Genetic control of chicken heterophil function in advanced intercross lines: associations with novel and with known Salmonella resistance loci and a likely mechanism for cell death in extracellular trap production

Abstract

Heterophils, the avian polymorphonuclear leukocyte and the counterpart of mammalian neutrophils, generate the primary innate response to pathogens in chickens. Heterophil performance against pathogens is associated with host disease resistance, and heterophil gene expression and function are under genetic control. To characterize the genomic basis of heterophil function, heterophils from F13 advanced intercross chicken lines (broiler × Leghorn and broiler × Fayoumi) were assayed for phagocytosis and killing of Salmonella enteritidis, oxidative burst, and extracellular trap production. A whole-genome association analysis of single nucleotide polymorphisms at 57,636 loci identified genomic locations controlling these functional phenotypes. Genomic analysis revealed a significant association of extracellular trap production with the SAL1 locus and the SLC11A1 gene, which have both been previously associated with resistance to S. enteritidis. Fine mapping supports SIVA1 as a candidate gene controlling SAL1-mediated resistance and indicates that the proposed cell-death mechanism associated with extracellular trap production, ETosis, likely functions through the CD27/Siva-1-mediated apoptotic pathway. The SLC11A1 gene was also associated with phagocytosis of S. enteritidis, suggesting that the Slc11a1 protein may play an additional role in immune response beyond depleting metal ions to inhibit intracellular bacterial growth. A region of chromosome 6 with no characterized genes was also associated with extracellular trap production. Further characterization of these novel genes in chickens and other species is needed to understand their role in polymorphonuclear leukocyte function and host resistance to disease.

Fine mapping of complex traits in non-model species: using next generation sequencing and advanced intercross lines in Japanese quail

“…We suspected this result was the consequence of a lower detection power because the origin of alleles was not accounted for. Indeed, recent AIL studies included genotyping and phenotyping of all individuals in the AIL line [56], or were set up from at least one inbred line [57], which made it possible to trace the origin of alleles back to the F0 lines. To overcome the problem, an association analysis was performed in our AIL, with the assumption that enough power would be gained by adding information from dams within families of sires homozygous for the QTL, that were uninformative in the QTL mapping analysis based on familial linkage.…”

Impacts of Salmonella enteritidis infection on liver transcriptome in broilers

“…The action of tagging proteins for proteolysis with ubiquitin is directly related to inflammation, apoptosis, and the immune response to S. enteritidis (Te Pas et al, 2012). When regulated, the programmed death of infected cells and the degrading action of ubiquitin-specific peptidases facilitate the clearance of systemic Salmonella infection (Jiang and Zhijian, 2012;Redmond et al, 2011). Excessive inflammatory actions, however, can result in epithelial damage that enhances the ability of Salmonella to further invade the area of infection (Kum et al, 2011).…”

Integrated Genomic Approaches to Enhance Genetic Resistance in Chickens

“…Subsequent fine-mapping of the SAL1 region revealed two strong functional candidates for Salmonella response: AKT1 (protein kinase B, or PKB) and CD27 binding protein (SIVA) (76). Fine-mapping of heterophil functional response to Salmonella in a highly advanced intercross strongly supported the SAL1 QTL position containing AKT1 and SIVA and suggested heterophil function as a specific mechanism to explain the host-resistance properties that map to this region (110).…”