Aetiopathogenesis and genomic architecture of resistance to claw horn disruption lesions in dairy cattle

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Maintaining good foot health is one of the most critical challenges the dairy industry faces today. This is because poor foot health leads to reduced mobility of the animal and causes lameness. The latter is a debilitating and painful condition, and is described as one of the clearest indicators of compromised welfare in dairy cattle and one of the most important factors for the involuntary replacement of animals. No other common condition is associated with such visible signs of pain and, as such, cow lameness damages the public's perception of the industry. Recent studies have suggested that nearly half the dairy cows in the UK face reduced mobility and lameness issues at some point in their life, costing the dairy sector approximately £250 million annually.Painful foot lesions account for more than 90% of reduced cow mobility and lameness cases. These lesions broadly fall under two categories: infectious diseases such as digital dermatitis and interdigital phlegmon, and non-infectious claw horn disruption lesions (CHDL) such as sole haemorrhages, sole ulcers and white line disease. CHDL are the most prevalent conditions associated with impaired mobility and pain in dairy cattle in the UK and worldwide. In a recent study by our group, 44% of cows developed CHDL during 12 months of monitoring (26%, 12% and 19% for sole haemorrhages, sole ulcers and white line disease, respectively).Despite the importance of CHDL, the reasons leading to their development have not yet been fully described. The anatomic structure of the foot, animal hormonal and immune profiles, inflammation around calving, animal metabolism, and management practices have been thought to contribute. There are also genetic differences between individual animal susceptibility to CHDL development. In this project, all these factors will be studied together using a large number of animals (3,000 Holstein cows) raised in four UK commercial farms. As a result, the project will (i) determine and quantify the impact of different factors affecting the development of CHDL, (ii) identify and quantify the genetic background of animal resistance to the development of CHDL and (iii) develop practical breeding strategies and tools to reduce the incidence of CHDL while maintaining improvement in other important animal traits (fertility, resistance to other diseases and productivity). To achieve its objectives, the project will draw on complementary expertise in animal science, veterinary medicine, genetics, biotechnology, bioinformatics, molecular pathology, immunology, microscopy and epidemiology.Animals recruited for this project will be pregnant cows. The farms where these animals are raised have already been identified and have agreed to participate. Animals will be closely monitored by a qualified veterinarian from 60 days before calving through to the first half of the ensuing lactation. Systematic recording of CHDL, the thickness of the digital cushion (a protective anatomical structure of the foot), hormonal levels in blood, specific proteins in blood and tissues indicative of inflammation, acid levels in blood indicative of altered metabolism, and cow activity and resting patterns will take place, generating a unique database of relevant information. Individual cattle genomic profiles will be generated and analysed together with cow measurements to assess the environmental and genetic impact on CHDL. Using advanced sequencing technologies will try to understand the underlying molecular mechanisms that lead to the development of foot lesions. Finally, simulation studies will be designed to evaluate different breeding strategies and tools with the aim to breed resistance to CHDL into the dairy cattle population.Outcomes of this project may improve considerably animal health and welfare by underpinning the development of efficient management practices, new breeding tools and novel pharmaceutical interventions.