Genomic Selection for Bovine Tuberculosis Resistance

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Bovine tuberculosis (bTB) is a chronic respiratory disease caused by the pathogen, Mycobacterium bovis. Despite many years of statutory testing and slaughter, bTB still has major impacts on the health and welfare of UK cattle and the livestock economy. Substantial evidence now exists that the risk of a herd contracting this disease is variable and has a strong genetic component. We propose to build on our recent results from a genome wide association study (GWAS) in which we genotyped ca. 1200 cases and controls for 750,000 SNPs in the major UK dairy breed, the Holstein. We identified a marker-based heritability of 0.24 and chromosome wide significance for specific loci associated with bTB resistance. We now plan to provide accurate genomic predictors for bTB risk which can be directly applied by the dairy industry by combining our current data with additional datasets in a meta-analysis. We will exploit our unique biobank of DNA samples collected from bTB phenotyped cattle from high prevalence herds, to explore whether skin test positive, lesion negative animals have similar or distinct genotypes to our previous case definition of skin test positive, lesion positive animals. Further datasets available from collaborators consist of Holstein sires with estimated breeding values for bTB risk, and another case/control study. These have been genotyped at lower density compared to our samples. The meta-analysis of 5 distinct datasets will enable us to develop enhanced genomic predictors of bTB resistance calibrated by cross-validation, an essential requirement for GWAS studies. Predictors for complex traits in livestock based on whole genome sequencing are now on the horizon; we plan to whole genome sequence selected high and low bTB risk sires to provide novel information that could lead to further accuracy of the predictors as well as identifying novel SNPs closer to the causal loci, potentially identifying putative candidate genes for bTB resistance in cattle.

The goal of this proposed project is to help tackle the seemingly intractable problem of bovine tuberculosis (bTB) in the UK, caused by infection with the bacterium Mycobacterium bovis. This disease has shown a year on year increases in incidence, in cattle herds in both the UK and Republic of Ireland (ROI), especially over the last decade. We aim to take a novel approach to help combat the issue, by providing essential science-led information to the dairy industry, enabling it to utilise advanced genomic breeding tools for selecting for increased resistance to bTB. The major output from this project will be an enhancement of the health, welfare and productivity of UK cattle, adding to food security and contributing toward evidence based policy-making at a national and international level. This leads to both economic and societal impacts, as bTB is a costly and controversial problem for the UK government. It has major economic impacts on the UK livestock industry, especially as the UK does not enjoy bTB-free status, unlike the rest of the EU. Furthermore, the impact of bTB on the farmers dealing with this problem is immensely distressing, with many farms being under statutory restrictions on animal movement for considerable periods of time. Thus, any measures to lessen the disease impact will be beneficial at many levels. Our project will provide information and tools directly applicable to the dairy industry through DairyCo who are supportive and will facilitate the necessary technology transfer. The information provided will enable farmers to avoid using highly bTB susceptible sires and cows, and choose bulls which are expected by genomic prediction to be more bTB resistant. Uptake may be expected to be regional and dependent on individual circumstances, in that use by breeders may well be greatest in high bTB prevalence areas such as Northern Ireland, Wales and South West of England. Utilising accurate genomic predictors would be expected to also have a positive feed-back in that as ever-more resistant bulls are employed in a herd, the overall level of infection should be reduced, resulting in greater herd protection. Furthermore genomic selection for bTB resistance can be used as a complementary control measure alongside other strategies, and could have a positive benefit to other control efforts. Adoption of genomic predictors for bTB resistance would move towards providing a green and sustainable solution to the issue, and thus make major contributions to environmental sustainability, protection and impact reduction. Our proposal should also be seen as public-friendly as it should reduce the emphasis on badger controls and reduce the impacts of the hugely costly test and slaughter schemes. The project also has other benefits. It would have impact on the UK academic community by enhancing the knowledge economy, particularly for those engaged in animal health and agricultural/food production research. The project has potentially even greater benefit to the worldwide farming fraternity as our information will be invaluable in other countries where bTB is rife. It will provide information that could be applicable directly to Holstein-Friesian cattle herds globally, as well as potentially to other breeds of cattle. State-of-the-art technologies will be employed to tackle an important health trait and thus it will represent a proof-of-principle that could be applied to other infectious diseases of livestock. Furthermore, the project will provide training in the latest genomic technologies, and the PDRA employed on the project will become a highly skilled researcher. In summary, this is a proposed project with many direct and indirect benefits. The potential returns on investment for the research should be very high.