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Mapping of interactions and mouse congenic strains identified novel epistatic QTLs controlling the persistence of Salmonella Enteritidis in mice

Abstract

The host response to infection in humans is multifactorial and involves the complex interaction between two genomes (the host and the pathogen) and the environment. Using an experimental mouse model of chronic infection, we have previously identified the individual effect of three significant and one suggestive quantitative trait loci (QTLs) (Ses1, Ses2, Ses3 and Ses1.1) on Salmonella Enteritidis persistence in target organs of 129S6/SvEvTac mice. Congenic strain construction was performed by transferring each of these QTLs from C57BL/6J onto the 129S6/SvEvTac background, and phenotypic analysis confirmed that Ses1 and Ses1.1 contribute to bacterial clearance. Additional QTLs regulating Salmonella carriage in 129S6/SvEvTac mice were identified using a two-locus epistasis QTL linkage mapping approach conducted separately in females and males. The epistatic model for females included the individual effect of Ses3 and two significant interactions (Ses1D7Mit267 and Ses1DXMit48) accounting for 47% of the total phenotypic variance. The model for males included the individual effect of Ses1.1, three interactions (Ses1D9Mit218, D2Mit197D4Mit2 and D3Mit256D13Mit36) and explained 47% of the phenotypic variance. Our results suggest that the oligogenic nature of Salmonella persistence and epistasis are important constituents of the genetic architecture of the host response to chronic Salmonella infection.

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Acknowledgements

We thank Dr William Kay for providing S Enteritidis isolates and Rosalie Wilkinson and Line Larivière for their technical expertise. We also thank Dr Thomas Hudson, Dr Andrei Verner and Geneviève Geneau at the McGill University and Génome Québec Innovation Centre for their technical help and the use of their facility and equipment to perform the fluorescent genotyping work. We thank Dr Silvia Vidal for helpful discussions and critical review of the manuscript. This work was supported by grants from the Canadian Institutes of Health Research (CIHR), the Howard Hughes Medical Institute (HHMI, Infectious Diseases and Parasitology Program), the Canadian Genetic Diseases Network and the Mathematics of Information Technology and Complex System Network (Networks of Centres of Excellence Program). JC is the recipient of a CIHR fellowship. JCL-O is a CIHR Strategic Training Fellow in Infectious Diseases and Autoimmunity. DM is a scholar of CIHR and an International Research Scholar of the HHMI.

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Correspondence to D Malo.

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Caron, J., Loredo-Osti, J., Morgan, K. et al. Mapping of interactions and mouse congenic strains identified novel epistatic QTLs controlling the persistence of Salmonella Enteritidis in mice. Genes Immun 6, 500–508 (2005). https://doi.org/10.1038/sj.gene.6364234

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