Genomic approaches to improving pig innate and adaptive immunity and health

This project addressed the genetic control of adaptive and innate immunity in growing pigs, quantified the genetic control of such traits, showed their relationship to individual animal health and performance, and detected genetic markers that can potentially be used to breed animals for improved immunocompetence. The project objectives and achievements were:

Objective 1: To scan the genome for quantitative trait loci (QTL) controlling innate immunity traits, for pigs reared under specific pathogen-free conditions. This was completed, on a greater number of animals and a denser SNP array than initially envisaged. However, it should of course be noted that in the four years since the completion of this project genomic resources have moved on substantially and the pig genome sequence has become available. Hence, we regularly revisit and update the interpretation of our results.

Objective 2: To verify associations between SNP and immune/performance traits in a lower health status environment. Completed, as above.

Objective 3: To refine marker based predictors for generalised immunity through comparative physical genomic mapping. Completed, the efforts were put up front into the design of a more comprehensive and denser SNP chip than envisaged, rather than post hoc refining of mapped locations. The pig genome sequence has allowed us to further interpret our results, and our largest commercial partner has expressed a desire to re-evaluate our phenotypes using a denser SNP chip (unavailable at the time of the project).

Objective 4: To identify genetic factors that determine maturation of the gastrointestinal mucosal immune system. Completed, demonstrating that animal genotype for growth and performance traits alters the maturation of the GI mucosal immune system.

Objective 5: To identify genetic factors that influence immunity to pathogens, and tolerance to food antigens and commensal microorganisms in early life (post-weaning). Completed, although no effect of the pig genotypes studied were observed for tolerance to food antigens or primary and secondary responses to injected antigens.

Objective 6: To identify interactions between the innate immune profiles seen in blood with parameters of gut immunity and microbial diversity in the gut. Addressed, however the cells with the most marked effects in the gut lamina propria were at undetectable levels in the peripheral blood. Therefore, we were unable to identify interactions.

Objective 7: To relate immune traits and genetic markers to overall performance and health. Completed, consistent genetic relationships between immune traits and overall performance and health were observed, and genetic markers underlying these relationships were identified.

Improving animal health remains one of the most difficult challenges facing livestock production industries. In this project we address health in the growing pig and propose approaches to breed pigs that are (genetically) more likely to be healthy on commercial farms. In particular, we investigated traits that describe attributes of the innate and adaptive immune responses and (i) showed that they are moderately to strongly genetically controlled, (ii) showed that they are predictive of animal health and performance, and (iii) suggested the means by which pig breeding companies can include his information into their breeding programmes.

1. We performed the first genome scan by linkage disequilibrium in any livestock species for traits describing innate and adaptive immune response, using state-of-the-art medium-density SNP arrays. With stringent significance thresholds, several SNPs were declared significant for a variety of peripheral blood mononuclear leucocytes (PBML) and acute phase proteins (APP). Significant SNPs include expected results, e.g. SNPs within the MHC complex, as well as a number of novel associations.



2. We demonstrated strong genetic control of many immune traits, including PBML and APP, with heritabilities of these traits often being as high as 0.5. These traits were strongly heritable, irrespective of the farm health status.



3. We detected and confirmed significant genetic relationships between components of the immune response and animal performance and health. In particular, peripheral NK cells numbers were invariably negatively correlated with animal performance, suggesting they diagnose underlying health problems. As well as being of applied interest, this finding opens up new research possibilities.



4. We detected highly significant genetic effects for mucosal immune development in the pig intestinal lamina propria. Accompanying this, we demonstrated that genetic differences in mucosal immune development had no effect on the development of oral tolerance.



5. We demonstrated regional differences (within small intestine) in the rate of development of the mucosal immune system.



6. We disentangled maternal and animal genetic effects for postweaning response to dietary antigens, and demonstrated strong maternal effects for all the IgG measurements performed.



7. We identified several highly significant SNPs that contribute to between-animal differences in postweaning response to dietary antigens.