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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.
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).
Research carried out by the University of Southampton into the genetic causes of diseases, and the gene mapping techniques and applications derived from this research, has benefited patients worldwide through improved prediction, diagnosis and treatment for common diseases with a complex genetic basis. A particularly striking example is age-related macular degeneration which is a common cause of blindness. Commercially, the research provides cost-effective strategies for genotyping DNA samples, and marker-based selection strategies for economically relevant animal species, such as cattle. The work underpins the development of the personal genomics industry, which specialises in individual genetic risk profiling.
Genetic tests introduced by insurance companies for dental healthcare in the USA are underpinned by leading research on the interleukin-1 cytokine system carried out at the University of Sheffield. Research in Sheffield has led directly to the development of these tests and has had [text removed for publication]. Implementation of the PSTf0d2 test by Delta Dental (largest dental insurer in the USA) stratifies patients at risk of periodontitis, has informed USA government policy on the use of genetic data in healthcare and has led directly to new dental policies for adults based on personalised IL-1 genetic data. The health value of this is $4.8 billion/year in the USA.
The International HapMap project was a major international research collaboration to map the structure of common human genetic variation across populations from Europe, Asia and Africa. Mathematical Scientists from the University of Oxford played key roles in the development of statistical methods for the project, along with its overall design and management of the International HapMap Project.
Companies have used HapMap as the primary resource to design genome-wide microarrays to make novel discoveries in, for example, pharmacogenetic studies. The size of this market is estimated at $1.25 billion.
One novel discovery has led to a genetic test that is predictive of sustained viral suppression in patients treated for chronic hepatitis C. An estimated 2.7 to 3.9 million people are affected by HCV infection. This test is sold commercially by the company LabCorp and is a significant contributor to the company's testing volume. Finally, the project has been important in widening the public understanding of genetic variation.
Research by Professor David Brook on inherited disorders has made a major contribution to the human genetics field. The work involved gene identification and mutation detection for genotype/phenotype correlation analysis in patients, which has led to the development of diagnostic tests for inherited conditions including myotonic dystrophy type 1 (DM1), Holt-Oram Syndrome (HOS), and campomelic dysplasia (CD). The tests have benefitted patients in the UK and throughout the rest of the world and in many cases they have been used as the definitive diagnostic measure. The assays developed have also been used in affected families for prenatal diagnosis to enable informed reproductive decisions.
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.
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.
Research by Professor Elizabeth Shephard at the UCL Research Department of Structural and Molecular Biology has led to identification of the genetic origin of Trimethylaminuria (TMAU), commonly known as fish-odour syndrome. This has led to genetic diagnosis and genetic counselling for TMAU in the UK, Europe, USA and Canada, and the publication of guidelines for treatment and diagnosis. Shephard has engaged closely with patient groups over the years to publicise her findings. There is now an increased understanding among medical practitioners and the public that the body odour produced is due to a metabolic defect of genetic origin, and is not due to poor hygiene.
Our research has established that Trimethylaminuria (TMAU) — a rare and distressing disorder where affected individuals excrete large amounts of odorous trimethylamine (TMA) in their breath, sweat and urine — is a genetic disorder, and is not, as previously thought, due to poor hygiene. This has transformed understanding in the medical community and the wider public of why some people have an extremely unpleasant `fishy' body odour, and has been crucial to helping individuals with TMAU who often suffer social isolation, rejection, depression and higher than normal suicide rates. The findings have led to genetic diagnosis and genetic counselling for TMAU in the UK, Europe, USA and Canada and the publication of guidelines for the diagnosis and treatment of the disorder.