Genetic Regulation of Biomarkers as Stress Proxies in Dairy Cows

Abstract

Stress in livestock reduces productivity and is a welfare concern. At a physiological level, stress is associated with the activation of inflammatory responses and increased levels of harmful reactive oxygen species. Biomarkers that are indicative of stress could facilitate the identification of more stress-resilient animals. We examined twenty-one metabolic, immune response, and liver function biomarkers that have been associated with stress in 416 Italian Simmental and 436 Italian Holstein cows which were genotyped for 150K SNPs. Single-SNP and haplotype-based genome-wide association studies were carried out to assess whether the variation in the levels in these biomarkers is under genetic control and to identify the genomic loci involved. Significant associations were found for the plasma levels of ceruloplasmin (Bos taurus chromosome 1—BTA1), paraoxonase (BTA4) and γ-glutamyl transferase (BTA17) in the individual breed analysis that coincided with the position of the genes coding for these proteins, suggesting that their expression is under cis-regulation. A meta-analysis of both breeds identified additional significant associations with paraoxonase on BTA 16 and 26. Finding genetic associations with variations in the levels of these biomarkers suggests that the selection for high or low levels of expression could be achieved rapidly. Whether the level of expression of the biomarkers correlates with the response to stressful situations has yet to be determined.

The Transition Period Updated: A Review of the New Insights into the Adaptation of Dairy Cows to the New Lactation

“…A clear explanation behind the mechanism responsible for the onset of such an early and persistent inflammatory condition in some animals still lacking. Recently, Milanesi et al [48] found the expression of two inflammatory biomarkers related to the acute phase response (paraoxonase and ceruloplasmin) to be primarily under cis regulation in dairy cattle. This significant genetic association was identified in two dairy breeds (Italian Holstein and Italian Simmental), characterized by highly different selection histories, immune-metabolic status and production performances [49][50][51].…”

“…Thus, a different expression of inflammatory biomarkers driven by genotype could account for the different inflammatory conditions found by Cattaneo et al [22] before the dry-off. Despite that, the relationship between the candidate causative variants identified by Milanesi et al [48] and the animals' performances during the TP has not yet been investigated, and the contribution of genotype on the successful adaptation of dairy cows to the new lactation still to be elucidated.…”

“…For example, Omnigen-AF (OAF) is known as an immune modulator that could be included in the diet of dairy cows from dry-off to the first month of lactation, providing positive effects on leukocyte function and a consequent reduction of the incidence of infectious diseases in TP [24,107]. Although a direct effect of OAF on the gene expression of neutrophils has been reported [108], a recent study found no effects on neutrophils diapedesis measured in-vivo or on the amelioration of liver metabolism and inflammation of dairy cows receiving the feed additive [48,109]. Nevertheless, the same study described dairy cows receiving OAF to have an increased abundance of lymphocytes at the blood level and improved leukocyte function after ex-vivo stimulation with LPS (lower lactate production and lower glucose consumption).…”

Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype

“…Preliminary findings on the levels of serum proteins in cattle and their correlation with degrees of mycobacterial infection have led to the discrimination of clinical and subclinical bTB and different stages of bovine paratuberculosis (Johne's disease) from not infected cattle and exposed cattle ( 29 – 32 ). Furthermore, analyses of concentration in serum of proteins that impact the immune system and macrophage function, i.e., adiponectin, ceruloplasmin, and conglutinin ( 33 – 35 ), have revealed that those are under genetic control and heritability ( 36 – 38 ), and a negative association with the predisposition of respiratory infectious diseases in cattle ( 36 , 37 , 39 ) with implications in bTB ( 35 ). These findings suggest that identifying serum proteins for resistance against bTB is possible in cattle and since non-specific serum proteins have a role in protective immunity, measuring the level of serum proteins may be a helpful trait in such a breeding strategy.…”

Data_Sheet_1.pdf

“…Preliminary findings on the levels of serum proteins in cattle and their correlation with degrees of mycobacterial infection have led to the discrimination of clinical and subclinical bTB and different stages of bovine paratuberculosis (Johne's disease) from not infected cattle and exposed cattle (29)(30)(31)(32). Furthermore, analyses of concentration in serum of proteins that impact the immune system and macrophage function, i.e., adiponectin, ceruloplasmin, and conglutinin (33)(34)(35), have revealed that those are under genetic control and heritability (36)(37)(38), and a negative association with the predisposition of respiratory infectious diseases in cattle (36,37,39) with implications in bTB (35). These findings suggest that identifying serum proteins for resistance against bTB is possible in cattle and since nonspecific serum proteins have a role in protective immunity, measuring the level of serum proteins may be a helpful trait in such a breeding strategy.…”