The challenges of genetic complexity - a study of Toll-like receptors in bovine mastitis
English language abstract Mastitis, which is defined as an inflammation of the mammary gland, is the most prevalent and costly disease in milk production. Improvement of disease management is important for the profitability in dairy industry, but in addition there are animal welfare issues as well as consumer interests. Mammary gland infections are most often caused by invasion and growth of bacteria and consequently an adequate immune function is essential for protecting the udder against infections. Even though incidence of mastitis strongly depends on both bacterial and environmental factors, genetic differences in the host immune system are considered to be a major aspect of individual susceptibility to mastitis.
Genetic variability of mastitis resistance is well established in dairy cattle. Currently, mastitis resistance is included in the Nordic breeding programs, and breeding values are calculated based on disease recordings in the National Health Recording systems. Due to low heritability, genetic improvement based on phenotypic selection has several limitations. Thus, implementation of genotypic information in future selection programs is considered to have promising applications. Although lines of evidence have suggested bovine mastitis susceptibility to be genetically controlled, the genes which regulate defence mechanisms are largely unknown. Exploiting genetic information require further knowledge of genetic variation. A common strategy to identify disease related genes is the analysis of candidate genes. Through the study of Toll-like receptors (TLRs), known to play an important role in the innate immune system, this thesis strives to reveal genetic variation and increase the insight of genes potentially involved in mastitis resistance.
In the first paper the bovine TLR6-TLR1-TLR10 gene cluster was characterized and genetic variation within the region that could be associated with mastitis susceptibility in the Norwegian Red (NR) cattle population was analysed. Furthermore, dense marker maps for the chromosomal regions surrounding TLR2 and TLR4 in Paper II enabled a study for potential disease association of these genes as well. In neither studies association between TLRs and mastitis resistance was found. The lack of association motivated the search for other possible candidate genes in Paper III. By expression profiling of several immune genes in cattle groups genetically different in mastitis susceptibility, relevant genes for further investigations was discovered.
