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UK-Förderung (329.462 £): Identifizierung von Hauptrisiko-Allelen für Schizophrenie in blutsverwandten Familien Ukri01.06.2012 Forschung und Innovation im Vereinigten Königreich, Großbritannien
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Identifizierung von Hauptrisiko-Allelen für Schizophrenie in blutsverwandten Familien
| Zusammenfassung | Schizophrenia is a severely disabling mental illness that changes people's thought processes and the way they perceive the world around them. It is a common yet poorly understood condition which the World Health Organisation rates as equivalent to heart disease and cancer put together in terms of the disability it causes. It often persists throughout adult life, resulting in substantial costs to society, because patients remain unemployed and require ongoing care. Currently available medicines at best treat only some symptoms, don't work at all in around 30% of patients and are often associated with severe side-effects. In part, this is because we know so little about the root causes. However, we do know that much of the risk of developing schizophrenia is carried in our genes. By identifying the genetic defects involved, we can begin to piece together the complex jigsaw of genetic and environmental effects that combine to cause schizophrenia. Considerable effort has therefore been put into the identification of the genes involved. The approach used by most researchers so far, looking for an increase in the burden of small changes in genes in large groups of unrelated patients, has delivered only limited successes. Some hints of involvement for a handful of genes have been found, but these have generally not been confirmed by all the groups who have looked, so there remains much controversy and confusion around our genetic understanding of schizophrenia. We propose to use a much simpler method, namely looking at families in which several individuals have schizophrenia and determining what they have inherited in common that might have caused their illness. This approach presumes that, in at least some families, the disease is caused mainly by one gene defect which has a devastating effect on those who carry it. Other researchers have suggested that this approach will not work because schizophrenia is too complex, with the disease in any one person resulting from many genetic defects, each with only a small effect, combining with stresses in the environment to cause the disease. We suggest that previous searches for such "simple" schizophrenia families may have failed in the past because they were looking in the wrong population. We have looked in families from the Pakistani community of West Yorkshire, most of whom are the children of settlers who came to Bradford in the 1950s. This community is therefore likely to harbour a smaller range of mutations, but may have individual mutations with higher frequency, making them easier to find. Furthermore the Pakistani community of Bradford has a high level of marriage between cousins (consanguinity), which makes such mutations more likely to come together in children of related parents who carry the same mutation. We have already tried this approach in one family and it has worked spectacularly well, giving us strong evidence of the presence and location of a mutation on human chromosome 13 which, when an individual inherits two copies, is alone sufficient to cause schizophrenia. Others had already suggested the existence of such a gene but tentatively, and with only vague and differing suggestions as to its location. Our findings reveal the first compelling evidence for a "simple" genetic form of schizophrenia, and should now make it relatively easy for us to find the gene involved. We therefore seek funding, first to identify the actual gene and mutation, and then to repeat this search in more consanguineous Pakistani families, many of which we have already recruited or are recruiting, in order to locate and identify more genes mutated in schizophrenia. By studying these families we should be able to unequivocally track down at least some of the proteins involved and from that knowledge work out exactly what is going wrong. This will highlight pathways and processes that can then be targets for the development of novel therapies. |
| Kategorie | Research Grant |
| Referenz | MR/J004391/1 |
| Status | Closed |
| Laufzeit von | 01.06.2012 |
| Laufzeit bis | 31.08.2014 |
| Fördersumme | 329.462,00 £ |
| Quelle | https://gtr.ukri.org/projects?ref=MR%2FJ004391%2F1 |
Beteiligte Organisationen
| University of Leeds |
Die Bekanntmachung bezieht sich auf einen vergangenen Zeitpunkt, und spiegelt nicht notwendigerweise den heutigen Stand wider. Der aktuelle Stand wird auf folgender Seite wiedergegeben: University of Leeds, Leeds, Großbritannien.
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