Epigenetic Inheritance of Maternal Disease Status in Dairy Cattle and Effect on Offspring Performance

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Commodities

• Animals: bovine
• Animal Products: dairy

Practices

• Animal Production: animal protection and health, genetics, livestock breeding

This project aims to identify associations between DNA methylation and disease status and how these associations may influence performance in dairy cattle. Disease is costly to the dairy industry and negatively impacts animal welfare. Mastitis alone is estimated to cost the U.S. industry $2 billion annually. Genetic selection for disease resistance is possible but the trait is largely impacted by environmental factors that modulate gene expression through epigenetic mechanisms such as DNA methylation. This project will consist of a whole-herd retrospective analysis of the Cornell Veterinary School Teaching Dairy (VTD) and DNA methylation analysis on a subset of animals. Performance outcomes of offspring such as production, fertility, health, and longevity will be compared based on their dam’s history of disease using electronic records of the farm. Regions of differential methylation between dam health groups, in offspring pre- and post-disease, and in offspring with differing dam disease history will be identified to characterize a possible biologic explanation for any observed associations in health and performance. This project is a pilot project for a more extensive study of epigenetic associations with disease in dairy cattle. Understanding the lasting and transgenerational effects of disease will help producers make educated management decisions. Characterizing DNA methylation as a source of phenotypic variation will also help improve genetic prediction models. These two factors will increase farmer profitability with improved selection and management of dairy cattle.

This project will consist of two methodologies: a retrospective whole-herd record analysis and DNA methylation sequencing on a subset of animals. First, an analysis of the Cornell Veterinary School Teaching Dairy (VTD) historical health and performance records will be conducted to validate the results of the Carvalho study in this herd i.e., calculate associations between maternal disease status and offspring disease risk and performance. Second, genome-wide DNA methylation analyses of a subset of animals will be conducted to investigate epigenetic mechanisms underlaying the relationships observed in the first analysis. Differences in DNA methylation between sick and healthy animals pre- and post-disease event, whether these are inherited by offspring, and whether these methylation differences have effects on health, growth, production, fertility, and longevity will be investigated.

Specific objectives within the study to meet our goal of improved understanding of the relationship between DNA methylation, disease, and phenotypic variation are as follows.

• Objective 1: Investigate associations between dam history of disease and offspring’s susceptibility to disease, production, fertility, longevity, and genetic merit using a retrospective study design of the VTD
• Objective 2: Characterize associations between DNA methylation and disease status
• Objective 3: Characterize DNA methylation inheritance with a focus on dam disease status and the association with offspring disease susceptibility
• Objective 4: Identify differentially methylated regions with putative biological functions relevant to health, growth, production, fertility, and longevity relationships observed