Immunogenetics in dairy cattle : somatic cell count and natural antibody levels

There remains is a lot to be learned about the interpretation of genetic parameters and the biology of disease resistance and SCS. This PhD thesis aimed to obtain additional insight in disease resistance and SCS by: 1) quantifying the impact of genetics on innate immunity, represented by natural antibodies (NAb), through estimation of heritabilities and genetic correlations; 2) identifying the genomic regions involved in SCS and NAb levels; 3) quantifying the impact of genetics on environmental sensitivity for SCS. Natural antibody levels are heritable with heritabilities ranging from 0.06 to 0.55 and in general, heritabilities for NAb isotypes were higher than heritabilities for total NAb levels, the latter making no distinction between isotypes. Genetic correlations suggest that isotypes IgA and IgM have a common genetic basis, but that the genetic basis for IgG1 differs from that for IgA or IgM. An additional genome-wide association study for NAb levels showed that information can be gained when total NAb levels are further subdivided into isotype levels. A region on chromosome 23 was significantly associated with genetic variation in isotype IgM levels. The bovine major histocompatibility complex (MHC) is located near this region, making this a region of candidate gene(s) involved in NAb expression in dairy cows both from a functional and positional perspective. Results from the study on genetic parameters and the genome-wide association study suggest that NAb isotypes may provide a better characterization of different elements of the immune response or immune competence and enable more effective decisions when breeding programs start to include innate immune parameters. A genome-wide association study was not only performed for NAb levels, but also for SCS. Relatively few associations, however, were found, which suggests that SCS is controlled by multiple loci, each with a relatively small effect, distributed across the genome. Somatic cell score is partly under genetic control, but is also affected by the environment. Sensitivity to respond to environmental factors, however, can have a genetic origin. Environmental factors can be divided into known and unknown factors, referred to as macro- and micro environment, respectively. Macro-environmental sensitivity can be expressed as genetic variation in the slope of a reaction norm, whereas micro-environmental sensitivity can be expressed as differences in residual variance that have a genetic origin. Both macro- and micro-environmental sensitivity were found for SCS and these sensitivities were positively correlated. Knowledge on both forms of sensitivity can aid in optimization of selection as correlations between the additive genetic variance in intercept, slope and environmental variance were all away from unity. Selection for reduced environmental sensitivity has the potential to reduce variability in animal performance due to environmental factors and herewith increase predictability of performance across and within environments. Knowledge on disease biology is important to fully understand the processes involved when selecting for increased disease resistance, as a better understanding enables a better prediction of the consequences. In this context, the general discussion involved the phenotype definition and statistical modeling, influence of maternal effects and genetic variation in the MHC region. The discussion contained three conclusions: 1) analyses of cell types (detailed phenotypes) rather than SCS can provide further insight in the genetic control of SCS and mastitis; 2) no evidence was found for maternal genetic effects on NAb levels in milk. Maternal environmental effects, however, could play a role in NAb levels; 3) genetic diversity in the MHC region is maintained by natural selection. Selective breeding and farm management practices may affect this genetic diversity, which could bring about negative effects on animal fitness, such as fertility problems. Selective breeding for specific MHC haplotypes may therefore impose a risk for negative effects on animal health