Using Next Generation Sequencing to Unravel the Pathogenesis of Sporadic Inclusion Body Myositis - The International IBM Consortium Genetic Study
Lead Research Organisation:
University College London
Department Name: Institute of Neurology
Abstract
The commonest muscle disease that occurs in patients over the age of 45 years is a muscle wasting disease called inclusion body myositis (IBM). Patients typically develop progressive muscle wasting and weakness that progresses and causes marked disability and ultimately death from immobility over the course of around 10 years. There are no effective treatment for patients with IBM. The precise cause of this muscle disease is not known. However, on muscle biopsies from patients there seems to be a combination of some mild inflammation in the muscle and also an accumulation of abnormal proteins, similar to the accumulated proteins that are seen in the brains of patients with neurodegenerative diseases such as Alzheimer's, fronto-temporal dementia and motor neurone disease.
Previous research has indicated that there may be genetic factors that predispose people to getting IBM but the previous studies have been quite small and not conclusive. In this research we have brought together experts in IBM from all over the world including Europe, USA and Australia to generate increased awareness of IBM, define diagnostic criteria, collect clinical information and DNA. Over the last three years we have been able to collect the largest group ever of IBM patients and DNA samples - approximately 950 cases and this number will be over 1000 once this study begins. The patient DNA and muscle tissue has been carefully stored for this work. This very large collection of DNA has put us in a very good position to undertake much more detailed genetic studies than have ever been done before to try and work out what the genetic risks factors and genes are that predispose people to this devastating disease.
We plan to use the latest next generation sequencing techniques to unravel all the coding variants (those that alter proteins) that are present in 200 IBM patients DNA samples in comparison with 200 patients that are controls with normal muscles. We will analyze the DNA that we have already extracted from patients muscle tissue as this is the best diagnostic group. We will replicate the variants found in a further 700 IBM cases and over 2200 other controls. We are highly experienced in next generation sequencing technology and this has been strengthened by the recent award of a Wellcome Trust equipment grant to purchase the latest next generation sequencer. Recently we have used these techniques to identify the genetic causes of other neuromuscular disorders.
In comparison with other disorders like Alzheimer's disease, where proteins are aggregated in the brain as opposed to the muscle as in IBM, the greatest advancement have been made with the identification of disease genes and genetic risk factors. If we can work out what the key genes are and how these disease causing pathways function, we will pave the way for new therapies and treatments to help patients.
Previous research has indicated that there may be genetic factors that predispose people to getting IBM but the previous studies have been quite small and not conclusive. In this research we have brought together experts in IBM from all over the world including Europe, USA and Australia to generate increased awareness of IBM, define diagnostic criteria, collect clinical information and DNA. Over the last three years we have been able to collect the largest group ever of IBM patients and DNA samples - approximately 950 cases and this number will be over 1000 once this study begins. The patient DNA and muscle tissue has been carefully stored for this work. This very large collection of DNA has put us in a very good position to undertake much more detailed genetic studies than have ever been done before to try and work out what the genetic risks factors and genes are that predispose people to this devastating disease.
We plan to use the latest next generation sequencing techniques to unravel all the coding variants (those that alter proteins) that are present in 200 IBM patients DNA samples in comparison with 200 patients that are controls with normal muscles. We will analyze the DNA that we have already extracted from patients muscle tissue as this is the best diagnostic group. We will replicate the variants found in a further 700 IBM cases and over 2200 other controls. We are highly experienced in next generation sequencing technology and this has been strengthened by the recent award of a Wellcome Trust equipment grant to purchase the latest next generation sequencer. Recently we have used these techniques to identify the genetic causes of other neuromuscular disorders.
In comparison with other disorders like Alzheimer's disease, where proteins are aggregated in the brain as opposed to the muscle as in IBM, the greatest advancement have been made with the identification of disease genes and genetic risk factors. If we can work out what the key genes are and how these disease causing pathways function, we will pave the way for new therapies and treatments to help patients.
Technical Summary
1. Library preparation for exome sequencing
In each case high quality DNA (A260/280 ratio >1.8) has been extracted. We have switched over to the Illumina TruSeq Enrichment Kit as it allows six samples to be pooled for exome sequencing and is therefore far more cost effective. The enrichment method is a standard protocol from Illumina starting with the TruSeq sample preparation, pooling of six samples, capture of targeted regions with the TruSeq exome kit and then sequencing. The HiSeq has a very large capacity for sequencing, with the TruSeq enrichment our current most cost effective run is 100bp paired-end reads which gives 60 million reads per sample, at around 68 fold coverage (2 samples per lane). Depending on cost we can modify the runs in several ways, usually by extending read length and changing samples per lane.
2. Exome sequence data processing and variant calling
After the genome analyser generates the raw sequencing images (image analysis) there are several steps involved in the read conversion to variant calling. These include initial base calling, sequence alignment, building, indexing, sorting SAM files, recalibrating quality scores, removing duplicates and merging lanes. Variants are called and filtered based on quality control (read depth, quality scores etc). A genotype file is produced and then annotation and prediction of consequence (amino-acid change, predicted damage of variant) is carried out using the package Sorting Intolerant From Tolerant (SIFT).
3. Statistical analysis
This will primarily focus on gene level comparisons testing a reduced set of genes identified as harbouring non-synonymous coding variants or splice variants that may contribute to risk of IBM. Exome sequence data will be filtered first to remove common variants found in publicly available data from dbSNP and the 1000 Genomes Project. A second level of filtering will be used to extract non-synonymous coding variants and splice variants using existing exome annota
In each case high quality DNA (A260/280 ratio >1.8) has been extracted. We have switched over to the Illumina TruSeq Enrichment Kit as it allows six samples to be pooled for exome sequencing and is therefore far more cost effective. The enrichment method is a standard protocol from Illumina starting with the TruSeq sample preparation, pooling of six samples, capture of targeted regions with the TruSeq exome kit and then sequencing. The HiSeq has a very large capacity for sequencing, with the TruSeq enrichment our current most cost effective run is 100bp paired-end reads which gives 60 million reads per sample, at around 68 fold coverage (2 samples per lane). Depending on cost we can modify the runs in several ways, usually by extending read length and changing samples per lane.
2. Exome sequence data processing and variant calling
After the genome analyser generates the raw sequencing images (image analysis) there are several steps involved in the read conversion to variant calling. These include initial base calling, sequence alignment, building, indexing, sorting SAM files, recalibrating quality scores, removing duplicates and merging lanes. Variants are called and filtered based on quality control (read depth, quality scores etc). A genotype file is produced and then annotation and prediction of consequence (amino-acid change, predicted damage of variant) is carried out using the package Sorting Intolerant From Tolerant (SIFT).
3. Statistical analysis
This will primarily focus on gene level comparisons testing a reduced set of genes identified as harbouring non-synonymous coding variants or splice variants that may contribute to risk of IBM. Exome sequence data will be filtered first to remove common variants found in publicly available data from dbSNP and the 1000 Genomes Project. A second level of filtering will be used to extract non-synonymous coding variants and splice variants using existing exome annota
Planned Impact
Who will benefit
Importance and unmet health need for patients and the economy: Inclusion body myositis is the most common acquired muscle disease in patients over the age of forty years. It causes progressive major disability and often premature death after 5-10 years from the consequences of immobility. It represents a significant unmet health need in the UK-worldwide. Since onset is often in prime working life and patients often become significantly disabled quickly and cannot contribute to the economy. A systematic genetic study using the latest genetic technology has not been undertaken. Limited studies have suggested a HLA association, however the disease is unresponsive to immunosuppression and discovery of new mechanisms pathways is required. Key beneficiaries from this research include 1. The immediate and wider science communities, 2. Key established and new industry partners who can develop new paradigms for drug testing based on new genetic discovery 3. Patient organisations and patients. Until now IBM patients have been a relatively neglected group experiencing delayed and misdiagnosis. Professor Hanna and the MRC Centre for translational research have existing partnerships with the major patient organisations linked to IBM namely the myositis support group where Professor Hanna is an advisor helped plan annual patient meetings and the Muscular Dystrophy Campaign that also support IBM patient groups.
How will they benefit
Potential areas for exploitation from this research: Discovery of new genetic associations for IBM will have significant potential to build on existing collaborations with industry and develop new industry collaborations. Potential new areas arising from this research include- identification of new target pathways that might be druggable, the possibility of developing new or taking advantage of existing animal models and of developing new cellular models. All these possibilities will be of interest to industry especially for testing new therapies based on the genetic discovery of new targets. We have established collaborations with the Senexis (Cambridge biotech) to screen anti protein aggregate small molecules and we are currently using a nematode and a myoblast line for screening. However, Senexis- (see MRC Centre Senexis collaboration at www.cnmd.ac.uk) have access to very large number of potential agents- new genetic discovery could direct selection. We have an existing collaboration with Cytrx USA and completing a proof of principle heat shock protein upregulation experimental medicine study in IBM- this relationship will be developed by new genetic discovery. New IBM genetic associations has potential for new genetic testing paradigms for risk stratification and potential for commercialisation of genetic testing.
With Patients and Patient Organisations- the MRC Centre for Neuromuscular Diseases has established effective and regular communication channels with the key patient groups representing IBM. Results of this research along with implications and impact for patients and families will be discussed at the annual Myositis Support Group meeting, the annual MRC Centre patient group meeting and the Muscular Dystrophy Campaign patient group meetings and local branch meetings. All our latest IBM research is posted on the MRC Centre website, the MDC website and the Myositis support group newsletter. With policy makers and NHS commissioners-Professor Hanna is actively engaged with the cross party parliamentary group for neuromuscular diseases including IBM and has given evidence in parliament about the impact of neuromuscular diseases including IBM and has worked with this group and the commissioners to develop standards of care for patients- this work is ongoing and can include implications of this genetic research discovery for patient care eg genetic risk assessment.
Importance and unmet health need for patients and the economy: Inclusion body myositis is the most common acquired muscle disease in patients over the age of forty years. It causes progressive major disability and often premature death after 5-10 years from the consequences of immobility. It represents a significant unmet health need in the UK-worldwide. Since onset is often in prime working life and patients often become significantly disabled quickly and cannot contribute to the economy. A systematic genetic study using the latest genetic technology has not been undertaken. Limited studies have suggested a HLA association, however the disease is unresponsive to immunosuppression and discovery of new mechanisms pathways is required. Key beneficiaries from this research include 1. The immediate and wider science communities, 2. Key established and new industry partners who can develop new paradigms for drug testing based on new genetic discovery 3. Patient organisations and patients. Until now IBM patients have been a relatively neglected group experiencing delayed and misdiagnosis. Professor Hanna and the MRC Centre for translational research have existing partnerships with the major patient organisations linked to IBM namely the myositis support group where Professor Hanna is an advisor helped plan annual patient meetings and the Muscular Dystrophy Campaign that also support IBM patient groups.
How will they benefit
Potential areas for exploitation from this research: Discovery of new genetic associations for IBM will have significant potential to build on existing collaborations with industry and develop new industry collaborations. Potential new areas arising from this research include- identification of new target pathways that might be druggable, the possibility of developing new or taking advantage of existing animal models and of developing new cellular models. All these possibilities will be of interest to industry especially for testing new therapies based on the genetic discovery of new targets. We have established collaborations with the Senexis (Cambridge biotech) to screen anti protein aggregate small molecules and we are currently using a nematode and a myoblast line for screening. However, Senexis- (see MRC Centre Senexis collaboration at www.cnmd.ac.uk) have access to very large number of potential agents- new genetic discovery could direct selection. We have an existing collaboration with Cytrx USA and completing a proof of principle heat shock protein upregulation experimental medicine study in IBM- this relationship will be developed by new genetic discovery. New IBM genetic associations has potential for new genetic testing paradigms for risk stratification and potential for commercialisation of genetic testing.
With Patients and Patient Organisations- the MRC Centre for Neuromuscular Diseases has established effective and regular communication channels with the key patient groups representing IBM. Results of this research along with implications and impact for patients and families will be discussed at the annual Myositis Support Group meeting, the annual MRC Centre patient group meeting and the Muscular Dystrophy Campaign patient group meetings and local branch meetings. All our latest IBM research is posted on the MRC Centre website, the MDC website and the Myositis support group newsletter. With policy makers and NHS commissioners-Professor Hanna is actively engaged with the cross party parliamentary group for neuromuscular diseases including IBM and has given evidence in parliament about the impact of neuromuscular diseases including IBM and has worked with this group and the commissioners to develop standards of care for patients- this work is ongoing and can include implications of this genetic research discovery for patient care eg genetic risk assessment.
Organisations
- University College London (Lead Research Organisation, Project Partner)
- Ataxia UK (Collaboration)
- National and Kapodistrian University of Athens (Collaboration)
- Sarah Matheson Trust for MSA (Collaboration)
- British Medical Association (BMA) (Collaboration)
- Partnership for Advanced Computing in Europe (PRACE) (Collaboration)
- University of Pennsylvania (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- Wayne State University (Collaboration)
- University College London (Collaboration)
- Sakhalin State University (Collaboration)
- National Organization for Rare Disorders (NORD) (Collaboration)
- University Of Thessaly (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- University of Tehran (Collaboration)
- Genomics England (Collaboration)
- National Institutes of Health (NIH) (Collaboration)
- European Commission (Collaboration)
- Thomas Jefferson University (Project Partner)
- NEWCASTLE UNIVERSITY (Project Partner)
- Sorbonne University (Project Partner)
- University of Southern California (Project Partner)
- Catholic University of the Sacred Heart (Project Partner)
- University of Southampton (Project Partner)
- Salford Royal Hospital (Project Partner)
- University of Manchester (Project Partner)
- University of Kansas Medical Center (Project Partner)
- University of Western Australia (Project Partner)
- Brigham and Women's Hospital (Project Partner)
- West Suffolk Hospital (Project Partner)
- The Ohio State University (Project Partner)
- University of Rochester (Project Partner)
- Imperial College Healthcare NHS Trust (Project Partner)
- Pitié-Salpêtrière Hospital (Project Partner)
Publications
Gardiner AR
(2015)
The clinical and genetic heterogeneity of paroxysmal dyskinesias.
in Brain : a journal of neurology
Kiely AP
(2015)
Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation.
in Molecular neurodegeneration
Paudel R
(2015)
Neuropathology of Beta-propeller protein associated neurodegeneration (BPAN): a new tauopathy.
in Acta neuropathologica communications
Hufnagel RB
(2015)
Neuropathy target esterase impairments cause Oliver-McFarlane and Laurence-Moon syndromes.
in Journal of medical genetics
Gang Q
(2015)
The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis.
in Neurobiology of aging
Koutsis G
(2015)
A novel ABCD1 mutation detected by next generation sequencing in presumed hereditary spastic paraplegia: A 30-year diagnostic delay caused by misleading biochemical findings.
in Journal of the neurological sciences
Khaleeli Z
(2015)
A novel HTRA1 exon 2 mutation causes loss of protease activity in a Pakistani CARASIL patient.
in Journal of neurology
Mencacci NE
(2015)
ADCY5 mutations are another cause of benign hereditary chorea.
in Neurology
Erro R
(2015)
H-ABC syndrome and DYT4: Variable expressivity or pleiotropy of TUBB4 mutations?
in Movement disorders : official journal of the Movement Disorder Society
Description | Improved and larger range of neurogenetic tests |
Geographic Reach | National |
Policy Influence Type | Influenced training of practitioners or researchers |
Impact | Improved and larger range of neurogenetic tests. This leads to greater research and a better service for patients |
Description | BMA project grant |
Amount | £21,000 (GBP) |
Organisation | British Medical Association (BMA) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2007 |
End | 01/2010 |
Description | CRBC project grant/CRBC |
Amount | £98,000 (GBP) |
Organisation | National Institute for Health Research |
Department | UCLH/UCL Biomedical Research Centre |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2009 |
End | 05/2011 |
Description | Equipment award Wellcome Trust |
Amount | £661,363 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 07/2011 |
End | 07/2016 |
Description | MRC Project Grant |
Amount | £522,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2011 |
End | 01/2015 |
Description | MRC Research Grant (The Pathophysiology of Spinocerebellar degeneration) |
Amount | £1,600,000 (GBP) |
Funding ID | G0802760 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 02/2010 |
End | 01/2015 |
Description | MYOPROSP Consortium |
Amount | £66,301 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start |
Description | PhD studentship to work on IBM and neuromuscular disorders from the Saudi Government |
Amount | £150,000 (GBP) |
Organisation | Government of Saudi Arabia |
Sector | Public |
Country | Saudi Arabia |
Start | 08/2016 |
End | 09/2020 |
Description | Project grant: A randomised controlled trial of efficacy of heat shock protein upregulation in IBM |
Amount | $1,543,444 (USD) |
Organisation | Food and Drug Administration (FDA) |
Sector | Public |
Country | United States |
Start |
Description | Proof of concept trial |
Amount | $100,000 (USD) |
Organisation | Higher Education Funding Council for England |
Sector | Public |
Country | United Kingdom |
Start | 04/2016 |
End | 07/2016 |
Description | UCL CBRC equipment grant |
Amount | £339,000 (GBP) |
Organisation | National Institute for Health Research |
Department | UCLH/UCL Biomedical Research Centre |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2011 |
End | 08/2016 |
Description | Wellcome Trust Equipment Grant |
Amount | £661,363 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 07/2011 |
End | 08/2016 |
Description | Wellcome Trust Strategic Award |
Amount | £980,000 (GBP) |
Funding ID | The Wellcome Trust (equipment and the Synaptopathies strategic award (104033/z/14/z) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2015 |
End | 04/2020 |
Title | Genome sequencing and GeCIP |
Description | Genome sequencing and GeCIP |
Type Of Material | Technology assay or reagent |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | Genome sequencing and GeCIP |
URL | http://www.genomicsengland.co.uk |
Title | Muscle international registry and biobank |
Description | Muscle international registry and biobank |
Type Of Material | Database/Collection of Data/Biological Samples |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | Muscle international registry and biobank |
Title | Synaptopathies collaboration |
Description | Synaptopathies collaboration |
Type Of Material | Biological samples |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | Synaptopathies collaboration |
Title | SOLVE-RD, Coriell, Neurobiobank database of samples, tissue |
Description | SOLVE-RD, Coriell, Neurobiobank database of samples, tissue: all anonymous Important for genetics and analysis |
Type Of Material | Database/Collection of data |
Provided To Others? | No |
Impact | SOLVE-RD, Coriell, Neurobiobank database of samples, tissue: all anonymous Important for genetics and analysis |
Title | Synaptopathies collaboration |
Description | Synaptopathies collaboration |
Type Of Material | Database/Collection of data |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | Synaptopathies collaboration |
Description | Ataxia UK |
Organisation | Ataxia UK |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Information and genetic analysis of patients |
Collaborator Contribution | Made members aware of our work, identified patients and families |
Impact | Publications, made UK patients with Ataxia more aware |
Start Year | 2006 |
Description | Athens collaboration on ataxia and neuropathy |
Organisation | National and Kapodistrian University of Athens |
Department | Neurology Athens |
Country | Greece |
Sector | Academic/University |
PI Contribution | Large Greek study on ataxia and neuropathy in Greece |
Impact | Large Greek study on ataxia and neuropathy in Greece |
Start Year | 2010 |
Description | BMA |
Organisation | British Medical Association (BMA) |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Funding and publication |
Collaborator Contribution | Funding and good press for our research |
Impact | Funding and publication |
Start Year | 2007 |
Description | Cambridge collaboration on Dog ataxia and neuropathy. |
Organisation | University of Cambridge |
Department | Department of Veterinary Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Cambridge collaboration on Dog ataxia and neuropathy. We are working on the genetics of neuropathy and ataxia in dog models of human disease |
Collaborator Contribution | Dog tissue |
Impact | Ongoing work |
Start Year | 2010 |
Description | EUROSCA |
Organisation | European Commission |
Department | EC FP6 Collaborative Projects |
Country | European Union (EU) |
Sector | Academic/University |
PI Contribution | Identification, screening and functional characterization of ataxia genes |
Collaborator Contribution | EUROSCA is a collaboration between researchers and clinicians working on ataxia. These has brought cases and techniques that have benefited my research. |
Impact | Publications as already give. Patients and clinical details of cases with ataxia |
Start Year | 2006 |
Description | European Brain Bank Network |
Organisation | Medical Research Council (MRC) |
Department | MRC UK Brain Banks Network |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Brain tissue for our research |
Collaborator Contribution | Brain tissue for research |
Impact | Brain tissue for our research |
Start Year | 2006 |
Description | European and American Brain Bank Network |
Organisation | Medical Research Council (MRC) |
Department | MRC UK Brain Banks Network |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This collaboration has given valuable patient brain tissue to our research |
Collaborator Contribution | Collaborated with tissus |
Impact | Publications and the addition of important tissue resources |
Start Year | 2006 |
Description | Genomics England (GEL) 100,000 genomes project: population diversity project |
Organisation | Genomics England |
Country | United Kingdom |
Sector | Public |
PI Contribution | Genomics England 100,000 genomes project: population diversity project Over the next 3 years GEL will sequence 20,000 patients from diverse populations. Neurology will be a major component of this and will benefit diagnosis and gene discovery in diverse, underrepresented populations in many ares of neurology |
Collaborator Contribution | Over the next 3 years GEL will sequence 20,000 patients from diverse populations. Neurology will be a major component of this and will benefit diagnosis and gene discovery in diverse, underrepresented populations in many ares of neurology |
Impact | None as yet |
Start Year | 2023 |
Description | Genomics England 100,000 genomes project Transcriptome sequencing |
Organisation | Genomics England |
Country | United Kingdom |
Sector | Public |
PI Contribution | Genomics England Transcriptome sequencing In 100,000 genomes project, patients that gave mRNA as PAXgene blood will have RNA extracted and transcriptome sequencing. We plan to investigate the transcriptome in comparison with the genome sequencing to increase diagnostic yield, indentify known and new disease gene pathways |
Collaborator Contribution | Genomics England Transcriptome sequencing In 100,000 genomes project, patients that gave mRNA as PAXgene blood will have RNA extracted and transcriptome sequencing. We plan to investigate the transcriptome in comparison with the genome sequencing to increase diagnostic yield, indentify known and new disease gene pathways. The transcriptome sequencing will benefit a number of rare disease projects |
Impact | None as yet |
Start Year | 2023 |
Description | Genomics England Genome Sequencing (100,000 genomes) and Neurology GeCIP (HH is co-lead) |
Organisation | Genomics England |
Country | United Kingdom |
Sector | Public |
PI Contribution | Genomics England Genome Sequencing (100,000 genomes) and Neurology GeCIP (HH is co-lead) |
Collaborator Contribution | Genomics England Genome Sequencing (100,000 genomes) and Neurology GeCIP (HH is co-lead) |
Impact | Genomics England Genome Sequencing (100,000 genomes) and Neurology GeCIP (HH is co-lead) |
Start Year | 2015 |
Description | Genomics England collaboration on new disease genes and risk factors |
Organisation | Genomics England |
Country | United Kingdom |
Sector | Public |
PI Contribution | Collaboration on disease genomes |
Collaborator Contribution | Collaboration on disease genomes |
Impact | See publications in high impact journals such as Nature Genetics |
Start Year | 2019 |
Description | Greek Collaboration on neurogenetics - Athens, Thessaloniki and Larisa |
Organisation | National and Kapodistrian University of Athens |
Department | Neurology Athens |
Country | Greece |
Sector | Academic/University |
PI Contribution | Greek Collaboration on neurogenetics - Athens, Thessaloniki and Larisa Sharing of DNA and clinical details on series and families |
Collaborator Contribution | Greek Collaboration on neurogenetics - Athens, Thessaloniki and Larisa Sharing of DNA and clinical details on series and families |
Impact | Sharing of families and data |
Start Year | 2011 |
Description | Laboratory of Neurogenetics, NIA |
Organisation | National Institutes of Health (NIH) |
Department | National Institute on Aging |
Country | United States |
Sector | Public |
PI Contribution | Collaborating on techniques such as developing DNA arrays and exome sequencing in our lab |
Collaborator Contribution | Collaboration on techniques and patients |
Impact | Joint publications and techniques |
Start Year | 2006 |
Description | Laboratory of Neurogenetics, NIA and NIH, USA |
Organisation | National Institutes of Health (NIH) |
Department | National Institute on Aging |
Country | United States |
Sector | Public |
PI Contribution | Data, cases, publications |
Collaborator Contribution | Sharing of data, cases and techniquesData and publications |
Impact | Publications, assistance with grants |
Description | Laboratory of Neurogenetics, NIA and NIH, USA |
Organisation | National Institutes of Health (NIH) |
Department | National Institute on Aging |
Country | United States |
Sector | Public |
PI Contribution | Data, cases, publications |
Collaborator Contribution | Sharing of data, cases and techniquesData and publications |
Impact | Publications, assistance with grants |
Description | Larisa Greek parkinsonism study |
Organisation | University of Thessaly |
Department | Neurology Thessaly |
Country | Greece |
Sector | Academic/University |
PI Contribution | Larisa Greek parkinsonism study. Over 1200 Greek parkinsonian patients and controls collected and DNA extracted |
Impact | Over 1200 Greek parkinsonian patients and controls collected and DNA extracted. Work ongoing, GWAS underway |
Start Year | 2010 |
Description | MRC Centre for Neuromuscular Diseases |
Organisation | University College London |
Department | MRC Centre for Neuromuscular Diseases |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The MRC Centre for Neuromuscular Diseases is an MRC funded centre set up to investigate the causes and identify treatments for neuromuscular diseases. |
Collaborator Contribution | The MRC Centre for Neuromuscular Diseases is an MRC funded centre set up to investigate the causes and identify treatments for neuromuscular diseases. I am a member and collaborator in the The MRC Centre for Neuromuscular Diseases. |
Impact | The MRC Centre for Neuromuscular Diseases is an MRC funded centre set up to investigate the causes and identify treatments for neuromuscular diseases. I am a member and collaborator in the The MRC Centre for Neuromuscular Diseases. |
Start Year | 2006 |
Description | MRC NMC |
Organisation | University College London |
Department | MRC Centre for Neuromuscular Diseases |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | I am a member of the MRC Centre for Neuromuscular Diseases which has brought in very important collaborations between myself and Mike Hanna and Mary Reilly. We have generated considerable data, patient information and publications. |
Collaborator Contribution | I am a member of the MRC Centre for Neuromuscular Diseases which has brought in very important collaborations between myself and Mike Hanna and Mary Reilly. We have generated considerable data, patient information and publications. |
Impact | I am a member of the MRC Centre for Neuromuscular Diseases which has brought in very important collaborations between myself and Mike Hanna and Mary Reilly. We have generated considerable data, patient information and publications. |
Start Year | 2008 |
Description | MSA Trust |
Organisation | Sarah Matheson Trust for MSA |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Data, tours of the lab, newsletter information |
Collaborator Contribution | Patients, we write a research update in the newletter, many patients have given blood and donated their brain as a result of the research |
Impact | Publications, data, tours of the lab, newsletter information |
Start Year | 2006 |
Description | NORD |
Organisation | National Organization for Rare Disorders (NORD) |
Country | United States |
Sector | Charity/Non Profit |
PI Contribution | Patient's referred and a grant |
Collaborator Contribution | Patient's referred and a grant |
Impact | Patient's referred and a grant |
Start Year | 2008 |
Description | Neuromics FP7 collaboration |
Organisation | European Commission |
Department | Seventh Framework Programme (FP7) |
Country | European Union (EU) |
Sector | Public |
PI Contribution | Neuromics FP7 collaboration where we received funding for a post-doc (to prof hanna) and also funding for sequencing. There was significant collaboration and added value from this collaboration with shared results and materials |
Collaborator Contribution | Shared results and materials - genome/exome sequencing, functional data and patient materials |
Impact | Publications, collaboration and preparation for other rare disease grants |
Start Year | 2012 |
Description | PENN collaboration on Dog ataxia and neuropathy |
Organisation | University of Pennsylvania |
Department | School of Veterinary Medicine (UPenn) |
Country | United States |
Sector | Academic/University |
PI Contribution | PENN collaboration on Dog ataxia and neuropathy. We are working on the genetics of neuropathy and ataxia in dog models of human disease |
Collaborator Contribution | Provided tissue and clinical details |
Impact | Joint grant submitted to NIH |
Start Year | 2010 |
Description | Sakhalin Universitycollaboration |
Organisation | Sakhalin State University |
Country | Russian Federation |
Sector | Academic/University |
PI Contribution | Collaboration on patients with Neuropathy in Russia |
Impact | ongoing |
Start Year | 2010 |
Description | Sarah Matheson Trust for MSA |
Organisation | Sarah Matheson Trust for MSA |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Brought patients and encouraged brain donation of MSA patients for our research |
Collaborator Contribution | Brought patients and encouraged brain donation of MSA patients for our research |
Impact | Publications, Brought patients and encouraged brain donation of MSA patients for our research |
Start Year | 2006 |
Description | Synaptopathies consortium |
Organisation | Partnership for Advanced Computing in Europe (PRACE) |
Country | Belgium |
Sector | Academic/University |
PI Contribution | Synaptopathies consortium: Wellcome Trust strategic award Sequencing in paroxysmal disorders with collaboration with Rothman, Kullmann, Hanna, Sisodiya, Goadsy and others |
Collaborator Contribution | Families and samples |
Impact | Built up a significant cohort |
Start Year | 2015 |
Description | University of Tehran |
Organisation | University of Tehran |
Country | Iran, Islamic Republic of |
Sector | Academic/University |
PI Contribution | Prof Elahe has provided many inportant families for our research and we currently share a PhD student |
Collaborator Contribution | Prof Elahe has provided many inportant families for our research and we currently share a PhD student |
Impact | Prof Elahe has provided many inportant families for our research and we currently share a PhD student |
Start Year | 2009 |
Description | Wayne State University |
Organisation | Wayne State University |
Country | United States |
Sector | Academic/University |
PI Contribution | Sharing of CMT1A patient data and DNA |
Collaborator Contribution | Sharing of CMT1A patient data and DNA |
Impact | Sharing of CMT1A patient data and DNA |
Start Year | 2008 |
Description | "Genomics in Neurodegenerative disease -- what are we up to" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited Lecture as HKUST IAS fellow, Hong Kong |
Year(s) Of Engagement Activity | 2019 |
Description | "Neurogenetic Foundations of Movement Disorders - The Key to Cure?" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited Keynote Lecture |
Year(s) Of Engagement Activity | 2019 |
Description | "The Genetics of the Dementias" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Invited teaching lecture at Queen Square on MSc Human Genetics course 2018-19 |
Year(s) Of Engagement Activity | 2019 |
Description | Advances in Alzheimer's Disease |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker - The 10th Xiangya International Symposium of the Clinical and Basic Research on Neurodegenerative Disorders, China |
Year(s) Of Engagement Activity | 2019 |
Description | Alzheimer's disease pathogenesis: what do we know and why have clinical trials failed |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Invited public lecture |
Year(s) Of Engagement Activity | 2019 |
Description | Aß hypothesis, AD genetics" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited lecture - Wenner-Gren Center (Sveavägen 166), Stockholm, Sweden symposium : "Amyloid diseases: from biochemistry to clinical applications" |
Year(s) Of Engagement Activity | 2019 |
Description | Crispr Talk - John and Selina |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Invited Lecture Royal London Hospital |
Year(s) Of Engagement Activity | 2019 |
Description | Epidemiology of Alzheimer's Disease and Related Disorders |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited Keynote speaker on teaching course at Bordeaux School of Neuroscience |
Year(s) Of Engagement Activity | 2019 |
Description | Genetic analysis of late onset degenerative diseases implicates failures of damage response |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Speaker invitation and Announcement of The Brain Prize Awardee 2019 Copenhagen, Denmark |
Year(s) Of Engagement Activity | 2019 |
Description | Genetics |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Supporters |
Results and Impact | Invited Lecture Weston's meeting - 50th Year Anniversary Symposium, 33 Queen Square |
Year(s) Of Engagement Activity | 2019 |
Description | Genetics |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Invited Lecture - Wolfson Institute for Biomedical Research (WIBR) mini-symposium - Sainsbury Wellcome Centre London |
Year(s) Of Engagement Activity | 2019 |
Description | Genetics |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Supporters |
Results and Impact | Wolfson final symposium - Institute of Child Health London |
Year(s) Of Engagement Activity | 2019 |
Description | Genetics in neurodegenerative disease |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited lecture at 2019 International Conference of Korean Dementia Association, (IC-KDA 2019) Seoul |
Year(s) Of Engagement Activity | 2019 |
Description | Genetics in neurodegenerative diseases |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Invited teaching to PhD students on Biomarkers for neurodegenerative diseases PhD course |
Year(s) Of Engagement Activity | 2019 |
Description | Genetics of Alzheimer's |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited lecture at Hong Kong University of Science and Technology ShenZhen branch |
Year(s) Of Engagement Activity | 2019 |
Description | Genetics of Alzheimer's and other neuro-degenerative disease |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited Lecture - China National Genebank - Jinsha Road, Dapeng New District, Shenzhen |
Year(s) Of Engagement Activity | 2019 |
Description | Genetics of Dementias |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited Lecture XXIV World Congress of Neurology, Dubai - AE |
Year(s) Of Engagement Activity | 2019 |
Description | Genetics of Neurodegeneration |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited Lecture at Lisbon AD/PD meeting |
Year(s) Of Engagement Activity | 2019 |
Description | Genomic analysis of neurodegenerative diseases |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Invited lecture Scientific Talk (to senior scientists) Odense University Hospital, Denmark |
Year(s) Of Engagement Activity | 2019 |
Description | Genomic analysis of the mechanisms of neurodegenerative disease in Denmark to PhD students |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Teaching Lecture to PhD students in neuroscience at the NeuroGrad Winter School, Copenhagen |
Year(s) Of Engagement Activity | 2019 |
URL | https://neurograd.ku.dk/neurograd-winter-school/ |
Description | Genomic clues to neurodegenerative disease mechanisms |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Brain Prize Special Lecture/ keynote lecture at ECNP Congress in Copenhagen |
Year(s) Of Engagement Activity | 2019 |
Description | Genomics England Genome Sequencing (100,000 genomes) and Neurology GeCIP (HH is co-lead) |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Genomics England Genome Sequencing (100,000 genomes) and Neurology GeCIP (HH is co-lead) |
Year(s) Of Engagement Activity | 2015,2017,2018,2019,2020 |
URL | http://www.genomicsengland.co.uk |
Description | Genomics of Neurodegeneration |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited lecture - 3rd Rijeka Forum on Neurodegenerative diseases, Croatia Rijeka |
Year(s) Of Engagement Activity | 2019 |
Description | Genomics of neurodegenerative disease |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Keynote speaker FENS The Serbian Neuroscience Society. with the Neuroscience societies of Romania and Turkey. Belgrade Serbia. |
Year(s) Of Engagement Activity | 2019 |
Description | Grand Rounds Invitation: Albert Einstein College of Medicine - Montefiore Medical Center |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Grand Rounds Invitation: Albert Einstein College of Medicine - Montefiore Medical Center talk entitled: Genomic analysis of neurodegenerative diseases implicates failures of damage clearance with Q&A |
Year(s) Of Engagement Activity | 2021 |
Description | HSP society |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | HSP yearly meet and section in HSP booklet |
Year(s) Of Engagement Activity | 2012,2013 |
Description | Inaugural Baillieu Myer Lecture |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Inaugural Baillieu Myer Lecture, in honour of contribution to medical research, in particular dementia research |
Year(s) Of Engagement Activity | 2019 |
Description | Invited Round table public talk |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Invited public round table - Brain Prize Evening - Lundbeck - BNA Festival, The Convention Centre Dublin |
Year(s) Of Engagement Activity | 2019 |
Description | Invited speaker NIH Clinical Neuroscience Grand Rounds Main Lecture Speaker |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speaker talk entitled: Genomic Analysis of the Major Neurodegenerative Diseases - NIH Clinical Neuroscience Grand Rounds with Q&A |
Year(s) Of Engagement Activity | 2021 |
Description | Invited talk to the Elderly |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Invited speaker at Chinese Dementia Meeting at Community Elder Center at Hebei, China |
Year(s) Of Engagement Activity | 2019 |
Description | Meet the Professors |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited Round table public talk |
Year(s) Of Engagement Activity | 2019 |
Description | Muscle Study group UK and international |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Genetics and exome sequencing in Muscle Disease Collaboration |
Year(s) Of Engagement Activity | 2013 |
Description | Neanderthals - talk for The National Trust |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Lecture in response to a request to talk to a regional National Trust membership |
Year(s) Of Engagement Activity | 2019 |
Description | Neuromuscular research day |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Around 100 patients More patients involved in our research |
Year(s) Of Engagement Activity | 2007,2008,2009,2010 |
Description | Opening lecture: Alzheimer's disease: a personal view on early diagnosis and treatment |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited Lecture - XVIII Teófilo Hernando's International Summer School of Pharmacology Frontier Biomarkers and Drug Discovery for the Early Diagnosis and Treatment of Alzheimer's Disease |
Year(s) Of Engagement Activity | 2019 |
Description | Progress in the genomic analysis of neurodegeneration |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Lecture to the department of Neurodegenerative Disease as an update on work in progress |
Year(s) Of Engagement Activity | 2019 |
Description | Rethinking PD: From a Single Disease to Multiple Diseases:: Genetics, Epigenetics and Environmental Factors |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited Lecture by The Preuss Foundation Seminar on State of the Art Parkinson's Disease Research ~ La Jolla, California |
Year(s) Of Engagement Activity | 2019 |
Description | Session 4 - Panel discussion: 'The Future of Neuroscience' |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Invited Lecture - UCL Neuroscience Symposium 10th Anniversary, UCL Institute of Education |
Year(s) Of Engagement Activity | 2019 |
Description | Skype 2 hour lecture to students |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited Teaching Lecture to Masters Students "Athens International Master's Programme in Neurosciences" University of Athens Department of Biology |
Year(s) Of Engagement Activity | 2019 |
Description | The importance of genetics and molecular biology in neurodegenerative diseases |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Invitation to Lecture on MRes Translational Neuroscience programme - 7 Queen Square |
Year(s) Of Engagement Activity | 2019 |
Description | The importance of genetics and molecular biology in neurodegenerative diseases |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Invited teaching UCL - Basic neuroscience and investigation of Nervous system - CLNE0009 Queen Square |
Year(s) Of Engagement Activity | 2019 |
Description | The role of genetics and genetic testing in PD |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited Lecture at World Parkinson Coalition 2019 Kyoto, Japan |
Year(s) Of Engagement Activity | 2019 |
Description | invited speaker 12th European Congress of Neuropathology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited Lecture entitled: Clues to the aetiology of neurodegenerative diseases from genomic analysis at 12th European Congress of Neuropathology |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.ecnp2020.dk/ |
Description | talk on Genetics at McGill University in Canada |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Invited Lecture |
Year(s) Of Engagement Activity | 2019 |