Strangles, caused by Streptococcus equi remains the most frequently identified infectious disease of horses around the World, with the notable exception of Iceland. Over 600 outbreaks of strangles occur in the UK each year leading to significant disruption of equine events and cost to an industry worth over £7 billion per annum to the UK economy. All infected horses may suffer clinical signs of disease during the course of an outbreak, with approximately 2% requiring euthanasia. Approximately 10% of recovered horses become persistently infected. The exposure of naïve horses to Streptococcus equi that is shed from healthy carrier animals during participation in equestrian events or sales is difficult, if not impossible, to avoid. Therefore, the availability of a safe and effective vaccine that protects horses from developing strangles despite their being exposed to Streptococcus equi would have far-reaching benefits for equine welfare and equestrian activities throughout the World. However, the only available strangles vaccine in Europe, a live bacterial vaccine known as Equilis StrepE, provides protection to horses for only a short period of time (3 months). We have modified a recently identified superantigen, named SzeQ, which normally misdirects the immune response, so that it can instead be used to strengthen the immune response to vaccination. In this project we propose to fuse the modified SzeQ to proteins from Streptococcus equi, which can either be used directly, or be employed as a sticky coat on the surface of a prototype strangles vaccine. This coat will act as a type of 'Velcro', which attaches to immune cells, improving the strength and duration of the immune response. We will first produce and purify the Velcro protein in the laboratory and measure its activity and ability to induce a long-lasting immune response in ponies. Then we will attach it to the surface of a control strain of Streptococcus equi and measure its ability to stick to immune cells. Finally, we will produce the Velcro protein on the surface of a prototype strangles vaccine and determine if it improves the strength and duration of the immune responses produced following the vaccination of ponies and the ability of these responses to kill Streptococcus equi in the laboratory. This project has the potential to solve a significant problem in the development of safe and effective vaccines that protect against this highly prevalent and important disease of horses. Furthermore, coupling of the Velcro protein, or versions thereof, could also enhance the effectiveness of an array of other vaccines to protect pigs, cattle, sheep and man.

Media interest has brought health-related problems in purebred dogs to the public's attention, resulting in several ongoing enquiries sponsored by the government and independent organizations. Although we do not yet know the outcome of all of these reviews, they are likely to highlight many of the same issues as those identified by the RSPCA in their recent report (2008). These include problems resulting from excessive inbreeding and from inadvertent selection for disease traits in the course of selection for other characteristics (e.g. coat patterns). A prominent health issue in pedigree dogs, particularly large breeds, is that of hip dysplasia (HD), associated with painful and disabling osteoarthritis as the dog ages. There are currently attempts to reduce this disease in some breeds by preferentially breeding from dogs with low predisposition to disease. This involves selection using hip scores, x-ray measurements of hip laxity, which are associated with HD. However, the progress of genetic change by selection on hip scores has been found to be very slow. Furthermore, these tests involve putting the dog under general anaesthesia, which raises other animal welfare issues. Recent advances in canine genomics, including the sequencing of the dog genome and the development of a high-density 'chip' for dog genetic analysis, provide an opportunity for a faster and less invasive means to genetic improvement in these traits. This project applies a genomic approach to improving HD in dogs, using the Labrador Retriever breed as a test case. The Labrador is the most common dog breed in the UK and in many other countries, and one in which rates of HD and are relatively high. Our primary objective is to look for associations between the genetic constitution of dogs and their predisposition to HD and in so doing, we will identify regions of the genome that influence this trait. Using this information, we can provide 'genomic breeding values' for each dog analyzed, this value will encompass the dog's predisposition to HD, based on its genetic make-up. We will also further characterize the most promising genetic region associated with this disease by comparing our results to those of previous studies. We will then examine the relationship between hip dysplasia and other traits, including elbow dysplasia, a related disease, and specifically test whether the same regions of the genome are associated with predisposition to both diseases. Our second objective is to develop a plan for implementation of 'genomic selection' (selection based on many genetic markers) in Labradors. The costs of genetic testing are high and much of the variation that is measured in standard tests will not be related to these traits. We will use information from the analysis to evaluate whether a subset of genetic markers is predictive of disease susceptibility. If such a set can be identified, it may be possible develop a cost-effective means of testing for HD in the Labrador, which may also be applicable to other breeds. Using computer models and the results from the genetic analyses, we will evaluate how best to design a breeding and genotyping scheme for this and other diseases.

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