Log in
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).
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 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.
Congenital disorders are causes of major morbidity and mortality worldwide. Using autozygosity mapping in a local community of Pakistani origin who have high rates of inherited recessive disorders due to consanguineous unions, we have identified more than 30 novel disease genes. Isolating these previously unknown molecular defects has enabled us to develop key diagnostic assays, subsequently provided by clinical laboratories globally. Our work has provided thousands of patients with a definitive diagnosis, removing the need for complex clinical testing. Those affected can be offered focused management and early therapeutic intervention as well as carrier and prenatal testing for themselves and family members. Our findings also provide new research opportunities for previously undefined diseases.
Long-standing research led by Prof. O'Rahilly (Department of Clinical Biochemistry) into the genetic and biochemical basis of severe insulin resistance syndromes, has led to improvements in diagnosis and care of patients internationally. These advances have facilitated revision of existing clinical classifications and implementation of novel diagnostic and management algorithms for these conditions. The clinical applicability of this research was recognised in 2011 by the Department of Health-England who have commissioned a national severe insulin resistance service in Cambridge, with support totalling ~£450,000 per annum.
Research from the University of Oxford's Clinical Genetics Laboratory initiated the introduction of an upper age limit of 40 years for sperm donors in the UK and internationally and led to increased public awareness of the effect of paternal age in the transmission of inherited disease. Oxford researchers, led by Professor Andrew Wilkie, were the first to describe the exclusively paternal transmission of de novo mutations, in a rare craniofacial disorder called Apert Syndrome; they also showed that the accumulation of such mutations leads to a disproportionate risk of disease transmission with age. By showing that the frequency of mutations increases with paternal age, this research contributed to important changes in clinical practice relating to sperm donation. This has also had a significant cultural impact, as the research and its clinical outcomes have challenged public perceptions of paternal age.
Impact: Health and welfare; policy and guidelines; public engagement. The identification of >20 genes linked to human developmental and childhood degenerative disorders.
Significance: Definitive diagnosis is essential for genetic counselling, prenatal screening and postnatal management.
Beneficiaries: People with developmental disorders and their families, prospective parents, the NHS and healthcare delivery organisations; public understanding of genetic disorders.
Attribution: Researchers from UoE identified/characterised all the genes described, and their mutation in disease.
Reach: Worldwide: these developmental disorders affect thousands of people. Genetic tests established as a result of the research are provided for people from 35 countries on all continents.
A routine service for genetic diagnosis of familial hypercholesterolaemia (FH) was developed and commissioned by the Northern Ireland Department of Health, based on the identification by the Queen's team of a series of mutations causing this condition. The team then developed novel diagnostic strategies that led to over 900 affected individuals being identified so that treatment could be delivered to them. Samples are received for diagnosis from the UK and Ireland and the work of the Centre helped to inform recent NICE guidance. The laboratory is recognised as an expert laboratory for the diagnosis of inherited lipid disorders by the International Federation for Clinical Chemistry and Laboratory Medicine.
Diagnostic tests have been successfully developed for identification of the cause of erythrocytosis, particularly in patients with unexplained forms of this rare disease. A diagnostic service with worldwide reach was developed for the genetic characterisation of patients that carry mutations identified by the Queens's group. It deals with approximately 100 samples per year referred for investigation for this rare disease from the UK, Europe and further afield. Proper diagnosis helps in management of patients with erythrocytosis where the problem is not mutation in one of the familiar causative genes. A pan-European web-based database has been established to collect information on long-term outcomes to inform patient management.
Ataxia telangiectasia (A-T) is an inherited disease affecting multiple systems in the body, causing severe disability and death. Work led by Professor Malcolm Taylor at the University of Birmingham has been central to the biological and clinical understanding of this disease, from the identification of the gene responsible to the clarification of related conditions with different underlying causes. As a result of this work, within the 2008-13 period, his laboratory has been designated the national laboratory for clinical diagnosis of A-T — a service also offered internationally — and has also changed national screening policy for breast cancer, following his confirmation of the increased risks of A-T patients and those who carry a single copy of the gene for this type of tumour. Furthermore, he has contributed in a major way to patient support for this condition.