Single nucleotide polymorphisms in bovine chemokine and toll-like receptors : impacts on disease susceptibility and productivity in dairy cattle

Russell, Christopher David (2013) Single nucleotide polymorphisms in bovine chemokine and toll-like receptors : impacts on disease susceptibility and productivity in dairy cattle. PhD thesis, University of Nottingham.

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Bovine mastitis is recognised worldwide as the most important and costly disease affecting dairy cattle. The reduction of herd mastitis rates is crucially needed to improve animal welfare and profitability, and lessen the reliance on antibiotics.

Single nucleotide polymorphisms (SNPs) within genes that have a critical role in the innate immune response, such as Toll-like receptors (TLRs) and the chemokine receptors CXCR1 and CXCR2, could impact on establishment and progression of intramammary infection, and therefore influence an animal’s susceptibility to disease. The genetic selection of animals with favourable TLR and CXCR1/2 mutations, with no impact on production traits, could be incorporated into dairy breeding programmes.

In order to investigate any associations with clinical mastitis (CM) incidence and milk quality and quantity, this study identified and analysed SNPs alongside actual CM and production data from a Holstein-Friesian herd. This revealed 46 SNPs, 9 of which are novel, within boTLR1/4/5, boCD14, boCXCR1 and boCXCR2; selected SNPs were then tested for association with CM. This is the first report of boTLR1 SNPs and a non-coding boCXCR1 SNP that associate significantly with susceptibility to CM. Favourable linkage of reduced CM with increased milk fat and protein was observed, indicating selection for these markers would not be detrimental to milk quality.

Furthermore, this study provides evidence that some of these SNPs underpin functional variation in bovine TLR1 and CXCR1, and possibly underlie an immunological mechanism for disease susceptibility. SNPs in boTLR1 and boCXCR1 were significantly associated with impaired transcript levels in milk somatic cells. In addition boTLR1 SNPs associated with impaired cytokine responses from cell populations when exposed to ligand or heat-killed mastitis-causing bacteria. The potential impact of boTLR1 variation on the immune response to Staphylococcus aureus is demonstrated, and this has implications for boTLR1-mediated immune responses to other pathogens.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Coffey, T.
Leigh, J.
Subjects: Q Science > QR Microbiology > QR171 Microorganisms in the animal body
S Agriculture > SF Animal culture
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Item ID: 13201
Depositing User: EP, Services
Date Deposited: 13 Nov 2013 10:44
Last Modified: 15 Sep 2016 22:47

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