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 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.
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
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
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
development of clinics for Wolfram syndrome across the world.
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.
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.
Identification of MUTYH by researchers at Cardiff University as
the first gene causing autosomal recessive colorectal cancer led to
international adoption of MUTYH genetic testing in the management
of familial colorectal cancer and thereby to global improvement in genetic
counselling and colorectal cancer prevention. Since 2008 MUTYH
gene testing has been introduced progressively and is now provided by at
least 84 European state and commercial diagnostic laboratories.
Commercialisation of testing in North America via a licence to Myriad
Genetics Inc. generated income of approximately $5M between 2008 and 2011
and licence fees and royalties to date of £331,947. Thus we claim impacts
in health and commercial benefit, the financial beneficiaries being Myriad
Genetics and Cardiff University.
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.
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 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
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.