Association of variants in innate immune genes TLR4 and TLR5 with reproductive and milk utility traits in Czech Simmental cattle
Abstract
The bovine genes TLR4 and TLR5, which encode antibacterial toll-like receptors of the innate immune system, were screened for polymorphisms in Czech Red Pied (Czech Simmental) cattle to identify variants associated with reproduction, udder health and milk production traits, namely, milk fat percentage, fat yield, protein percentage and protein yield, total milk yield, somatic cell score, udder health index, milkability, lactation persistency, incidence of cystic ovaries, early reproductive disorders, calving ease, maternal calving ease, production longevity, and calf vitality index. Gene variants were discovered by hybrid resequencing using HiSeq X-Ten and PacBio technologies and then individually genotyped.
Associations between 7 polymorphisms of each gene with phenotypic traits were found in 18 combinations using one-way ANOVA with subsequent Benjamini- Hochberg tests. Both the TLR4 variants rs8193060 and rs8193072 (9422T>C and 10310T>G in reference AC000135.1, respectively) and the TLR5 variants ss73689429, rs55617187 and rs55617288 (545T>C, 3714C>T and 4626T>C in EU006635, respectively) were associated with increased incidence of cystic ovaries and a general index of early reproductive disorders.
Variants 610C>T (rs43578094) with 9422T>C of TLR4 and 1736C>T (ss73689443) of TLR5 were associated with calving ease. In addition, 9422T>C and 7999A>G (rs43578100) in TLR4 were associated with production longevity.
The association of 610C>T with calf vitality index might reflect calfhood infections. By contrast to TLR4, 488C>G, 1736C>T and 3891C>T in TLR5 were associated with milk production traits.
The discrepancy in the predicted impacts on protein function points at the role of haplotypes. Positional matches with known QTLs for calving ease, namely, #43837 on chromosome 8 and #48258 on chromosome 16, endorse the causative roles of TLR4 and TLR5, respectively.
The TLR polymorphism effect on female reproduction traits can also be mediated by non-immune functions of TLRs in myometrial signaling, consistently with the known role of TLRs in model species.