Novel approaches to enhance disease resistance in ruminants?-Breeding for geographically important TLR SNPs: The ruminant TLR consortium

D. W. Burt, T. J. Coffey, S. Chang, E. J. Glass, D. Haig, J. C. Hope, O. Jann, J. Salt, C. Warkup, D. Werling

Research output: Contribution to journalMeeting abstractpeer-review

Abstract

Opportunistic infections resulting from intensive husbandry of livestock have become one of the major problems in modern animal production. As bacterial resistance to antibiotics is expected to escalate, novel approaches to disease prevention will need to be established. One approach includes breeding for disease resistance by selecting the 'fittest' innate immune system. The innate immune system recognises pathogens by means of pattern recognition receptors, such as Toll-like receptors (TLRs). These interact with various microbial components and induce a specific innate immune response. Several polymorphisms in TLR genes have been described for the human and murine system that influence the abilities of affected TLRs to recognise pathogen-derived molecules-rendering individuals more or less susceptible to infection. The first nucleotide polymorphisms (SNPs) in ruminant TLRs were characterised in bovine TLR4, the receptor for gram-negative bacteria. Analysis of codon-based models of selection identifies many sites in TLR4 under positive selection in the region 261-375 residues. This region is located in the middle of the extracellular domain between clusters of leucine-rich-repeats (LRRs) and is predicted to be the ligand binding domain. We would expect a higher frequency of non-synonymous SNPs to map to his domain. Indeed, the first non-synonymous SNPs map to this region. We have cloned and mapped ten bovine TLRs, and are currently in the progress of functionally characterising these TLRs. In addition, TLR genes from sheep are also being cloned and characterised. TLRs from different cattle and sheep breeds are currently been analysed for the presence of synonymous and non-synonymous SNPs. Our data suggest a heterogeneity in extracellular regions of TLR genes, which may be advantageous to promote a specific disease resistance, and represent a new approach to select disease resistance-based on a geographical distribution of TLR SNPs. Breeding of ruminants with TLRs that confer a 'fitter' innate immune system resulting in disease resistance could play a major role in the future of the farming industry both in the UK and worldwide.
Original languageUndefined/Unknown
Pages (from-to)212
Number of pages1
JournalVeterinary Immunology and Immunopathology
Volume128
Issue number1-3
DOIs
Publication statusPublished - 2009
Event 8th International Veterinary Immunology Symposium (8th IVIS) - Ouro Preto, Brazil
Duration: 15 Aug 200719 Aug 2007

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