HTS - Maximising the value of MRC Brain Banks

Lead Research Organisation: University of Edinburgh
Department Name: UNLISTED

Abstract

The aim of this study to maximise the value of the brain tissue samples available to the research community in the four MRC-funded brain banks by the systematic analysis and integration of data from genomic studies on cases currently available for research in the banks. . All MRC brain banks have ethics approval to function as tissue banks and to collect, store and release tissue samples and data from consented donors. Consent/authorisation for genetic research is recorded and will be used to identify cases for inclusion in this study. Governance mechanisms include local NHS governance, Human Tissue Authority licences and Healthcare Improvement Scotland accreditation, along with MRC policies on research governance.
This study will involve the investigation of normal brains from a wide age range and brains from well-characterised disease cohorts in the MRC brain banks. We aim to genetically characterise 1500 representative brains with Alzheimer disease, dementia with Lewy bodies /Parkinson disease, vascular dementia, frontotemporal dementia/motor neurone disease, Creutzfeldt-Jakob disease and controls. The data generated will greatly enrich the clinical and neuropathological data currently associated with these samples. This work will therefore provide major added value to the exiting brain banks, opening up totally new opportunities for mechanistic and translational research in neurodegeneration and brain aging.

Technical Summary

The aim of this study to maximise the value of the brain tissue samples available to the research community in the four MRC-funded brain banks by the systematic analysis and integration of data from genomic studies on cases currently available for research in the banks. . All MRC brain banks have ethics approval to function as tissue banks and to collect, store and release tissue samples and data from consented donors. Consent/authorisation for genetic research is recorded and will be used to identify cases for inclusion in this study. Governance mechanisms include local NHS governance, Human Tissue Authority licences and Healthcare Improvement Scotland accreditation, along with MRC policies on research governance.
This study will involve the investigation of normal brains from a wide age range and brains from well-characterised disease cohorts in the MRC brain banks. We aim to genetically characterise 1500 representative brains with Alzheimer disease, dementia with Lewy bodies /Parkinson disease, vascular dementia, frontotemporal dementia/motor neurone disease, Creutzfeldt-Jakob disease and controls. The data generated will greatly enrich the clinical and neuropathological data currently associated with these samples. This work will therefore provide major added value to the exiting brain banks, opening up totally new opportunities for mechanistic and translational research in neurodegeneration and brain aging. This work links strategic priorities of MRC and the NHS: understanding dementia and the role of genetics in disease.
The MRC brain banks in Edinburgh, Kings College, Newcastle and Oxford will all contribute tissue samples to this study to maximise throughput. Rapid progress will be ensured by the experience of the investigators, the substantial research infrastructure in all four centres, the existing availability of very large numbers of high quality frozen and fixed tissue samples in the MRC Brain Banks, and by outsourcing both nucleic acid extraction and sequencing, with in-house bioinformatics. All raw data generated will be stored in a secure database and made openly available to researchers using samples from the brain banks. In the short term, the data generated is likely to lead to the identification of new highly-penetrant neurodegenerative disease genes and novel disease phenotypes. In the longer term, the data will also will provide a unique resource to help the international research community define the role and clinicopathological spectrum of known genetic causes of neurodegeneration, enable the genetic recall of brain tissue by international research groups studying neurodegeneration and allow researchers to formulate novel hypotheses based on the data from this “deep genotyping” approach.

Publications

10 25 50

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Wei W (2019) Frequency and signature of somatic variants in 1461 human brain exomes. in Genetics in medicine : official journal of the American College of Medical Genetics

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Keogh MJ (2018) Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains. in Journal of neurology, neurosurgery, and psychiatry

 
Description MRC Network of UK Brain Banks 
Organisation Cambridge University Hospitals NHS Foundation Trust
Department Cambridge Brain Bank
Country United Kingdom 
Sector Public 
PI Contribution I have created a Network of Brain Banks in the UK, involving 10 different centres, to imrpove the standards of operation and to increase the use of huuman brain tissue in Neuroscience research
Collaborator Contribution Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.
Impact Creation of a Network with a Steering Committee, Management group, Users Group and Website. Interface with other UK funders of brain banks including Parkinson's UK, the Multiple Sclerosis Society, the Alzheimer Society and the Alzheimer Research Trust.
Start Year 2009
 
Description MRC Network of UK Brain Banks 
Organisation Imperial College London
Department Multiple Sclerosis and Parkinson's Tissue Bank
Country United Kingdom 
Sector Academic/University 
PI Contribution I have created a Network of Brain Banks in the UK, involving 10 different centres, to imrpove the standards of operation and to increase the use of huuman brain tissue in Neuroscience research
Collaborator Contribution Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.
Impact Creation of a Network with a Steering Committee, Management group, Users Group and Website. Interface with other UK funders of brain banks including Parkinson's UK, the Multiple Sclerosis Society, the Alzheimer Society and the Alzheimer Research Trust.
Start Year 2009
 
Description MRC Network of UK Brain Banks 
Organisation King's College London
Department Institute of Psychiatry, Psychology & Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution I have created a Network of Brain Banks in the UK, involving 10 different centres, to imrpove the standards of operation and to increase the use of huuman brain tissue in Neuroscience research
Collaborator Contribution Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.
Impact Creation of a Network with a Steering Committee, Management group, Users Group and Website. Interface with other UK funders of brain banks including Parkinson's UK, the Multiple Sclerosis Society, the Alzheimer Society and the Alzheimer Research Trust.
Start Year 2009
 
Description MRC Network of UK Brain Banks 
Organisation Newcastle University
Department Institute for Ageing and Health
Country United Kingdom 
Sector Academic/University 
PI Contribution I have created a Network of Brain Banks in the UK, involving 10 different centres, to imrpove the standards of operation and to increase the use of huuman brain tissue in Neuroscience research
Collaborator Contribution Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.
Impact Creation of a Network with a Steering Committee, Management group, Users Group and Website. Interface with other UK funders of brain banks including Parkinson's UK, the Multiple Sclerosis Society, the Alzheimer Society and the Alzheimer Research Trust.
Start Year 2009
 
Description MRC Network of UK Brain Banks 
Organisation University College London
Department Institute of Neurology
Country United Kingdom 
Sector Academic/University 
PI Contribution I have created a Network of Brain Banks in the UK, involving 10 different centres, to imrpove the standards of operation and to increase the use of huuman brain tissue in Neuroscience research
Collaborator Contribution Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.
Impact Creation of a Network with a Steering Committee, Management group, Users Group and Website. Interface with other UK funders of brain banks including Parkinson's UK, the Multiple Sclerosis Society, the Alzheimer Society and the Alzheimer Research Trust.
Start Year 2009
 
Description MRC Network of UK Brain Banks 
Organisation University of Bristol
Department School of Clinical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution I have created a Network of Brain Banks in the UK, involving 10 different centres, to imrpove the standards of operation and to increase the use of huuman brain tissue in Neuroscience research
Collaborator Contribution Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.
Impact Creation of a Network with a Steering Committee, Management group, Users Group and Website. Interface with other UK funders of brain banks including Parkinson's UK, the Multiple Sclerosis Society, the Alzheimer Society and the Alzheimer Research Trust.
Start Year 2009
 
Description MRC Network of UK Brain Banks 
Organisation University of Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution I have created a Network of Brain Banks in the UK, involving 10 different centres, to imrpove the standards of operation and to increase the use of huuman brain tissue in Neuroscience research
Collaborator Contribution Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.
Impact Creation of a Network with a Steering Committee, Management group, Users Group and Website. Interface with other UK funders of brain banks including Parkinson's UK, the Multiple Sclerosis Society, the Alzheimer Society and the Alzheimer Research Trust.
Start Year 2009
 
Description MRC Network of UK Brain Banks 
Organisation University of Manchester
Department Community-Based Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution I have created a Network of Brain Banks in the UK, involving 10 different centres, to imrpove the standards of operation and to increase the use of huuman brain tissue in Neuroscience research
Collaborator Contribution Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.
Impact Creation of a Network with a Steering Committee, Management group, Users Group and Website. Interface with other UK funders of brain banks including Parkinson's UK, the Multiple Sclerosis Society, the Alzheimer Society and the Alzheimer Research Trust.
Start Year 2009
 
Description MRC Network of UK Brain Banks 
Organisation University of Oxford
Department Oxford Centre for Human Brain Activity (OHBA)
Country United Kingdom 
Sector Academic/University 
PI Contribution I have created a Network of Brain Banks in the UK, involving 10 different centres, to imrpove the standards of operation and to increase the use of huuman brain tissue in Neuroscience research
Collaborator Contribution Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.
Impact Creation of a Network with a Steering Committee, Management group, Users Group and Website. Interface with other UK funders of brain banks including Parkinson's UK, the Multiple Sclerosis Society, the Alzheimer Society and the Alzheimer Research Trust.
Start Year 2009
 
Description MRC Network of UK Brain Banks 
Organisation University of Sheffield
Department Department of Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution I have created a Network of Brain Banks in the UK, involving 10 different centres, to imrpove the standards of operation and to increase the use of huuman brain tissue in Neuroscience research
Collaborator Contribution Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.Collaboration in Network activities.
Impact Creation of a Network with a Steering Committee, Management group, Users Group and Website. Interface with other UK funders of brain banks including Parkinson's UK, the Multiple Sclerosis Society, the Alzheimer Society and the Alzheimer Research Trust.
Start Year 2009