Using systems biology to understand and routinely predict health and welfare traits in dairy cattle

Lead Research Organisation: Moredun Research Institute
Department Name: Disease Control

Abstract

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Technical Summary

Using a systems biology approach we will explore the interactions that lead to and/or result in a poor health/welfare event in the dairy cow.

Assay. This project will routinely (bi-monthly for 2 years including a 6 month period of monthly sampling) assay the blood and milk of dairy cows for immunological parameters (natural antibodies, TNF-alpha, haptoglobin). These data will be collated with the routine collection of detailed data on MIR spectra (weekly) and other production (including product quality), health, welfare and fertility traits at the SAC Dairy Centre.

Integrate. Individual cow records collected on the farm include daily milk yield, live weight and body condition score, weekly milk fat and protein yield and milk somatic cell count, and thrice weekly feed and dry matter intake. Some of these data are routinely used as an indicator of welfare in farmed livestock (e.g., condition score). Also, these data will be collated in a SQL database to predict the ongoing body energy status of the dairy cow and therefore will be used to define the trajectory to negative body energy status (i.e., cow entering metabolic stress) and/or return to positive/neutral energy status. Health, welfare and fertility traits are also recorded under three main categories: (i) mastitis, (ii) reproductive problems (e.g., cystic ovaries, retained placenta, abortion), and (iii) lameness (e.g., sole ulcer, digital dermatitis, white line disease). Key fertility (e.g., calving interval, numbers of services) and reproductive (e.g., dystocia, stillbirth) parameters are also recorded.

Analyse. The data will be modelled to explore how temporal variation in the immunological parameters prior to welfare (including health) events could be used as early warnings of the subsequent event. Further, once sufficient samples are available, the milk MIR spectral data will be "trained" (SAC) to develop statistical predictions for the parameters that could be applied in routine milk recording.

Planned Impact

The future sustainability of the UK dairy industry relies on farmers being able to respond to key market signals and animal welfare is a key social (and economic) requirement. Key to addressing and responding to these signals is the ability to measure (or estimate), monitor and improve animal and production system attributes as they relate to animal welfare and other drivers (e.g., environment). This project offers a unique and innovative approach to preparing the UK dairy industry to address the challenges it will face to produce dairy products in a sustainable and socially acceptable manner. The partners have successfully worked together to begin to explore some of the key attributes of defining traits that relate to animal health and welfare and how these can be adopted by the industry. For example, SAC has delivered information on, and produced, practical dairy selection tools, particularly the inclusion of fertility, health, welfare and survival traits. These have helped UK dairy producers become more sustainable by adapting to a range of challenges, including consumer concerns; breeding for improved economic performance, animal health and welfare; and reduced environmental impact. Adoption of new indexes have improved animal health and welfare and economic performance compared to continued use of previous selection practices, and has cumulatively reduced greenhouse gas emissions per breeding animal by 1.4% (reduction in CO2 equivalents) per year in dairy systems. The overall annualised economic benefits of the genetic improvement that has taken place in the years 1980-2009 is worth £105.7 million/year to the UK dairy industry. A large proportion (~ 50%) has been realised by including health, fertility and longevity traits in UK dairy breeding goals.

As part of the project the partners will develop key knowledge transfer outputs, accessible to non-specialists. This will include developing display tools for participation in local public science events, including the Doors Open Days, Knowledge Scotland, Edinburgh Science Festival and Royal Highland Show. These will also be available to policy makers linking to Centres of Expertise in Scotland, in which the partners are involved. Given the inter-disciplinary nature of this project, the impacts of the proposed work will go beyond the direct academic beneficiaries, having positive economic and societal impacts across a range of stakeholders including:
1. Policy makers and dairy industry will be able to use the outcomes from this project to help summarise the manner by which the UK dairy industry are actively working towards improving the social acceptability (and sustainability) of the dairy production chain. Animal welfare is generally viewed as a public good, but will likely be undersupplied by producers for a variety of reasons including the lack of appropriate indicators of welfare status. The results of this project will provide signals for both producers and government (who might need to regulate animal welfare).
2. Animal managers may be able to use outputs from this work to direct early intervention for improved animal welfare as well as exploring the impact of key management interventions such as feeding and breeding. By combining systems of data collection that are already in place to develop predictive models of welfare events this project will allow us to work with the dairy industry to implement such early warning systems.
3. The public will benefit from this project through having access to data allowing them to assess the cow health/welfare impacts of the dairy products they consume.
4. The UK overall will benefit through the linkages between the research innovation represented in the partners and those delivering knowledge and tools to the industry (e.g., Veterinary Surveillance Services); the outcomes will result in a shorter period from primary research through to on-farm implementation helping UK agriculture reap the benefits of this project.
 
Description We have performed a large scale analysis of blood and milk samples from dairy cows which has identified some measures of the immune system which are both heritable and are associated with resistance to common diseases of cattle such as mastitis and infertility. We have also identified that the levels of number of important immune traits in milk vs. serum are highly correlated, meaning that serum levels of these traits can be quantified using less invasive milk sampling.
Finally we have demonstrated that levels of important immune markers in blood and milk can be estimated by detecting changes in the way the milk absorbs infrared light, meaining passive collection of immune trait data is possible through routinely recorded mid-infrared spectroscopy analysis of the milk.
Exploitation Route Heritable immune markers which are associated with increased resistance to disease could be used to select dairy cows which are more disease resistant. This would improve dairy cow welfare, improve the efficiency of milk production, and reduce the use of drugs such as antibiotics in the dairy industry.
The development of a simple method to record immune parameters in cattle via infrared absorption represents now means we can record immune function in large numbers of cattle on a repeated basis at minimal cost. Such immune measurements may be used to either select for 'good' immune traits which are associated with improved health, productivity and welfare, or as biomarkers for the early identification of disease.
Sectors Agriculture, Food and Drink,Environment

URL http://ac.els-cdn.com/S002203021730067X/1-s2.0-S002203021730067X-main.pdf?_tid=99112e4a-0977-11e7-8bc6-00000aacb361&acdnat=1489579673_fdf0c9ec90f602daee5ac15e61bad09c
 
Description The results from this project have been presented in industry meetings where dairy industry stakeholders have been made aware that immune biomarkers vary across animals and in relation to key health and welfare states of animals, and in many cases are under significant genetic control. This had particularly focused on the potential to use milk mid infrared (MRI) spectral analysis to predict key immune biomarkers within the farm. These MIR-based predictions can be used to identify health and welfare events on farm, or as traits for selective breeding programmes aimed at improving animal disease resistance.
First Year Of Impact 2015
Sector Agriculture, Food and Drink
 
Description AHDB studentship programme
Amount £685,777 (GBP)
Organisation Agricultural and Horticulture Development Board 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2014 
End 09/2017
 
Description KTN/BSAS Summer Vacation Scholarship Award
Amount £2,500 (GBP)
Organisation Knowledge Transfer Network 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2015 
End 08/2015
 
Description SRUC-MRI PhD studentship
Amount £75,000 (GBP)
Organisation Moredun Foundation funding 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 09/2019
 
Description The ecology within: The impact of gut ecosystem dynamics on host fitness in the wild
Amount £473,738 (GBP)
Funding ID NE/R01664X/1 
Organisation Natural Environment Research Council 
Sector Public
Country United Kingdom
Start 01/2019 
End 12/2023
 
Title High-throughput cell phenotyping of bovine leukocytes 
Description A method was developed to rapidly phenotype bovine blood leukocytes using high-throughput flow cytometry. The technique requires a small volume (25ul) of whole blood and can be used to determine the proportion of helper T cells, cytotoxic T cells, Natural Killer cells, neutrophils and eosinophils within the sample. This allows the simultaneous phenotyping of whole herds of cattle. 
Type Of Material Technology assay or reagent 
Year Produced 2014 
Provided To Others? Yes  
Impact This methodology has been used to validate previous findings that particular cell phenotypes are associated with increased resistance to disease in cattle. By increasing the number of cattle which can be phenotyped in this manner, it has been possible to estimate the heritabilities of these cellular immune traits in dairy cattle. 
 
Title High-throughput immune profiling of innate immune responsiveness in cattle 
Description A method has been developed to provide an estimate of immune responsiveness of bovine blood leukocytes to a range of innate immune stimuli including ligands for Toll-like Receptor (TLR) 1/2, TLR4, TLR5 and TLR7/8. Low volumes (100ul) of whole blood are stimulated with TLR ligands for 24 hours. Released cytokines are quantified by ELISA based methods. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2015 
Provided To Others? Yes  
Impact Using this method we have identified significant variation in the responsiveness of dairy cattle blood leukocytes to TLR stimulation. Responsiveness varies significantly with age but does not appear to be altered by selection for high productivity. This method will allow us to determine the implications of variation in innate immune responsiveness on dairy cow health, productivity and vaccine responsiveness. 
URL https://connect.innovateuk.org/documents/3285671/29811791/KTN_BSAS-+Noronha+Report.pdf/9b66bfbf-5e29...
 
Title High-throughput immune response phenotyping of ruminants 
Description This technique allows the characterisation of T-helper polarisation in ruminants. Whole blood is stimulated with a non-specific T cell mitogen and the type and quantity of cytokine released is assessed. This method can then be applied at the population level to determine the effects of other variables (genetic, environmental) on the adaptive immune response, and to determine how variation in adaptive immune response is associated with health and productivity traits. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2017 
Provided To Others? Yes  
Impact This research tool has been applied to Scottish Government commissioned research to explore the impact of selection for productivity on adaptive immune responses in sheep. 
 
Title Mid infrared spectral data based phenotype prediction tool 
Description A software workflow developed in Microsoft SQL for the storage, processing, calibration and preparation for reporting of mid infrared (MIR) -predicted phenotypes, implementing quality assurance checks, dynamic and flexible to the inclusion of additional traits and tailored for use in a commercial environment. Code has additionally been ported to the (open source) Python programming language and can be used on most operating systems. 
Type Of Material Improvements to research infrastructure 
Year Produced 2015 
Provided To Others? Yes  
Impact The tool is currently being used to advise farmers in the UK of cow energy traits within their herds. As the MIR spectral data is a byproduct of the routine milk recording process, the energy trait information can be generated in a completely non-invasive manner and hence, enable improvements in animal welfare. Moreover, the tool is being used to predict important immune-associated traits linked with health and fertility traits. 
 
Title Immune_Dairy Database 
Description The database incorporates measurements of a number of immune traits in a herd of dairy cattle over 15 sampling timepoints over an 24 month period together with health, production and reproductiion traits. The immune traits have been measured in both blood and milk samples as part of the currently funded BBSRC grant andhas been incorporated into an overall model to predict health events in dairy cattle. This database consists of 8 cellular immune traits, plus a number of paired immune measurements in serum and milk (cytokine, acute phase protein, natural anitbody), with each trait being measured in a total of 3000 individual samples. 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? No  
Impact The database has been used to estimate the heritabilities of a number of immune traits (e.g. CD4:CD8 T cell ratio, %CD8 T cells, %NK cells) which are associated with resistance to disease in dairy cattle. 
 
Description The influence of trace element levels on immunity and health in dairy cattle 
Organisation University of Aberdeen
Department The Rowett Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Serum samples collected from dairy cattle with known health, production and immune trait data have been supplied to the research partner for trace element analysis to determine if levels of trace elements are associated with variation in health, production and immune status.
Collaborator Contribution The partner has measured 15 trace elements in the supplied serum samples and the results incorporated into the Immune_Dairy database.
Impact Using the data generated from this collaboration, genetic parameters of serum and milk trace elements were estimated and have been published in the Journal of Dairy Science (doi: 10.3168/jds.2019-16960). This collaboration was multidisciplinary, involving quantitative geneticists, immunologists, and nutritionalists.
Start Year 2014
 
Description British Cattle Breeders Club meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Poster presentations highlighting results of the genetic analysis of immune-associated traits as well as results from using mid infrared spectroscopy of milk samples to predict immune-associated traits. Prompted questions and discussion.
Year(s) Of Engagement Activity 2017
 
Description British Society of Animal Science Annual Conference 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presented a paper discussing relationships of cellular immune-associated traits with health, fertility and production traits in dairy cows. Talk generated questions and discussion.
Year(s) Of Engagement Activity 2017
 
Description British Society of Animal Science Annual Conference 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Paper presented discussing Immune-associated traits measured in milk as proxies for blood serum measurements in dairy cows. Questions and discussion post presentation.
Year(s) Of Engagement Activity 2018
URL https://www.cambridge.org/core/journals/advances-in-animal-biosciences/issue/9FCE40A5DF9AA24026CD18B...
 
Description Edinburgh Immunology Group Annual Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Invited presentation on Fitness and Survival Consequences of Immune Variation in Ruminant Populations. The audience consisted of immunologists (including world leaders in the field) within the Edinburgh area and the talk generated useful feedback and discussions around immune variation in ruminants.
Year(s) Of Engagement Activity 2014
 
Description Presentation (BSAS_ 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Main purpose to present information to other academic audiences (collaborators, peers etc)
Year(s) Of Engagement Activity 2015
 
Description Presentation (poster-WCGALP) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact The main aim of the poster presentation was to share information with other academics (peers, collaborators etc). The poster generated significant interest and questions. Handouts with further information were given out.
Year(s) Of Engagement Activity 2014
 
Description Presentation to Scientific peers and dairy industry stakeholders at EAAP, 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Scientific presentation at EAAP (European Federation of Animal Sciences, Belfast 2016): Investigating the use of Mid Infrared (MIR) spectral data to predict dairy cow cellular immune traits. Authors: SJ Denholm, SL Smith, TM McNeilly, V Hicks and E Wall. This talk was given to an audience of scientific peers, students and industry (~100 people) and highlighed the use of MIR to predict immune associated traits in dairy cattle.
Year(s) Of Engagement Activity 2016
 
Description Press release to launch project 
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 Media (as a channel to the public)
Results and Impact The press release sparked interest from the Dartington Cattle Trust and discussions on the potential impacts of the project.
Year(s) Of Engagement Activity 2013
URL http://www.bbsrc.ac.uk/news/food-security/2013/130%20613-pr-funding-for-predicting-health-of-dairy-c...
 
Description Royal Highland Show 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The stand generated much interest from school children (from primary through to S6), farmers, the press and the general public. As this was an open event there were many opportunities for discussion and knowledge transfer.
Discussions with farmers highlighted the usefulness of such a tool that could come out of the current area of research. School children and the general public gained a better understanding of animal science techniques and the ability to conduct animal research without the requirement of invasive sampling.
Year(s) Of Engagement Activity 2015
URL http://www.sruc.ac.uk/srucrhs
 
Description SEFARI Gateway Case study on Healthy cow, healthy milk? Identifying traits that are mutually beneficial to the cow and the consumer. 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact A case study highighting the work conduced on milk samples obtained from this project was produced for the SEFARI - Scottish Environment, Food and Agriculture Research Institutes - website. This website is targetted to key stakeholders e.g. industry, research community, policy groups as well as the general public.
Year(s) Of Engagement Activity 2022
URL https://sefari.scot/research/healthy-cow-healthy-milk
 
Description World Congress on Genetics Applied to Livestock Production 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Presentation given in the "Biology - Disease Resistance" session which was joint with the International Committee for Animal Recording (ICAR). Discussion of genome-wide associations of immune-associated traits in dairy cows.
Year(s) Of Engagement Activity 2018
URL http://www.wcgalp.org/