Faraday earmarked proposal: Genomic approaches to improving pig innate and adaptive immunity and health.
Lead Research Organisation:
University of Edinburgh
Department Name: The Roslin Institute
Abstract
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Technical Summary
Understanding the genetic control of innate immunity in domestic animals is both of fundamental scientific interest and strategically important. By means of a genome scan in pigs by linkage disequilibrium for traits of innate immunity, experiments targeted at unravelling the genetic factors determining the appropriate maturation of the gastrointestinal mucosal immune system, and comparative genomics taking advantage of the annotated human and murine genome sequence we will contribute to the understanding of the genetic control of immune traits and define genetic markers for use in practical breeding situations. Our genome scan will consist of a panel of 1500 SNP markers, tested on c. 600 pigs, associated by TDT LD tests with a wide range of innate immune measures. Innate (and adaptive) immune traits will include white blood cell counts, acute phase proteins, and mononuclear cell subset phenotypes. Confirmation will be performed on pigs measured for the same immune measures under lower health conditions. Maturation of the mucosal immune system will be contrasted sequentially across time between distinct pig genotypes, concentrating on antigen presenting cell (APC) populations in the intestinal mucosa as the major intersection point between innate and adaptive immune systems. Additionally, dietary manipulation will be used to determine immune response to pathogens and tolerance to food antigens (serum anti-soya IgG1 and IgG2 levels) and commensal microorganisms post-weaning. Genetic influences on immune maturation, comparative genomics and knowledge of the physical location of linked genes will give considerable insight into genes influencing innate immunity. This will lead to the development of tools for use by breeders under practical situations, particularly, genetic markers measurable under high-health conditions that are predictive of immunity and performance under lower health conditions. Joint with BB/C510432/1
Organisations
Publications
Clapperton M
(2009)
Traits associated with innate and adaptive immunity in pigs: heritability and associations with performance under different health status conditions.
in Genetics, selection, evolution : GSE
Clapperton M
(2008)
Pig peripheral blood mononuclear leucocyte subsets are heritable and genetically correlated with performance.
in Animal : an international journal of animal bioscience
Clapperton, M
(2008)
Pig peripheral blood CD11R1+ mononuclear leukocytes - characterization, heritibility and correlations with performance
in 3rd International Symposium on Animal Functional Genomics (ISAFG)
Clapperton, M
(2008)
Characterization, heritability and correlations with performance
in EADGENE
Clapperton, M
(2009)
Use of SNP association analysis to detect regions on the pig genome associated with immune traits
in Pig Genome III Conference: A celebration for completing the pig genome sequence. Swine Genome Sequencing Consortium and PigNet Genome Conference.
Glass, E
(2009)
Approaches to filling that Phenotype Gap
in EADGENE
| Description | 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. |
| Exploitation Route | These research findings have formed the basis of two further large scale research programmes: 1. A research programme at INRA in France, based on this project, that looks further into the genetic control of the heritable traits we measured 2. A research and development programme in Canada, led by industry, that is actively looking at the practical utilisation of our findings under field conditions |
| Sectors | Agriculture, Food and Drink |
| Description | These research findings have formed the basis of two further large scale research programmes: 1. A research programme at INRA in France, based on this project, that looks further into the genetic control of the heritable traits we measured 2. A research and development programme in Canada, led by industry, that is actively looking at the practical utilisation of our findings under field conditions |
| First Year Of Impact | 2010 |
| Sector | Agriculture, Food and Drink |
| Impact Types | Economic |