, and it’s very important that in these genomic medicine centres we try to capture the full range as much as possible.

For each patient, and in some cases for their unaffected relatives as well, the project will collect a full genome sequence. Often in developmental disorders you may have a new mutation in a child but the parents are unaffected, and you will sequence that trio in an attempt to work out what has caused the problem in the child.

For GEL, the sequencing will be done by a commercial partner, Illumina, and the analysis either by GEL’s own bioinformaticians, other annotation partners or by Genomics England Clinical Interpretation Partnerships (GeCIPs). These are groups of experts throughout the UK who will apply for funding to look at the data. The database will be held behind the NHS firewall, and there will be rules about what researchers can download and how they interact with the data in order to protect patient confidentiality.

As well as providing opportunities for research, the programme will deliver diagnoses for many patients, and that will be critical. There are many NHS patients who have been under investigation for some time, for example in rare diseases, who haven’t had a genetic diagnosis: they may be able to get a diagnosis through genome sequencing. For cancer patients it will be possible to profile the tumour and select a treatment based on its genetic profile. There will be discoveries of novel genes, or genes we did know about but didn’t know they caused these other conditions. A huge benefit is that the programme will build a database of correlations between genetic variation and diseases that will allow us to understand a little bit more about the genetic causes of disease.

I think for the Wellcome Trust Centre the establishment of a local Genomic Medicine Centre will bring huge benefits. Researchers in the Centre often have joint positions as clinicians: they will be able to identify patients that should be recruited into the programme, and get diagnoses for their own patients. And by participating in GeCIPs, they will have tremendous opportunities to ask new questions in their own research.

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