High throughput Sequencing Hub for the North of England
Lead Research Organisation:
University of Liverpool
Department Name: Sch of Biological Sciences
Abstract
DNA sequence has always been an important source of inspiration for advances in medical and clinical research. This culminated in the sequencing of the first human genome, a project that took 6-8 years and several billion pounds. As a result we were able to discover the number and identity of genes that defined the human form though it is taking much longer to work out how these genes interact. But we know that people vary from each other in their disease susceptibility or in the way that they respond to treatment. The current need is to understand the basis of this variation and to use it to understand more fully how to define the most appropriate treatment to particular patients presenting with a particular condition. This is called ?personalised medicine? and it is widely thought to be the best way of optimising treatment.
Achieving this requires establishing the DNA sequence of particular genes in those patients, and this requires much more productive sequencing technologies. Fortunately, new instruments are now becoming available which can sequence a human in just a few weeks for approx #10-50,000. The Advanced Genomics Facility (AGF), located in Liverpool, is a leading UK centre of excellence and service provider for the new generation of sequencing technologies. We want to expand the capacity of the AGF to serve the research leaders in Universities and hospitals of the North of England by offering a one-stop shop that provides advice for all stages of the work. We shall also provide training and pump-prime cost-sharing programmes helping client groups to turn DNA sequence into knowledge.
Achieving this requires establishing the DNA sequence of particular genes in those patients, and this requires much more productive sequencing technologies. Fortunately, new instruments are now becoming available which can sequence a human in just a few weeks for approx #10-50,000. The Advanced Genomics Facility (AGF), located in Liverpool, is a leading UK centre of excellence and service provider for the new generation of sequencing technologies. We want to expand the capacity of the AGF to serve the research leaders in Universities and hospitals of the North of England by offering a one-stop shop that provides advice for all stages of the work. We shall also provide training and pump-prime cost-sharing programmes helping client groups to turn DNA sequence into knowledge.
Technical Summary
The North of England has substantial amounts of class-leading medical and clinical research based in major Universities and NHS Trusts, all of which would benefit greatly from access to second generation (2G) DNA sequencing technology, particularly in meeting the challenges of tumour sequencing, genetic susceptibility and personalised medicine. The Advanced Genomics Facility (AGF), located in Liverpool, is a leading UK centre of excellence and service provider for nextgen sequencing. We propose to expand the capacity of the AGF to serve the MRC-related interests in the Universities and NHS Trusts in a consortium covering Liverpool (lead), Manchester, Sheffield, and Lancaster. We shall provide expert access to all three major second generation (2G) technologies, to informatic processing and analysis techniques, and in the medium-term to third generation (3G) technologies. We shall provide training and pump-prime cost-sharing programmes helping client groups to turn DNA sequence into knowledge. Important points in the favour of the AGF include: a strong track record of servicing academic clients; a leading edge position in genome science and sequencing technology; an experienced workforce; minimised consumables costs; multiple platforms; expert informatics capability; a mature open door policy on research collaboration; a training and translation strategy; close working relationships with 2G technology providers including discussions with a 3G provider; and excellent links into the regional and nextgen sequencing communities.
Publications
Goodhead I
(2010)
A comprehensive genetic analysis of candidate genes regulating response to Trypanosoma congolense infection in mice.
in PLoS neglected tropical diseases
Payton A
(2010)
Investigation of a functional quinine oxidoreductase (NQO2) polymorphism and cognitive decline.
in Neurobiology of aging
Vaysse A
(2011)
Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping.
in PLoS genetics
Quilez J
(2011)
A selective sweep of >8 Mb on chromosome 26 in the Boxer genome.
in BMC genomics
Fox-Clipsham LY
(2011)
Identification of a mutation associated with fatal Foal Immunodeficiency Syndrome in the Fell and Dales pony.
in PLoS genetics
Holliday KL
(2012)
The non-synonymous SNP, R1150W, in SCN9A is not associated with chronic widespread pain susceptibility.
in Molecular pain
Quilez J
(2012)
Genetic control of canine leishmaniasis: genome-wide association study and genomic selection analysis.
in PloS one
Alsaadi MM
(2012)
From a single whole exome read to notions of clinical screening: primary ciliary dyskinesia and RSPH9 p.Lys268del in the Arabian Peninsula.
in Annals of human genetics
Chinoy H
(2012)
Genetic association study of NF-?B genes in UK Caucasian adult and juvenile onset idiopathic inflammatory myopathy.
in Rheumatology (Oxford, England)
Luciano M
(2012)
Genome-wide association uncovers shared genetic effects among personality traits and mood states.
in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Vinkhuyzen AA
(2012)
Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion.
in Translational psychiatry
Scholey RA
(2012)
Investigating host genetic factors in bovine digital dermatitis.
in The Veterinary record
Brenchley R
(2012)
Analysis of the bread wheat genome using whole-genome shotgun sequencing.
in Nature
Lopez LM
(2012)
Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts.
in European journal of human genetics : EJHG
Harris JR
(2012)
Toward a roadmap in global biobanking for health.
in European journal of human genetics : EJHG
Hamilton G
(2012)
The role of ECE1 variants in cognitive ability in old age and Alzheimer's disease risk.
in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Chinoy H
(2012)
Interaction of HLA-DRB1*03 and smoking for the development of anti-Jo-1 antibodies in adult idiopathic inflammatory myopathies: a European-wide case study.
in Annals of the rheumatic diseases
ArcOGEN Consortium
(2012)
Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study.
in Lancet (London, England)
Hudson G
(2013)
No evidence of an association between mitochondrial DNA variants and osteoarthritis in 7393 cases and 5122 controls.
in Annals of the rheumatic diseases
Elliott KS
(2013)
Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data.
in Annals of the rheumatic diseases
Peters MJ
(2013)
Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region.
in Annals of the rheumatic diseases
Miller FW
(2013)
Genome-wide association study of dermatomyositis reveals genetic overlap with other autoimmune disorders.
in Arthritis and rheumatism
Narayanan RP
(2013)
IGF2 gene polymorphisms and IGF-II concentration are determinants of longitudinal weight trends in type 2 diabetes.
in Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
Baird AE
(2014)
Genome-wide association study identifies genomic regions of association for cruciate ligament rupture in Newfoundland dogs.
in Animal genetics
| Description | BBSRC responsive mode |
| Amount | £433,798 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2011 |
| End | 03/2013 |
| Title | DNA sequence data |
| Description | Every week we generate >10gb DNA sequence from range of samples provided by collaborating groups. This can be from human/plants/microbes or animals. |
| Type Of Material | Database/Collection of Data/Biological Samples |
| Year Produced | 2006 |
| Provided To Others? | Yes |
| Impact | Our data has been used to develop new tools such as Pyronoyes (Quince et al) and RY mapper (Ashelford et al). It has fed into databases such as EUPAthDB. |
| Description | Collaborations with Unilever |
| Organisation | Unilever |
| Department | Unilever UK R&D Centre Port Sunlight |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Genome data generation to underpin programs in personal and home care divisions of Unilever. |
| Collaborator Contribution | Provision of materials. |
| Impact | Better understanding within Unilever of microbial communities as relevant to personal and home care. |
| Start Year | 2013 |
| Description | NHS PhD fellowship Julie Sibbering |
| Organisation | Liverpool Womens NHS Foundation Trust |
| Department | Liverpool Women's Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | We are hosting an NHS research Fellow. Julie Sibbering was working in the clinical diagnostics lab at the liverpool womens hostpital and was awarded the fellowship to work in my lab of Next-gen sequencing methods to identify chromosome abnormalities. |
| Collaborator Contribution | Julie Sibbering brings expertise in clinical diagnostics to the group. |
| Impact | Funding from NHS for fellowship. Training for the student. |
| Start Year | 2009 |
| Description | PHE HPRU |
| Organisation | Public Health England |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | The CGR is a key part of the sequencing capability for Public Health Protection research unit. Part of the CGR |
| Collaborator Contribution | They have provided samples and expertise which have allowed our group to be part of publications and to develop piplines and analyses for other projects. |
| Impact | Several papers on the analysis of west african ebola |
| Start Year | 2014 |
| Description | School teacher training |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Primary Audience | Schools |
| Results and Impact | A group of teachers from a local school came for CPD training in modern biological techniques. They received presentation and hands on experience using genomic technology The school reported this was the best CPD they ever had. |
| Year(s) Of Engagement Activity | 2010 |