Variability, instability and pathology of the human genome

Lead Research Organisation: University of Leicester
Department Name: Genetics

Abstract

Significant advances in medicine and health care have been promised following the highly publicised release of the sequence of the human genetic material known as DNA. However, to fully exploit the opportunities heralded by access to this vast amount of information, a much greater understanding of the mechanisms that induce genetic alteration is required.
This proposal seeks to bring expertise in fundamental aspects of genetic variability together with clinical scientists concerned with investigating the impact of variation as a cause or contributor to human diseases. The objective is to maintain and expand a highly productive network at Leicester for the sharing of techniques, equipments and concepts unified by the study of the human genome. This Cooperative seeks to significantly enhance the speed of translation of fundamental discoveries of DNA variability and its inherent instability, into the development of novel strategies for targeted approaches to understanding the mechanisms leading to ill-health in humans.
The COGG is embedded within the Institute of Genetics at Leicester, which has invested in developing and maintaining a high quality website to illustrate and inform interested parties regarding the breadth of genetics-based activities and research ongoing at Leicester. Furthermore, individual COGG members will continue to speak regularly to a very broad range of public engagement in science events. The COGG will be further highlighted by the recent Queen?s Anniversary Award. The COGG members have strong links with educational establishments across the region and regularly provide talks and support seminars to sixth form students.

Technical Summary

The Leicester COGG in Human Genetics provides an integrated forum of research combining fundamental investigations relevant to human genome diversity and instability, together with environmental aspects of human mutation, through to the application of such studies to understanding the molecular genetic basis of human disease.
The present proposals will maintain the balance of the COGG between fundamental and medical genetics, whilst seeking to extend studies relevant to gene/environment interactions, to explore population-based genetic epidemiology of variation and to develop model systems to analyse the functional impact of DNA mutation.
Many of the studies embedded within the COGG have secured long-term support, adding significant value to the proposal to maintain and further develop this highly productive Cooperative.

Publications

10 25 50

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Samani NJ (2007) Genomewide association analysis of coronary artery disease. in The New England journal of medicine

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Stagno D'Alcontres M (2007) Lack of TRF2 in ALT cells causes PML-dependent p53 activation and loss of telomeric DNA. in The Journal of cell biology

 
Description BHF Project Grant
Amount £266,077 (GBP)
Organisation British Heart Foundation (BHF) 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2006 
End 09/2009
 
Description EU FP6
Amount £1,100,000 (GBP)
Organisation Sixth Framework Programme (FP6) 
Sector Public
Country European Union (EU)
Start 10/2006 
End 09/2008
 
Description EU FP7
Amount £186,174 (GBP)
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 10/2007 
End 09/2009
 
Description SRIF/University
Amount £2,500,000 (GBP)
Organisation Higher Education Funding Council for England 
Sector Public
Country United Kingdom
Start 10/2006 
End 09/2008
 
Description Wellcome Trust GWA call
Amount £629,434 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2007 
End 09/2010
 
Description Wellcome Trust Project Grant
Amount £251,226 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2006 
End 09/2009
 
Description CI-HHV-6 in sperm 
Organisation University of Leicester
Department Department of Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution The CI-HHV-6 research project was designed and initiated by me. The experimental work and data analysis were conducted by members of my research team and me. PMID: 24057213 The project is ongoing.
Collaborator Contribution Our collaborator in the Department of Genetics provided us with a panel of sperm DNA samples that we screened for CI-HHV-6 carriers. We were then able to obtain sufficient DNA for germline telomere length analysis from CI-HHV-6 donors. PMID: 24057213
Impact PMID: 24057213
 
Description WTCCC 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Two PIs in the Leicester COGG have been intimately involved with the Wellcome Trust Case-Control Consortium, with focus on developing new epidemiological and statistical tools and in exploring genes involved in heart disease.
Collaborator Contribution Provision of genome-wide SNP data.
Impact See PMID 17634449, 17554300
Start Year 2006
 
Description Award lectures 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact AJJ : 10 Award lectures to a diversity of scientific and lay audiences. NJS : 2 named award lectures to scientific audiences.

Significant media coverage.
Year(s) Of Engagement Activity 2006,2007,2008
 
Description Congress presentations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact AJJ: 11 congress presentations and keynote addresses. YED: 11 invited lectures and presentations. NJS: 15 invited lectures and presentations to national and international scientific meetings. NJR: 2 invited conference presentations. MAJ: 11 invited lectures and presentations to national and international meetings. PRB: 23 invited lectures and presentations to international/European meetings; 17 to meetings in UK.

Major exposure of COGG activities to wider scientific community. Lecture by NJS to the British Society of Human Genetics 2008 Meeting on "Genetic testing - ready for prime time" was featured on the Radio 4 Today programme and attracted wide media coverage. The paper by NJS on Genome-wide association analysis of coronary artery disease published in the NEJM was also widely featured in the national and international lay and scientific press and was considered one of the top 10 research papers in the cardiovascular field in 2007. The paper by the WTCCC published in Nature which included NJS and PB from the COGG was voted the best scientific paper of 2007 by several journal including Science, Lancet and Scientific American.
Year(s) Of Engagement Activity 2006,2007,2008
 
Description Desert Island Discs 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact AJJ was a guest on Radio 4's Desert Island Discs.

Major positive feedback from the public who seemed to enjoy the human face of science.
Year(s) Of Engagement Activity 2007
 
Description Industrial seminars 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact AJJ : 3 seminars to industrialists in pharmaceutical, nanotechnology and telecommunications fields.

Widening understanding of significance of molecular genetics within the broader technology community.
Year(s) Of Engagement Activity 2006,2007,2008
 
Description Institutional/departmental seminars 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact AJJ 10, MAJ 8, YED 5, NJS 5, PRB 5 institutional and departmental seminars to experts in the field.

Broadening awareness of COGG activities and stimulating collaborations.
Year(s) Of Engagement Activity 2006,2007,2008
 
Description Public lectures 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact AJJ 29 public lectures, YED 1 public lecture, NJS 2 public lectures, PRB 1 public lecture, MAJ 25 public lectures to a wide variety of audiences, including schoolchildren, lay public, police, lawyers etc. on broad topics of human genetics central to COGG activities. NJR's outreach activities with local primary and secondary schools included practical sessions with school science club and organising a half day visit of year 6 children to the Department of Genetics. All members contributed to an Open Day attracting 300 members of the public in 2005, involving lectures, practical demonstrations and posters.

Many of these presentations attracted significant press/media coverage. Also see congress presentations.
Year(s) Of Engagement Activity 2006,2007,2008