Codner, Gemma Frances
Assessing MHC class I diversity in dairy cattle populations.
PhD thesis, University of Glasgow.
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The gene dense major histocompatibility complex (MHC) region, present in all jawed vertebrates, encodes molecules involved in self-non-self discrimination and the binding and presentation of antigenic peptides to T cells during the adaptive immune response. Variation in MHC genes is thought to be driven largely by pathogen-mediated selection, with diversity at MHC loci believed to benefit populations by allowing responses to rapidly evolving disease pathogens. However, in economically important dairy cattle, there are concerns that intensive selection for production and fitness traits may override natural selection. It had been hypothesised that these focussed dairy breeding practices may lead to a reduction in MHC diversity and leave cattle populations susceptible to new disease pathogens.
The purpose of this study was to estimate current levels of MHC class I diversity in the UK Holstein-Friesian dairy cattle population, primarily through the assessment of diversity in bull populations with genetic input into the UK herd. In a sample of Canadian Holstein bulls, levels of class I allelic diversity were low given the size of the population sampled, but no significant loss of diversity over a twenty year period of selection was detected.
Simulations of gene flow implicated trait selection as an influential force shaping diversity in the Canadian Holstein bull population. Haplotypes detected at high frequency were often negatively associated with selection traits indicating the action of heterozygote advantage. A SNP-based assay has been designed to facilitate rapid detection of common haplotypes and thus enable breeders to make more efficient selective breeding decisions whilst also maintaining MHC diversity in cattle populations.
Investigations of class I diversity were expanded to incorporate the British Friesian bull population which were shown to have a markedly different pattern of class I diversity to that observed in the Canadian Holstein sample. A number of novel allele sequences and haplotypes were detected in the British Friesian bulls, the characterisation of which has contributed to our knowledge of the mechanisms driving diversity in the cattle class I region.
MHC class I typing data from two bull populations and statistical analysis of trait associations with MHC haplotypes provides a comprehensive picture of MHC class I diversity in the wider UK herd and the selective forces integral to shaping diversity.
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