Towards the selection of chickens resistant to Salmonella and Campylobacter infections.

Resistance to infection with enteric pathogens such as Salmonella and Campylobacter can be at many levels and include both non-immune and immune mechanisms. Immune resistance mechanisms can be specific, at the level of the adaptive immune response, or non-specific, at the level of the innate immune response. Whilst we can extrapolate to some degree in birds from what is known about immune responses to these pathogens in mammals, chickens are not "feathered mice", but have a different repertoire of genes, molecules, cells and organs involved in their immune response compared to mammals. Fundamental work on the chicken's immune response to enteric pathogens is therefore still required. Our studies focus particularly on the innate immune response, as responses of heterophils (the avian neutrophil equivalent) from commercial birds, and macrophages from inbred lines of chickens, correlate with resistance or susceptibility to Salmonella infection with a variety of Salmonella serovars and infection models. We work on two basic resistance mechanisms - resistance to colonization with Salmonella or Campylobacter, and resistance to systemic salmonellosis (or fowl typhoid). To map genes involved in resistance to colonization with Salmonella and Campylobacter, we are using a combination of expression quantitative trait loci (eQTLs) from microarray studies, allied with whole genome SNP arrays (WGA), a candidate gene approach and analysis of copy number variation across the genome. For resistance to systemic salmonellosis, we have refined the location ofa novel resistance locus on Chromosome 5, designated SAL1, using high density SNP panels, combined with advanced back-crossing of resistant and susceptible lines. Using a 6th generation backcross mapping population we have confirmed and refined the SAL1 locus to 8-00 kb of Chromosome 5. This region spans 14 genes, including two very striking functional candidates; CD27-binding protein (Siva) and the RAC-alpha serine/threonine protein kinase homologue, AKT1.

Integrated immunogenomics in the chicken: deciphering the immune response to identify disease resistance genes.

Resistance to infection takes place at many levels, and involves both non-specific and specific immune mechanisms. The chicken has a different repertoire of immune genes, molecules, cells and organs compared to mammals. To understand the role of any disease resistance gene(s), it is therefore important to understand these different repertoires, and the bird's response to a particular pathogen. Our studies focus on the innate immune response, as responses of macrophages from inbred lines of chickens, and heterophils from commercial birds, correlate with resistance or susceptibility to Salmonella infection with a variety of Salmonella serovars and infection models. To map disease resistance genes, we are using a combination of expression quantitative trait loci (eQTLs) from microarray studies, allied with whole genome SNP arrays (WGA) and a candidate gene approach. There are over 500 human genes with the Gene Ontology term "innate immunity". We have identified over 400 of these genes in the chicken genome, and are actively identifying informative SNPs in them. The segregation of 6000 WGA SNPs across all of our inbred lines was also assessed, which should yield approximately 900 informative SNPs for a cross between any two lines. The initial focus of these studies is on mapping resistance genes in our inbred lines, but the studies will be extended to commercial flocks.