Inferring effects of vitamin D-related gene polymorphisms and gene expressions on blood vitamin D concentrations, immune response and health in dairy cows

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Dairy cows experience a negative energy balance in early lactation, implying an increased risk for immunosuppression and disease susceptibility. An important metabolite involved in corresponding physiological functions and pathways is vitamin D, suggesting detailed evaluations from a nutritional perspective and targeted vitamin D supplementation via feed. Genetic aspects of vitamin D regulations mostly have been inferred in humans. In dairy cows, the relationships between genetic variants, blood vitamin D levels and health are unknown, but provide essential insights to optimise breeding strategies for an improved immune status and disease resistance. Both applicants Prof. Eder and Prof. König identified associations between polymorphisms of the CYP2R1 gene with blood vitamin D levels and diseases in dairy cows. Such first insights into genetic vitamin D mechanisms suggest utilisation of dense genome sequences to identify the underlying genetic variants and pathways involved in vitamin D metabolism, and to infer further causalities with cow health. Therefore, the project aims at the identification of genetic polymorphisms of 16 genes involved in vitamin D metabolism using very detailed shotgun sequencing with target enrichment (50x coverage), and to study effects of polymorphisms on vitamin D metabolite concentrations, disease occurrence and immune response in dairy cows. In this regard, we will focus on measurements of blood vitamin D during the challenging early lactation period, on deep health trait recording, on immune parameter measurements, genome sequencing and gene expressions considering 300 German Holstein dairy cows kept in two research herds with established individual feeding possibilities. In both herds, the cows will be allocated into two feeding groups with different vitamin D supplementation levels. We hypothesize that polymorphisms in genes involved in vitamin D metabolism, the respective transcriptomic profiles and their interactions with feeding, immune response and genetic merit groups for milk yield significantly affect vitamin D metabolism and disease occurrence in dairy cows. For the research herd cows as well as for ~20,000 cows from contract herds, (imputed) WGS data (30x coverage) is already available. The existing WGS data will be used for genome-wide associations for immune response indicators and for diseases. Finally, we compare association signals for the specific diseases with association signals for immunity measures, indicating a) health traits, which can be used as immunity markers, and b) SNPs and chromosome segments with specific relevance for genomic predictions. Additionally, results from gene expression analyses (expression QTL) will be considered in enhanced genomic predictions.