Genomic Selection for Bovine Tuberculosis Resistance
Lead Research Organisation:
Scotland's Rural College
Department Name: Research
Abstract
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Technical Summary
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.
Planned Impact
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.
Organisations
- Scotland's Rural College (Lead Research Organisation)
- Department For Environment, Food And Rural Affairs (DEFRA) (Collaboration)
- Government of Scotland (Collaboration)
- Department of Agriculture and Rural Development (DARDNI) (Collaboration)
- Teagasc (Collaboration)
- AGRI-FOOD AND BIOSCIENCES INSTITUTE (Collaboration)
- KING'S COLLEGE LONDON (Collaboration)
Publications
Banos G
(2017)
Genetic evaluation for bovine tuberculosis resistance in dairy cattle.
in Journal of dairy science
Glass EJ;
(2017)
Bovine TB and Host Genetics
Raphaka K
(2017)
Genomic regions underlying susceptibility to bovine tuberculosis in Holstein-Friesian cattle.
in BMC genetics
Wilkinson S
(2017)
Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows.
in BMC genomics
Wilkinson S
(2017)
A joint analysis of bovine tuberculosis resistance in dairy cattle.
Wilkinson S;
(2016)
Host genetics of resistance to bovine tuberculosis infection in dairy cattle
Description | We have found that breeding values using national data can be used to create deregressed proofs that can act as a phenotype for genomic breeding values. These gEBVs are readily accepted by the industry and have been received with high expectations. At subsequent KE events, farmers and industry influencers see the availability of TB Advantage as a great step forward in the control of TB. Furthermore, adding genotyped cows from TB affected herds adds to the accuracy of prediction. An award from CIEL to genotype a substantial number of cows (10,000) has added data to the reference population. |
Exploitation Route | The great thing about this project is its close proximity to industry through the connection with EGENES. All outputs that can be will be applied almost straight away due to the route to market through gEBVs and the involvement of EGENES in the project. Farmers can then select for increased TB resistance straight away - in fact that has been available to them since Jan 18th 2016 and this project is expected to improve the accuracy of predictions leading to even greater impact. |
Sectors | Agriculture Food and Drink Government Democracy and Justice |
URL | https://dairy.ahdb.org.uk/technical-information/breeding-genetics/tb-advantage/#.XGKvGzP7SUk |
Description | Outputs from the activity of the scientists involved in the project were discussed at a closed workshop organised by Professor Mike Coffey which included industry partners and government vets and others involved in TB research for Defra. Around 30 stakeholders from the research team, AHDB Dairy, BBSRC, HCC, Defra, APHA, Teagasc and DARDNI attended a 2 days closed workshop held in Cardiff to discuss the genetic and genomic improvement of TB resistance in UK dairy cattle. This led to government support to the release of gEBVs to industry in January 2016, funded and driven by AHDB Dairy delivered by EGENES from work conducted by SRUC and Roslin. This project provided some of the underlying confidence required by government to 'sanction' the release of gEBVs and furthermore to agree to continued supply of data. A follow up workshop was held in Belfast in November 2016 and Birmingham November 2017. A member of the project team (Professor Mike Coffey) was invited to a closed meeting with Michael Gove on the governments TB policy in January 2018 and in February 2018 the government announced a review of the 25 strategy on TB eradication to allow the inclusion of genetic selection for TB resistance. AHDB Dairy have won a significant award from Innovate UK (£360,000) to genotype 10,000 cows in the TB area and 2000 bulls with TB Advantage proofs to improve the accuracy of genomic predictions. EGENES now publishes TB Advantage genetic and genomic evaluations routinely 3 times per year for all dairy cattle and monthly for newly genotyped animals as an interim run. It continues to be very well received by industry. |
First Year Of Impact | 2017 |
Sector | Agriculture, Food and Drink,Government, Democracy and Justice |
Impact Types | Societal Economic |
Description | Input to the Godfray review committe on the Defra 25 year TB eradication strategy |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
Impact | The review was specifically targeted at new tests and genetics of resistance. Professor Mike Coffey attended a meeting at Defra which included around 20 heads of schools and departments involved in TB research and strategy definition plus Michael Gove. At that meeting the review was announced and we subsequently contributed 4 documents on genetics of TB resistance. We also had a teleconference with the committee to clarify some of the points made in our submission. The uptake of TB Advantage has been good by farmers and having the government review mention it a few times certainly increases its profile and enhances its impact. as with all genetic improvements, it will take time to measure the impact. |
URL | https://www.gov.uk/government/news/review-of-governments-bovine-tb-strategy-published |
Description | Dairy Co (now AHDB) grant for bovine tuberculosis genetic evaluations |
Amount | £100,000 (GBP) |
Organisation | Agricultural and Horticulture Development Board |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2014 |
End | 12/2015 |
Title | Integration of national TB testing data with cattle pedigree and performance data |
Description | Nationally collected TB testing results have been integrated into the national genetic evaluation systems for dairy cattle such that the genetics of TB resistance/tolerance in the national herd can be studied as part of the BBSRC Animal health Club research project |
Type Of Material | Improvements to research infrastructure |
Provided To Others? | No |
Impact | Given the system has been developed to integrate with national genetic evaluation systems when the research is completed it is likely to ease the implementation of results for the UK dairy industry - with relevant permissions. |
Title | Update of TB Advantage to include cow genotytpes in the reference population |
Description | AHDB were awarded ~£350,000 to genotype 10,000 cows and 1000 bulls in the TB affected area to add to the reference population for calculation of SNP effects. This also allows us to consider using the 1-step approach which provides greater prediction accuracy. |
Type Of Material | Improvements to research infrastructure |
Year Produced | 2019 |
Provided To Others? | No |
Impact | accuracy of prediction for TB resistance rises from about 40% to about 54% (depending on the information content for the animal). This has been considered by the EGENES technical advisory group (TAG) and will be rolled out to farmers later in 2019 after AHDB knowledge exchange officers have publicised it. |
Title | TB Project Genotyping Results |
Description | Raw SNP data and ancillary files from genome wide association studies on bovine tuberculosis BBSRC funded projects: CEDFAS initiative grants BB/E018386/1 and BB/E018335/1 and 2; Animal Health Research Club grant BB/L004054/1; Institute Strategic Programme Grants (ISP3 Innate Immunity & Endemic Disease) [BB/J004227/1], (ISP1 Analysis and Prediction in Complex Animal Systems) [BB/J004235/1] and (ISP2 Control of Infectious Diseases) [BB/P013740/1]. Abstract Holstein-Friesian raw SNP data. |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Dataset related to publication: 5. Wilkinson, S., Bishop, S.C. Allen, A.R., McBride, S.H., Skuce, R.A., Bermingham, M., Woolliams, J.A. and Glass, E.J. (2017) Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows. BMC Genomics, 18: 477. Dataset linked to Bermingham et al, 2014, Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis. Heredity, 112, 543-551. |
URL | https://www.research.ed.ac.uk/portal/en/datasets/liz-glass-tb-project-genotyping-results(7aa9bca3-a0... |
Description | Collaboration relating to genetics of bovine tuberculosis |
Organisation | Agri-Food and Biosciences Institute |
Country | United Kingdom |
Sector | Public |
PI Contribution | Secured two rounds of grant funding from BBSRC. Expertise in genome wide association studies. |
Collaborator Contribution | Epidemiology of bovine TB and data and samples from cases and controls to genotype and analyse. |
Impact | Multi-disciplinary: AFBI: epidemiology; bovine TB expertise; data analysis; surveillance Roslin: genetics; GWAS; genotyping; immunogenetics; innate immunity; host-pathogen interactions Outputs: See BB/E018335/1 and BB/E018335/2; BB/L004054/1; BB/L004119/1 Publications: Bermingham ML, Handel IG, Glass EJ, Woolliams JA, de Clare Bronsvoort BM, McBride SH..Bishop SC. (2015). Hui and Walter's latent-class model extended to estimate diagnostic test properties from surveillance data: a latent model for latent data. Scientific reports, pp. 11861 Bermingham ML, Bishop SC, Woolliams JA, Pong-Wong R, Allen AR, McBride SH..Glass EJ. (2014). Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis. Heredity, 112 (5), pp. 543-51 Tsairidou, S. Woolliams, J.A., Allen, A.R., Skuce, R.A., McBride, S.H., Wright, D.M., Bermingham, M.L., Pong-Wong, R., Matika, O., McDowell, S.W., Glass, E.J., Bishop, S.C. Genomic prediction for tuberculosis resistance in dairy cattle (2014) PLoS ONE, 9, e96728. doi:10.1371 Tsairidou S, Woolliams JA, Allen AR, Skuce RA, McBride SH, Wright DM..Bishop SC. (2014). Genomic prediction for tuberculosis resistance in dairy cattle. PloS one, 9 (5), pp. e96728 |
Start Year | 2006 |
Description | Data transfer from DARDNI (DEARA) |
Organisation | Department of Agriculture and Rural Development (DARDNI) |
Country | United Kingdom |
Sector | Public |
PI Contribution | We engaged with this department to agree file transfer formats and protocols for NI TB data pertinent to the calculation of TB Advantage EBVs. It is anticipated that these additional data will allow new bulls to get TB Advantage EBVs and will add to the accuracy of existing bulls with daughters in both GB and NI. Our team has been merging these animal records into the routine calculation of TB Advantage by EGENES |
Collaborator Contribution | The other partners (AFBI) were supportive of the process and assisted in shaping the proposition to DARDNI at the annual workshops |
Impact | The outcome is that we now have additional data from cows in NI that have bTB records. The data has been received, stored, validated, merged, cleaned, salvaged and the processes all automated by EGENES. The next steps expected over the new few months is to quantify the impact of additional data on TB Advantage and then release new EBVs. This will include higher accuracy EBVs for bulls with existing EBVs and EBVs for bulls with daughters only in NI. Subsequently, an assessment of the impact of additional data on the accuracy of genomic predictions will be made. |
Start Year | 2016 |
Description | UK and Ireland TB resistance workshop |
Organisation | Department For Environment, Food And Rural Affairs (DEFRA) |
Country | United Kingdom |
Sector | Public |
PI Contribution | We have produced breeding values (TB Advantage) that are now being used by the industry. The production of those gEBVs was through another project funded by AHDB Dairy but the outcomes have been used in this project to identify bulls for sequencing and for GWAS analyses. These gEBVs have been warmly received by industry and have been accepted by Defra as a useful addition to the toolbox for tackling TB |
Collaborator Contribution | Defra have agreed to fund APHA (internally) to provide continuous BCMS and TB data to allow us to continue producing gEBVs for the next 4 years at least. |
Impact | The outcomes are a closer relationship between the project and government on a genetic component to the national TB eradication plan |
Start Year | 2016 |
Description | UK and Ireland TB resistance workshop |
Organisation | Department of Agriculture and Rural Development (DARDNI) |
Country | United Kingdom |
Sector | Public |
PI Contribution | as before for Defra |
Collaborator Contribution | DARDNI keep records similar to BCMS and APHA. Currently, these data do not contribute to UK EBVs for TB resistance but following the workshop, we are now discussing how to get Northern Ireland data into the UK system of evaluations. |
Impact | None yet but it is expected to yield results in 2016. |
Start Year | 2016 |
Description | UK and Ireland TB resistance workshop |
Organisation | Government of Scotland |
Country | United Kingdom |
Sector | Public |
PI Contribution | We produce national genetic and genomic evaluations that rely on all UK data on cattle. Some of those animals originate in Scotland or end up in Scotland. Whilst there is no TB in Scotland, the availability of UK wide gEBVs for this trait provides selection options for Scottish Farmers |
Collaborator Contribution | TB evaluations rely on all UK data and Scottish data for CTS is held by BCMS. SG approval is needed to utilise these data and was given for continued use of the data for the purpose of national evaluations for TB resistance. |
Impact | The main outcome of SG involvement formally is that we now have approval for all devolved administrations for the use of national data in TB evaluations |
Start Year | 2016 |
Description | UK and Ireland TB resistance workshop |
Organisation | King's College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | as before for Defra |
Collaborator Contribution | as before for Defra |
Impact | HCC were one of the original funders to previous work that showed UK national data could be used for TB genetic evaluations (along with Defra). That work directly resulted in our ability to create the impacts we have through this project. |
Start Year | 2008 |
Description | UK and Ireland TB resistance workshop |
Organisation | Teagasc |
Department | Teagasc Food Research Centre |
Country | Ireland |
Sector | Academic/University |
PI Contribution | as for Defra but including the exchange of TB genetic evaluations for comparison with similar breeding values produced on Irish data. This creates sanity checking of results across country and provides confidence in use and outcomes. |
Collaborator Contribution | Teagasc contributed to the workshop by presenting results from Ireland and subsequently by exchanging genotypes with EGENES to add sires to the UK reference population for TB. |
Impact | A direct outcome is that the UK reference population increased by around 90 bulls (increase of about 5%) but these bulls were very informative. Increased interaction with Ireland on TB research has resulted. |
Start Year | 2015 |
Description | Bovine TB Resistance & Genetics Workshop; Belfast November 2016 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Following the success of the Workshop that the team ran in November 2015 in Cardiff, this was the second 2 day workshop on genetic improvement for bovine tuberculosis (bTB)resistance. The aim of the workshop was to discuss the genetics of bTB and breeding for bTB resistance between academic researchers, industry and government officials. attendees came from England, Northern Ireland and the Republic of Ireland and included representatitives from DEFRA, DAERA, AFBI, BBSRC and the Knowledge Transfer Network. The first day of the workshop discussed the current situation in England, Wales and Northern Ireland as well as Ireland; scientific advances in the genetics of bTB in dairy cattle as well as genetic evaluations for bTB resistance in UK and Ireland. The plan to sequence high and low risk sires for bTB resistance was presented. A new topic was discussed that of infectivity and the potential to combine selection for infectivity and susceptibility. The uptake of bTB resistance EBVs through AHDB as "TB Advantage" index was discussed. Future research priorities, including the potential impact of selection on economics and health and welfare of cattle in the dairy industry, potential for EBVs for bTB for beef breeds, interaction with other traits including Johne's disease and sharing of data were also discussed. The workshop further fostered dialogue between government officials, academics and industry on tackling bTB and was found to be useful and informative by all. |
Year(s) Of Engagement Activity | 2016 |
Description | Bovine TB Resistance & Genetics Workshop; Cardiff November 2015 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | The project team organised a 2 day workshop on bTB resistance held in 18-19 November 2015, Cardiff, UK. The aim of the workshop was to discuss the genetics of bTB and breeding for bTB resistance between not just academic researchers, but also importantly industry and government officials. Attendees included academics from United Kingdom, Northern Ireland and the Republic of Ireland and DEFRA, AFBI and representatives from the Welsh Government, BBSRC. The first day of the workshop involved a series of presentations from academics detailing the latest research results on the genetics of bTB resistance and officials describing the current situation on bTB prevalence across parts of the UK and ROI. The second day of the workshop started with presentations on the publications of EBVs for bTB resistance followed by a round-table discussion on bTB issues. Overall, it was shown that a genetic strategy to reduce bTB prevalence is a feasible option and this message was well received and supported. Concerns on the impact of breeding for bTB resistance on response to the tuberculin skin test were discussed. In addition, there were discussions on future directions of research on bTB genetics. The workshop fostered dialogue between government officials, academics and industry on tackling bTB and was found to be useful and informative by all. |
Year(s) Of Engagement Activity | 2015 |
Description | Magazine article |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | I wrote an article on selection for TB resistance for Country Life. |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.countrylife.co.uk/publication/country-life/country-life-march-18-2015 |
Description | New phenotypes for new traits |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Industry/Business |
Results and Impact | I presented a talk to farmers, vets, industry stakeholders, industry influencers at the AHDB DIG conference held at Nottingham on Feb 1/2. I included TB Advantage and the benefits to industry and society. |
Year(s) Of Engagement Activity | 2016 |
Description | Presentation at the Edinburgh Alliance for Complex Trait Genetics meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | The presentation took place on March 9, 2016, and focused on the new genetic and genomic evaluation system for bovine Tuberculosis. The event was attended by approx. 100 Edinburgh-based scientists and international visitors at the time. |
Year(s) Of Engagement Activity | 2016 |
Description | Radio interview |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | I was interviewed by Radio 4 Farming Today programme on the impending release of TB Advantage and the benefits of selection for TB resistance. |
Year(s) Of Engagement Activity | 2015 |
Description | TB Workshop |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Policymakers/politicians |
Results and Impact | Organised and attended the annual genetics of TB workshop held at SRUC HQ Edinburgh. Audience were drawn from GB, NI and Ireland. Defra CVO and other staff attended. Discussion was on control measures and deployment of novel tests. |
Year(s) Of Engagement Activity | 2019 |
Description | Visit to Defra |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Policymakers/politicians |
Results and Impact | I attended a meeting with a Defra official to update on a number of issues relating to the current grant and how to extend the reach of the project. We discussed a new proposal to AHDB to extend TB Advantage as applied in dairy cattle to beef. We also discussed a proposition we had previously made to Defra on how the results of this project might be greater through targeted genotyping of specific bulls and through more widespread genotyping of cows from herds with high prevalence of bTB. |
Year(s) Of Engagement Activity | 2017 |
Description | Wellcome Trust Board of Governors and Executive Board |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Supporters |
Results and Impact | The Wellcome Trust's Board of Governors and Executive Board visited Edinburgh University including the Roslin Institute on 19/20 September. The Post-doc on this grant, Samantha Wilkinson, Smaragda Tsairidou and Adrian Mwonge presented a joint poster on their work on various aspects of bovine TB host genetics, epidemiology and the detection test characteristics. |
Year(s) Of Engagement Activity | 2016 |
Description | visit to Defra |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | a workshop with Defra officials to inform on the results of the DairyCo project and how that fits into the BBSRC project of genomics of TB. As a result, we now have access to UK BCMS and TB data every 6 months and are in active dialogue with government officials on the use of national government data for research purposes and importantly for impact. |
Year(s) Of Engagement Activity | 2014 |