Researchers at the University of Leeds aim to pin-point genetic defects involved in the development of schizophrenia within families.
Schizophrenia is a common yet poorly understood condition believed to be caused, in part, by genetic mutations. The two year project, funded by the Medical Research Council (MRC), builds on previous research at Leeds that suggests the existence of a genetic mutation, possibly causing an inherited form of the illness. "If we can confirm which specific genes and processes are at fault, we can start to develop new treatments to target them," says lead researcher Dr Steve Clapcote from the University's Faculty of Biological Sciences. "Our study is important because medicines currently used to treat schizophrenia aren't effective in about a third of patients and can also cause severe side effects," he added.
The £400,000 MRC grant funds a team of University of Leeds academics including biologist Dr Clapcote, geneticist Professor Chris Inglehearn and psychiatrist Dr Alistair Cardno, both from the University of Leeds' School of Medicine, and consultant psychiatrist Dr Tariq Mahmood of Leeds Partnerships NHS Foundation Trust. The team will initially be working with families from the Pakistani community of West Yorkshire, most of whom are the children of settlers from the 1950s. "We tend to find a smaller range of genetic mutations when individuals marry within a close-knit community, but it also means that we see certain mutations more often," says Professor Inglehearn.
The team believe that this new approach will allow them to narrow the search to uncover which mutated genes have been inherited that might cause the development of the illness. "In recent genetic studies of schizophrenia, researchers have usually studied large groups of unrelated people, looking for small increases in disease risk in a broad range of genes," says Dr Clapcote. "This new research uses a simpler approach, by working with a much smaller group of related patients," he explains.
The Leeds team has already tried this approach in one family, producing compelling evidence of the presence and location of a mutation on chromosome 13 which may cause a 'simple' genetic form of schizophrenia. They found that a child who inherits two copies of this mutation - usually from consanguineous marriage (marriage between cousins) - is more likely to develop the illness.
Previous research had suggested the existence of such a gene, but with vague and varied suggestions as to its exact location. Dr Clapcote believes that the team's preliminary work should make it easier to confirm and locate the gene involved. If successful, they plan to apply the new gene discovery approach to other families with multiple cases of schizophrenia. The identified genes may include suitable targets for new drugs, which the team is hopeful will treat the causes of the disease, not just the symptoms, and with fewer side effects.
Dr Clapcote is available for interview.
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Notes for Editors
The Faculty of Biological Sciences at the University of Leeds is one of the largest in the UK, with over 150 academic staff and over 400 postdoctoral fellows and postgraduate students. The Faculty is ranked 4th in the UK (Nature Journal, 457 (2009) doi :10.1038/457013a) based on results of the 2008 Research Assessment Exercise (RAE). The RAE feedback noted that "virtually all outputs were assessed as being recognized internationally, with many (60%) being internationally excellent or world-leading" in quality. The Faculty's research grant portfolio totals some £60M and funders include charities, research councils, the European Union and industry. http://www.fbs.leeds.ac.uk/
The University of Leeds is one of the largest higher education institutions in the UK with more than 30,000 students from 130 countries. With a turnover approaching £450m, Leeds is one of the top ten research universities in the UK, and a member of the Russell Group of research-intensive universities. It was placed 80th in the 2007 Times Higher Education world universities league table. The University's vision is to secure a place among the world's top 50 by 2015. http://www.leeds.ac.uk/
For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including the first antibiotic penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. http://www.mrc.ac.uk/