Gene set enrichment analysis of SNP data in dairy and beef cattle with bovine respiratory disease

Abstract

Bovine respiratory disease (BRD) is a complex disease that is associated with infection by bacterial and viral pathogens when cattle fail to adequately respond to stress. The objective of this study was to use gene set enrichment analysis of SNP data (GSEA-SNP) and a network analysis (ingenuity pathway analysis) to identify gene sets, genes within gene sets (leading-edge genes) and upstream regulators associated with BRD in pre-weaned dairy calves and beef feedlot cattle. BRD cases and controls were diagnosed using the McGuirk health scoring system. Holstein calves were sampled from commercial calf-raising facilities in California (1003 cases and 1011 controls) and New Mexico (376 cases and 372 controls). Commercial feedlot cattle were sampled from Colorado (500 cases and 499 controls) and Washington (504 cases and 497 controls). There were 102 and 237 unique leading-edge genes identified in the dairy calf and beef cattle populations respectively. Six leading-edge genes (ADIPOQ, HTR2A, MIF, PDE6G, PRDX3 and SNCA) were associated with BRD in both dairy and beef cattle. Network analysis identified glucose as the most influential upstream regulator in dairy cattle, whereas in beef cattle, TNF was the most influential upstream regulator. The genes, gene sets and upstream regulators associated with BRD have common functions associated with immunity, inflammation and pulmonary disease and provide insights into the mechanisms that are critical to BRD susceptibility in cattle.

The EDN2 rs110287192 gene polymorphism is associated with paratuberculosis susceptibility in multibreed cattle population

“…Due to the relatedness of mycobacterial pathogens such as MAP, Mycobacterium tuberculosis and Mycobacterium bovis, loci that provide less genetic susceptibility to one pathogen might afford some protection to the other organism. In fact, loci on BTA3 where we identified association for pTB susceptibility in the current study, overlapped with loci previously reported in the literature that were associated with bovine tuberculosis susceptibility [28] and bovine respiratory disease susceptibility [29].…”

The Immunology of Bovine Respiratory Disease

“…In the same study, TNF was identified as the most significant upstream regulator in beef cattle, influencing 64 downstream genes that were associated with the immune response. 79 Comparisons between the beef and dairy populations in this studied identified 6 BRD-associated SNPs that were shared between the groups, located in the genes ADIPOQ, HTR2A, MIF, PDE6G, PRDX3, and SNCA. 79 All 6 genes are known to be involved in down-regulating TNF production and in the metabolism of reactive oxygen species.…”

“…79 Comparisons between the beef and dairy populations in this studied identified 6 BRD-associated SNPs that were shared between the groups, located in the genes ADIPOQ, HTR2A, MIF, PDE6G, PRDX3, and SNCA. 79 All 6 genes are known to be involved in down-regulating TNF production and in the metabolism of reactive oxygen species. 79 It is expected that the next decade will bring continued advancements in understanding of the genetic components of this pervasive syndrome.…”

“…79 All 6 genes are known to be involved in down-regulating TNF production and in the metabolism of reactive oxygen species. 79 It is expected that the next decade will bring continued advancements in understanding of the genetic components of this pervasive syndrome.…”

Maternal genes and pathways affecting birth weight and weaning weight traits in sheep: A GWAS and pathway enrichment analysis

“…being a member of a specific pathway) which are identified by significant (with comfortable threshold) SNPs of GWAS, is tested for over-representation in a specific pathway [9]. Recently a growing interest in gene set enrichment analysis has been observed in dairy cattle [8,10,11]. However, there are no published reports of gene set analysis of sheep GWAS dataset.…”