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Gene sequencing shapes the future of veterinary science
RCVS Charitable Trust conference: ‘Next generation sequencing – the role of new sequence technologies in shaping the future of veterinary science’
On 26 June 2012, vets from academia and in practice met with leading experts in gene sequencing, policy makers and animal charities to discuss the latest developments in the technologies involved. These innovations were largely driven by demand in human medicine but are becoming more widely and cheaply available in veterinary medicine – which has real implications for veterinary surgeons whether in academia or in practice. A better understanding of genomes such as those involved in the production of methane, a greenhouse gas, by ruminants could also potentially have a positive impact for the environment.
The conference was also intended to disseminate more widely some outcomes of the RCVS Charitable Trust Golden Jubilee project to decode the sequences of 50 pathogenic genomes – one for each of the 50 years of the Trust. This research was led by Dr Alan Radford, senior lecturer in the Department of Infection Biology at the University of Liverpool, with £250,000 granted by the Trust. The genomes sequenced were selected after asking universities and institutes to apply to have one or more pathogens sequenced in conjunction with experts at Liverpool. This increased collaborations between veterinary surgeons in clinics and in research institutions around the UK, and offered scope for all those working in animal infection to gain high quality research experience.
The project concluded in July 2011. Several research publications have been produced including the very high profile Analysis of Gene Expression from the Wolbachia Genome of a Filarial Nematode Supports Both Metabolic and Defensive Roles within the Symbiosis in Genome Research. Available: http://genome.cshlp.org/content/early/2012/08/16/gr.138420.112.full.pdf+html (Last accessed 30th August 2012. Available online for free.) This paper sums up the project. Dr Ben Makepeace, who led the work, calls the Trust sponsored genome the foundation of the paper, on which the rest was built. Further publications are in progress.
Four genomes sequenced under the auspices of this research were also featured amongst the presentations at this conference.
Dr Alan Radford’s summary of the Vetseq project presentation (PDF 935Kb).
A selection of literature searches relating to this conference (PDF 589Kb).
Other presentations at the symposium
Current ‘next generation’ sequencing methodologies and what they can do - Professor Neil Hall
Sequencing animal genomes, including lessons from human medicine - Professor Alan Archibald
Sequencing pathogens: from large to small, from virulent to benign - Dr Ian Goodhead
Discovering new pathogens - Dr Alan Radford
Golden Jubilee genome: whole genome sequencing of haemoplasmas – shedding new light on old pathogens - Dr Emi Barker
Golden Jubilee genome: Wolbachia gene expression and river blindness – a sinuous tale from comparative medicine - Dr Ben Makepeace
Sequencing the rumen microbial population (the microbiome) - opportunities for biotech and the environment - Dr Mick Watson
Problems and pitfalls: closing genomes, informatics, and errors - Dr Ian Goodhead
The current state of UK next-generation resources and challenges for the future - Professor Neil Hall
Professor Neil Hall, Co-Director of the Centre for Genomics Research, University of Liverpool, outlined how rapidly sequencing technology is changing and bringing the ‘impossible’ into reach. Bottlenecks no longer exist in the time taken to determine the base pairs of a genome, as these can now be determined at the rate of around 100 million each day – compared with 1,000 a day ten years ago. This has correspondingly reduced genome sequencing costs. The challenges in sequencing now involve obtaining high quality samples, and the analysis of results.
Professor Neil Hall’s presentation (PDF 1.9Mb). Presentation video (to follow shortly).
An outline of veterinary work that has been done so far to sequence genomes was presented by Professor Alan Archibald, Head of the Division of Genetics and Genomics, Roslin Institute. This has particularly focused on production animals such as sheep and pigs, endangered animals such as the panda, and pets. He emphasised how sharing research techniques and results with human medicine can increase the quality of the results in both fields. Similarly, there are pathogens, such as bovine TB, of interest to human and veterinary medicine. The next steps needed are to make sure that veterinary and human medicinal scientists can become more efficient through greater sharing and dissemination of their work.
A case study demonstrating this link between veterinary and human pathogens was introduced by Dr Ian Goodhead of the Centre for Genomics Research, University of Liverpool. Different types of the Trypanosoma brucei parasite are found in humans and in cows across Africa. In humans, two strains of the parasite cause ‘sleeping sickness’, which is fatal, if untreated. The Trypanosoma brucei parasite affecting cattle increases their susceptibility to other infections, and costs more than $1bn a year in lost livestock and crop production. Genome sequencing helped find that resistance to the cattle parasite could be inherited and this is now being researched further, with implications for tackling both the human and cattle disease.
Dr Ian Goodhead’s presentation (PDF 2.4Mb).
Dr Alan Radford next showed how gene sequencing can quickly identify new pathogens, including those which have not previously been found in a particular species. He highlighted the cases of two new pathogens identified and sequenced in recent years; the coronavirus responsible for severe acute respiratory syndrome (SARS), which required a global collaboration using older technologies to sequence, and the Schmallenberg Virus, where these new technologies allowed for its quick identification as an orthobunyavirus at the Friedrich Loeffler Institute in Germany, the research institution that led the collaborative European-wide investigations.
Dr Alan Radford’s presentation (PDF 1.4Mb).
Golden Jubilee genome: whole genome sequencing of haemoplasmas – shedding new light on old pathogens
The bacteria responsible for Feline haemoplasmosis, a common infectious disease in cats, was sequenced at the request of Dr Emi Barker at the University of Bristol, who took part in the research as a PhD student at Bristol supervised by Dr Séverine Tasker. Emi explained how this genome sequence has offered insights into what is an uncultivable haemoplasma, which, since it lacks some of the metabolic pathways found in cultivable mycoplasmas, is considered a fastidious bacteria. This research also detailed a potential mechanism by which feline haemoplasmas invade their host’s immune system.
Photo: Dr Severine Tasker (left) and Dr Emi Barker (right)
Dr Emi Barker’s presentation (PDF 1.5Mb).
Dr Andrew Waller, Head of Bacteriology at the Animal Health Trust, presented findings deriving from sequencing the bacteria Streptoccus equi subsp. zooepidemicus, which in 2010 affected almost the entire equine population of Iceland. Sequencing revealed four branches in this pathogen’s genome, and showed that a vaccination would need to provide broad coverage of strains. It also allowed mapping the spread of the disease, tracing it back to its first location in Iceland – where poor hygiene practices could be found and linked to its transmission.
Dr Andrew Waller’s presentation (pdf 2.4Mb). A selection of literature searches relating to this conference (PDF 220Kb). Accompanying video (to follow shortly).
Progress on sequencing African swine fever virus was presented by Dr Chris Netherton, senior postdoctoral scientist at the Institute of Animal Health. African swine fever is an important notifiable infection which is endemic in many African countries and in Sardinia. In 2007, it was introduced to Georgia, Armenia, Azerbaijan and Russia, where, by 2011, it had spread to 16 states. The sequencing of this genome is providing information useful to studies on gene function, vaccine development and for monitoring genome evolution.
Golden Jubilee genome: Wolbachia gene expression and River Blindness – a sinuous tale from comparative medicine
The final presentation on a genome sequenced under the 50 Genomes project was given by Dr Ben Makepeace of the University of Liverpool. This was the Wolbachia bacteria, which, in 2006, was discovered by former RCVS President Professor Lord Trees and colleagues to be vital to the Onchocerca volvulus worm that causes River Blindness, a disease affecting 37 million people in sub-Saharan Africa.
Its closest relative, the Onchocerca ochengi worm, causes disease in cattle. By sequencing the Wolbachia genome it has been possible to confirm that the bacteria provide metabolic and immune defence functions in these Onchocerca worms, and give valuable information about how this occurs.
Dr Ben Makepeace’s presentation (PDF 3.8Kb).
Sequencing the rumen microbial population (the microbiome) - opportunities for biotech and the environment
Dr Mick Watson presented work undertaken at the Roslin Institute, University of Edinburgh, and Ark-Genomics, which takes a different standpoint to studies looking at individual genomes. This research considers an individual as a ‘super-organism,’ a composite of host and microbial cells contributing to that individual’s survival. At present this is looking at the ‘genetic landscape’ of cow and sheep rumens in the hope of finding a means of reducing methane, a greenhouse gas that is emitted by ruminants.
As ruminant livestock already account for about 28% of methane emissions from human-related activities globally, and demands for food are predicted to rise enormously over the next 50 years, reducing these emissions seems increasingly important.
Dr Mick Watson’s presentation (PDF 838Kb). Presentation video (to follow).
Dr Ian Goodhead discussed some of the basic concepts in genome sequencing and assembly, and the choices scientists need to make. For example, there may exist already a sequenced genome against which a genome’s sequence can be referenced – an alignment approach – but if not, a new sequence may need to be assembled. He stressed the need to make these choices at the beginning of designing experiments – and that help is available from sequencing laboratories.
Dr Ian Goodhead’s presentation (PDF 1.6Mb).
The concluding presentation was given by Professor Neil Hall, who looked at the current state of the UKs next-generation resources and the challenges for the future. The present technology is moving out from specialist laboratories, and new, third-generation technologies able to process even single molecules are starting to be produced. These machines are getting ever smaller, cheaper and simpler to use – making it conceivable that they could become ‘standard kit’ in veterinary practices.
Professor Neil Hall’s presentation (PDF 2.3Mb).