Genetic testing for some inherited diseases using ultra-fast next generation DNA sequencers could be piloted by some NHS clinical laboratories within two years. The new techniques would allow - for the first time - NHS laboratories to screen hundreds of genes simultaneously. This is essential when the same symptoms and signs may be caused by mutations in one of many different genes.
Next-generation genetic sequencing is increasingly used in research. But researchers from Oxford University and Oxford Radcliffe Hospitals NHS Trust are evaluating these sequencing techniques for use in clinical medicine with specific projects on inherited ataxias and retinal degeneration.
Dr Andrea Nemeth, Consultant Clinical Geneticist and Honorary Senior Lecturer at Oxford's Churchill Hospital and the University of Oxford, is part of a team that is currently testing two next-generation sequencing platforms - the Roche 454 and Illumina systems - for use in a hospital setting. They're benchmarking these two next-generation platforms against gold standard Sanger sequencing techniques used in the Medical Genetics Laboratory at the Churchill Hospital.
Dr Nemeth says: 'The requirements for clinical conditions tend to differ from research projects. Accuracy is crucial in the clinical setting because people may make life decisions based on a genetic test. Furthermore, sequencing all genes in the genome - whole exome sequencing - will be invaluable in research projects, but in clinical laboratories we may want to sequence fewer genes but in more patients per run'.
The team are experimenting with three different targeted DNA capture methods, Raindance, Nimblegen arrays, and Agilent SureSelect, which capture genes of interest rather than sequencing all the genes in the genome.
'Each DNA capture and sequencing platform has strengths and weaknesses in different situations, depending on the number of genes to be analysed and how many patients need to be analysed per year. We are trying to work out which platforms are best for different clinical applications', says Dr Nemeth.
'It is essential that all clinicians have an understanding of this new technology as they will be the key people to drive development of the different technologies forward for clinical use', adds Dr Nemeth.
The team initially aims to identify a suite of common genes suitable for diagnosing ataxias and inherited retinal degeneration. However, the sequencing technology can be used to detect mutations in many different genetic disorders and it is hoped that the evaluations performed will assist other clinicians and scientists to develop their own research projects for different diseases. The team also hopes to use whole genome sequencing to identify novel genes associated with ataxias and inherited retinal degeneration and to better understand the role of genetic mutations.
'There are probably lots of patients with ataxia caused by mutations in genes we are unaware of, so we will need to use whole exome capture in addition to the targeted capture we are using at the moment. We hope our research will lead on to many other research projects as well as improving diagnostics', Dr Nemeth said.
The research is funded by AtaxiaUK, the Oxford Biomedical Research Centre, the National Institute of Health Research and DeNDRoN.
Dr Andrea Nemeth, Consultant Clinical Geneticist at Oxford's Churchill Hospital presented her work at 10:00 on 6th September 2010 at the annual BSHG conference held at the University of Warwick from 6th to 8th September 2010.
Other members of the team working on this project are Dr Susan Downes, Dr Kevin Talbot, Dr Zam Cader, Professor Andrew Wilkie, Dr Ioannis Ragoussis, Dr Richard Copley, Dr Morag Shanks, Dr Alex Kwasniewska, Dr Jenny Taylor, Dr Anneke Seller, Dr Emily Packham, Dr Treena Cranston and Dr Penny Clouston.