A University College London scientist has led research to establish a database that could help other scientists identify which proteins to target when developing treatments for neurological conditions such as Alzheimer’s Disease. The database maps all of the genes operating in one section of the brain, and their ‘expression’ – the process of converting the genetic information encoded in DNA into a final gene product.
Professor John Hardy, UCL Institute of Neurology, conducted the research with Dr Amanda J. Myers at the University of Miami and researchers at the National Institute on Aging and the Translational Genome Research Institute.
“This is the world’s first catalogue of gene expression in the human brain and it shows there is a very high degree of genetic control in terms of how much of a particular protein is made by the genes in the brain” said Professor Hardy. “We’ve taken nearly 200 samples of the human brain and looked at how much of every gene in the genome is being made in a specific area in and around the frontal cortex. Then we looked at the expression pattern of the genes.”
Genetic studies frequently focus on finding candidate genes for neurological disorders. Typically, the genome is surveyed for genome variation that is over-represented within a collection of people at risk of disease, and some gene variants have been shown to pre-dispose to a particular disease. However, little is known about the biology behind these changes. Professor Hardy adds: “It is not just the presence of a particular gene but the amount of protein they produce which is going to have real significance in understanding and treating neurological disease. For example, work from our lab has linked a protein called MAPT with the neurological disease Progressive Supranuclear Palsy.
“The database resulting from this research has been made public and will allow researchers, when they find genetic risk factors for a disease, to refer to it and see whether the risk factor increases the amount of protein that the gene makes. In principle, though we are not there yet, this will allow researchers to take a blood sample from anyone and, from looking at their DNA sequence, know how much of every protein they make in their brain and what they might be more pre-disposed to in terms of neurological disease. This could help us understand the biological mechanisms at work, but could also be hugely useful in developing drugs to target those proteins and their associated diseases.”
Professor Hardy recently brought his pioneering neurological work back from the US to the UCL Institute of Neurology, Queen’s Square. He will be continuing the work detailed in this paper at the Institute. He said: “As we only looked at one area of the brain, the next logical step would be to perform the same process in a complete brain. It would be fantastic if it could eventually be done for the whole body – giving you an atlas of the human body in terms of gene expression. That would be an invaluable tool for scientists.”
Talking about his decision to return to the UK as Chair of Molecular Biology of Neurological Disease at the Institute, Professor Hardy said: “The job is the one I always wanted – the UCL Institute of Neurology is, quite simply, the best place for neurology in the world and to be able to come back here and work with clinicians and pathologists is fantastic. In the era of the genome you need two things: money and access to samples. British scientific research is now much better funded, particularly by the Wellcome Trust and the MRC, and because we have the NHS, and the Institute works alongside the National Hospital of Neurology and Neurosurgery, that means unprecedented access to samples.”
The paper ‘A survey of genetic human cortical gene expression’ is published in Nature Genetics.
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