image: An international research collaboration has shed new light on how DNA sequence variation can influence gene activity in the developing human brain. view more
Credit: Helen Spears
An international research collaboration has shed new light on how DNA sequence variation can influence gene activity in the developing human brain.
The team, which was led by researchers at the University of Exeter Medical School, King's College London and Cardiff University, conducted the first study of how genetic variation influences DNA methylation, an epigenetic modification that can have direct effects on gene expression and function, in the developing brain. In research published in Nature Neuroscience and funded by the Medical Research Council, they demonstrated the potential utility of such data for refining the genetic signals associated with diseases hypothesised to have a neurodevelopmental component, such as schizophrenia.
DNA methylation is a chemical modification to one of the four bases that make up our genetic code, controlling when and where genes are expressed. As with other epigenetic marks, it is known to be dynamic across the life course and modifiable by a number of factors, including the underlying genetic sequence. It represents one possible pathway between genetic variation and disease, with genetic differences altering the regulation of gene expression at specific points in development. In this study the authors found that genetic variants associated with schizophrenia were enriched for changes that impact upon DNA methylation in the developing brain. It is of particular interest that some of the genetic risk factors for schizophrenia are associated with differences in DNA methylation as early as the first and second trimester of life.
Dr Eilis Hannon, of the University of Exeter Medical School, commented: "This data has particular relevance for disorders such as schizophrenia, where it is thought that changes early in brain development increase an individual's liability to develop the illness later on in life. Therefore understanding the genetic effects of risk variants on gene regulation during the earliest stages of brain development may point us towards the underlying biology of schizophrenia."
Professor Jonathan Mill, of the University of Exeter Medical School, who led the study, said: "This study builds on the tremendous advances in identifying the genetic risks for schizophrenia in the last couple of years. We have shown that genetic variation can have significant effects on gene regulation during brain development, with important implications for understanding the origins of schizophrenia and other disorders with a neurodevelopmental component."
The data is freely available to the wider research community via an online database (see http://epigenetics.essex.ac.uk/mQTL/) and will potentially facilitate the interpretation of genetic findings in studies of other neurodevelopmental disorders.
The research team was led by the University of Exeter Medical School in a collaboration involving researchers from King's College London, the Garvan Institute of Medical Research in Australia, the MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, the University of Essex, and the Douglas Mental Health Institute, Canada.
###
About the University of Exeter Medical School
The University of Exeter Medical School is improving the health of the South West and beyond, through the development of high quality graduates and world-leading research that has international impact.
As part of a Russell Group university, we combine this world-class research with very high levels of student satisfaction. The University of Exeter Medical School's Medicine programme is ranked 11th in the Guardian University Guide 2016. Exeter has over 19,000 students and is one of the global top 100 universities according to the Times Higher Education World University Rankings 2015-16, positioned 93rd. Exeter is also ranked 7th in The Times and The Sunday Times Good University Guide 2016, 9th in the Guardian University Guide 2016 and 10th in The Complete University Guide 2016. In the 2014 Research Excellence Framework (REF), the University ranked 16th nationally, with 98% of its research rated as being of international quality. Exeter's Clinical Medicine research was ranked 3rd in the country, based on research outputs that were rated world-leading. Public Health, Health Services and Primary Care research also ranked in the top ten, in joint 9th for research outputs rated world-leading or internationally excellent. Exeter was named The Times and The Sunday Times Sports University of the Year 2015-16, in recognition of excellence in performance, education and research. Exeter was The Sunday Times University of the Year 2012-13.
http://www.exeter.ac.uk/Medicine
For further information:
Louise Vennells
Communications Manager
University of Exeter Medical School
+44 (0)1392 724927 or 07768 511866
l.vennells@exeter.ac.uk
Journal
Nature Neuroscience