Transcriptome profiles of whole blood in Italian Holstein and Italian Simmental lactating cows diverging for genetic merit for milk protein

The aim of the research was to investigate the variation of gene expression in the blood of lactating cows in relation to the genetic merit for productive traits. For the study, 24 Italian Holstein (IH) cows from a single farm and 24 Italian Simmental (IS) cows from a second farm were selected. Cows were in mid-lactation, and farms had similar management and feeding conditions. For each breed, cows were separated into 3 classes of estimated breeding value (EBV) for milk protein yield (EBVp), namely, 8 cows with low EBVp (low group, LG), 8 cows with high EBV (high group, HG), and the 8 cows closest to the median (medium group, MG). Gene expression was measured on blood with a whole-transcriptome bovine microarray, and data of LG and HG were expressed relative to MG. The number of differentially expressed genes between the low and high EBVp groups were 443 for IS and 281 for IH cows. The IS cows had a greater number of genes (398 vs. 241 in IH cows) with opposite expression in the high and low EBV groups, compared with the MG. In IS cows, the largest number of pathways affected were within the KEGG subcategories of "energy metabolism," "lipid metabolism," and "metabolism of cofactors and vitamins." Furthermore, the "glutathione metabolism" pathway was markedly affected, with GSTM1 (from glutathione-S-transferase family), GSS (glutathisone synthetase), and G6PD (glucose-6-phosphate dehydrogenase) upregulated in the IS HG but downregulated in the IS LG group. The "intestinal immune network for IgA production" pathway had 2 bovine leukocytes antigen (BoLA-DQ) genes, and the B-cell activating factor of the TNF superfamily (TNFSF13B) upregulated in the IS LG group and downregulated in the IS HG group. The IH cows had the highest number of affected pathways in the "metabolism" and "organismal systems" categories, the latter with 5 out of 10 subcategories relative to the immune system. Within the "T cell receptor signaling pathway," the IH HG cows had upregulation of the CD1d, CD4, and CD3 antigens and downregulation of the NFkB subunit ReLa gene. This study revealed that specific metabolic and immunological pathways are directly related to genetic merit, and could be considered a signature of quantitative selection. Starting from these preliminary observations, the comparison of differentially expressed genes among animals with different EBVp seems a promising approach to unravel molecular response at a blood level associated with productive traits.