Association study of single nucleotide polymorphisms inJAK2andSTAT5Bgenes and their differential mRNA expression with mastitis susceptibility in Chinese Holstein cattle

Abstract

The JAK-STAT pathway plays a key role in mediating immune responses. The genetic effects of single nucleotide polymorphisms (SNPs) in JAK2 and STAT5B were investigated for serum cytokines, mastitis indicators and productions traits in a population of 468 Chinese Holstein cattle. Pooled DNA sequencing revealed one SNP (BTA8:g.39645396A>G) in JAK2 and two SNPs (BTA19:g.43673888A>G and BTA19:g.43660093T>C) in STAT5B. A fixed effect model considering the effects of SNPs, parity, herd, season and year of calving was used by way of the general linear model procedure of sas. Genotype frequencies of these SNPs in the population were in Hardy-Weinberg equilibrium (P > 0.05). A novel SNP (g.39645396A>G) in JAK2 was predicted to change the amino acid from lysine to asparagine and was significantly associated with the somatic cell count (SCC) and somatic cell score (SCS), whereas g.43673888A>G in STAT5B was significantly associated with SCC, SCS and interleukin-4 (IL-4) (P < 0.05). The dominant effect of g.39645396A>G in JAK2 was significant for SCS, and its additive effect was significant for SCC, whereas the dominant effect of g.43673888A>G in STAT5B was significant for SCS and IL-4 (P < 0.05). The combination of g.39645396A>G in JAK2 and g.43673888A>G in STAT5B showed a significant effect on SCC, SCS, IL-4 and TNF-α (P < 0.05). As for mRNA expression analysis, the AA genotype g.39645396A>G and GG genotype g.43673888A>G indicated higher mRNA expression level and were significantly different from other genotypes (P < 0.05). The results imply that JAK2 and STAT5B genes could be useful candidate genes, and the identified polymorphisms might potentially be strong genetic markers for selection of dairy cattle against mastitis development.

Comparative Analysis of V-Akt Murine Thymoma Viral Oncogene Homolog 3 (AKT3) Gene between Cow and Buffalo Reveals Substantial Differences for Mastitis

“…In the PI3K pathway AKT isotopes are the crucial signaling molecules which regulate cell growth, proliferation, survival, and metabolism [ 13 ]. For tackling diseases, their immunity related functions are important [ 38 , 39 ]. AKT is also involved in the regulation of inflammatory cytokines with proinflammatory property as shown in the TLR signaling pathway.…”

Three Novel Players: PTK2B, SYK, and TNFRSF21 Were Identified to Be Involved in the Regulation of Bovine Mastitis Susceptibility via GWAS and Post-transcriptional Analysis

“…However, AKT1, as a key player in the Jak2/STAT5 pathway, plays an important role in the regulation of differentiation, secretion, survival, and proliferation of mammary epithelial cells as well as mammary remodeling and lactation sustainability in dairy cows (90, 97–100). JAK2 and STAT5, two key players in the immune response, are associated with cow mastitis susceptibility (11, 101). Mastitis caused by bacterial infection of the mammary gland induces IL8 expression (102), and IL-8 plays an important role in the recruitment and degranulation of neutrophils in mammary gland (13).…”

Significant genetic effects of JAK2 and DGAT1 mutations on milk fat content and mastitis resistance in Holsteins

“…Our findings demonstrated that SNPs at locus 39652267C/T and 39645396C/T in JAK2 had a significant association with milk fat percentage. However, previously, our research group did not find any link of these SNPs in JAK2 with milk production traits, including milk fat percentage (Usman et al ., 2014, 2015). In exon 16 of JAK2, phosphorylation occurs at 39652267A/G which affects the STAT gene that regulates the transcription of different genes in the nucleus and plays a key role in varieties of processes (Szewczuk, 2015).…”

“…Cytokine-based marker-assisted selection could allow progress toward mastitis resistance and improvement in milk production traits. In the present study, we selected the SNPs in JAK2 from previous studies of our research team (Usman et al ., 2014, 2015) due to its key role in mastitis resistance. The DGAT1 has widely been studied and reported for its role in milk production traits in dairy cattle (Grisart et al ., 2004; Schennink et al ., 2007; Yuan et al ., 2007; Molee et al ., 2012).…”