title: Identification of single nucleotide polymorphisms in the bovine Toll-like receptor 1 gene and association with health traits in cattle.
abstract: Bovine mastitis remains the most common and costly disease of dairy cattle worldwide. A complementary control measure to herd hygiene and vaccine development would be to selectively breed cattle with greater resistance to mammary infection. Toll-like receptor 1 (TLR1) has an integral role for the initiation and regulation of the immune response to microbial pathogens, and has been linked to numerous inflammatory diseases. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) within the bovine TLR1 gene (boTLR1) are associated with clinical mastitis (CM).Selected boTLR1 SNPs were analysed within a Holstein Friesian herd. Significant associations were found for the tagging SNP -79 T > G and the 3'UTR SNP +2463 C > T. We observed favourable linkage of reduced CM with increased milk fat and protein, indicating selection for these markers would not be detrimental to milk quality. Furthermore, we present evidence that some of these boTLR1 SNPs underpin functional variation in bovine TLR1. Animals with the GG genotype (from the tag SNP -79 T > G) had significantly lower boTLR1 expression in milk somatic cells when compared with TT or TG animals. In addition, stimulation of leucocytes from GG animals with the TLR1-ligand Pam3csk4 resulted in significantly lower levels of CXCL8 mRNA and protein.SNPs in boTLR1 were significantly associated with CM. In addition we have identified a bovine population with impaired boTLR1 expression and function. This may have additional implications for animal health and warrants further investigation to determine the suitability of identified SNPs as markers for disease susceptibility.
authors.affiliation: Bovine Genomics Group, Institute for Animal Health, Compton, Berkshire, RG20 7NN, UK. tracey.coffey@nottingham.ac.uk.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Russell
authors.forename: Stephanie
authors.initials: S
authors.lastname: Widdison
authors.forename: James A
authors.initials: JA
authors.lastname: Leigh
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Coffey
mesh_terms: D000818:Animals; D002417:Cattle; D002452:Cell Count / Q000662:veterinary; D005260:Female; D056726:Genetic Association Studies / Q000662:veterinary; D005819:Genetic Markers; D007774:Lactation; D008414:Mastitis, Bovine / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D008892:Milk / Q000737:chemistry* / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D020641:Polymorphism, Single Nucleotide; D051194:Toll-Like Receptor 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D005819:Genetic Markers; D051194:Toll-Like Receptor 1