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Research at the UCL Institute of Ophthalmology over the last 20 years has resulted in the identification of a large number of novel genes that cause inherited retinal disease. These genes have been incorporated into diagnostic tests, which have allowed molecular diagnosis, improved genetic counselling including pre-natal/pre-implantation diagnosis, better information about prognosis and have informed decisions about which diseases should be prioritised for clinical trials of novel treatments. The identification of these genes has greatly improved understanding of disease mechanisms, an essential prerequisite for developing new treatment approaches such as gene therapy.
Foal Immunodeficiency Syndrome (FIS) is an emerging fatal inherited equine disease which has caused much concern in the equine industry. Research at the University of Liverpool (UoL) into the genetic basis of this disease has identified the genetic mutation and developed a carrier test which led to equine population screening to understand the spread of this disease (>40% adult carriers in one breed, Fell ponies) and provided a tool for vets and owners to design selective breeding programmes to eradicate the disease. Since the introduction of the test in 2010, the number of cases has drastically fallen (only 1 detected in any breed in 2012) and FIS spread into other breeds is now considered most unlikely.
In genetic studies of human disease it is now routine for studies to collect genetic data on thousands of individuals with and without a particular disease. However, the genetic data collected is incomplete, with many millions of sites of the genome unmeasured. The novel methods and software (IMPUTE) developed by researchers at the University of Oxford predict unobserved genetic data using reference datasets.
IMPUTE has been adopted by the company Affymetrix in the design of custom genotyping chips. Affymetrix recently won the tenders by the UK Biobank and UKBiLEVE studies to genotype >500,000 participants, with a total study cost of ~£25M. The company states that IMPUTE gave their project bid a significant competitive advantage. Affymetrix also purchased the IMPUTE source code for £250,000. In addition, Roche Pharmaceuticals have used the software in their research on the genetic basis of drug response. The use of imputation has saved Roche ~$1,000,000.
Research at the UCL School of Pharmacy has positively influenced healthcare in startle disease/hyperekplexia, a rare disease that affects humans and several animal species, including dogs, horses and cattle. The identification and functional characterisation of mutations in genes involved in human startle disease by researchers at the School has improved genetic diagnostics and patient care. Our research on startle disease in cattle and dogs has also led to new non- invasive diagnostic tests that have alleviated animal suffering and reduced negative economic impacts on farmers. Overall, our findings have been translated into tangible benefits for the human and animal populations affected by this disease and have changed the way in which the disease is diagnosed and treated. We have also significantly increased the awareness of this rare disorder by communicating with academics, healthcare and veterinary professionals, and the general public.
As a result of research from Oxford's Professor Andrew Wilkie, accurate genetic diagnostic tests are now available for over 23% of all craniosynostosis cases nationally and internationally, leading to improved family planning and clinical management of this common condition worldwide. The premature fusion of cranial sutures, known as craniosynostosis, is a common developmental abnormality that occurs in 1 in 2,500 births. Over the past 20 years, the University of Oxford's Clinical Genetics Lab, led by Professor Wilkie in collaboration with the Oxford Craniofacial Unit, has identified more than half of the known genetic mutations that cause craniosynostosis and other malformations of the skull.
King's College London (KCL) has developed a generic test format which is being used to cheaply and easily detect a large number of single-gene disorders and chromosomal abnormalities in in vitro fertilised embryos — a highly significant impact. The test resulted from KCL's research to develop new strategies for preimplantation genetic diagnosis (PGD), which involved developing a small number of DNA probes targeted around a known area of genetic risk to identify mutations as well as methods to detect chromosomal translocations. Because the approach is cheap and easy to apply, it is being used by IVF clinics worldwide as well as by the NHS. The KCL/Guy's and St Thomas' Centre for PGD was licensed in 2008 by the UK Human Fertilisation and Embryo Authority to analyse over 50 genetic conditions affecting single genes and carries out more than half of all the UK's PGD testing. Embryos can now be tested using these techniques for virtually any inherited genetic disease prior to implantation with a 98% success rate, thus reducing the need for later prenatal diagnosis and termination of an affected foetus.
Research into the genetic causes of Parkinson's disease by Professor Nick Wood's group at the UCL Department of Molecular Neuroscience, describing the mutations in the gene LRRK2, have led to the development of a new genetic test which is now available to patients and their families. This benefits them by providing a precise diagnosis, and an understanding of the risk of disease to relatives. The research has provided new insight into patterns of Parkinson's disease in particular ethnic groups, and given rise to improved public understanding and high profile philanthropy. This discovery has also opened up a new area of research into disease-modifying treatments in Parkinson's disease within the pharmaceutical industry, leading to new drug candidates.
Age-related macular degeneration (AMD) is the most common cause of blindness in Western populations and reduces the quality of life of tens of millions of older people worldwide. In 2007 a research group at Cambridge University led by Professor John Yates in the Cambridge Institute for Medical Research discovered that a common genetic variant in the complement C3 gene was associated with an increased risk for AMD. This finding is now being used in a genetic test in North America and Europe to estimate individual risks for AMD. Those found to be at high risk are offered regular eye examinations to detect early development of the wet form of the disease before symptoms arise. This can be treated with anti-VEGF therapy. Early treatment gives the best chance of preserving sight by preventing irreversible damage to the retina.
Although individually infrequent, rare diseases collectively are a major health burden, particularly for individuals who suffer with conditions that are not routinely diagnosed or have no effective care pathways. Through the work of Professor Tim Barrett, the University of Birmingham is internationally recognised for translational research in rare inherited diabetes and obesity syndromes. This has had major impacts on patient care through gene identification for devastating multi-system syndromes; development of a unique international diagnostic testing service combining molecular testing with international clinical expertise; European reference centre status for three NHS highly specialised multidisciplinary services; and leadership of the European Registry for rare diabetes syndromes. Our national and international leadership for these previously poorly-served conditions has enabled sharing of best clinical practice, including development of clinics for Wolfram syndrome across the world.
Our research has had impact on the activities of practitioners and their services, health and welfare of patients, on society and on public policy. New diagnostic tests for genetic deafness have been introduced, and healthcare guidelines and professional standards adopted through our investigation of the aetiology of childhood-onset hearing loss. Disease prevention has been achieved by our research on antibiotic-associated deafness, public awareness of risk to health and hearing has been raised, and we have increased public engagement through debate on scientific and social issues. We have also influenced public policy on ethics of genetic testing for deafness with our research resulting in improved quality, accessibility and acceptability of genetic services among many hard-to-reach groups (deafblind, culturally Deaf, and the Bangladeshi population of East London).