Stsl1^CAST/EiJ
QTL Variant Detail

Summary

• QTL variant: Stsl1^CAST/EiJ
• Name: Salmonella typhimurium susceptibility locus 1; CAST/EiJ
• MGI ID: MGI:6324065
• QTL: Stsl1 Location: Chr8:11350000-17050016 bp Genetic Position: Chr8, Syntenic

Variant origin

• Strain of Specimen: CAST/EiJ

Variant description

• Allele Type: QTL
• Inheritance: Not Specified

Notes

Mapping and Phenotype information for this QTL, its variants and associated markers

J:261997

QTL Reference Notes

The Collaborative Cross (CC) is a large (~1,000 line) panel of recombinant inbred (RI) mouse strains being developed through a community effort (Churchill et al. 2004). The CC combines the genomes of eight genetically diverse founder strains - A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ - to capture nearly 90% of the known variation present in laboratory mice. CC strains are derived using a unique funnel breeding scheme. Once inbred, the RI CC lines can be used to generate thousands of potential 'outbred' but completely reproducible genomes through the generation of recombinant inbred crosses (RIX). The designation 'PreCC' is used to describe a mapping population of CC mice that is still at incipient stages of inbreeding. CTC (2004), Churchill, G. A., et al.. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet. 36, 1133-7.

Salmonella is a Gram-negative bacterium causing a wide range of clinical syndromes ranging from typhoid fever to diarrheic disease. Non-typhoidal Salmonella (NTS) serovars infect humans and animals, causing an important health burden in the world. In this study, the authors investigated the host response to S. Typhimurium infection in 35 Collaborative Cross (CC) strains.

CC mice were purchased from the Systems Genetics Core Facility at the University of North Carolina (UNC), previously generated and bred at Tel Aviv University in Israel, Geniad in Australia, and Oak Ridge National Laboratory in the US, and further bred and maintained at the Institut Pasteur under specific-pathogen-free (SPF) conditions. 129S2/SvPasCrl and C57BL/6J SPF mice were obtained from Charles River France and used as resistant (low bacterial loads in target organs) and susceptible (high bacterial loads) controls, respectively.

One hundred and forty-eight mice from 35 CC strains were challenged intravenously with 1000 colony-forming units (CFUs) of S. Typhimurium. Bacterial load was measured in spleen and liver at day 4 post-infection. The authors identified one strain, CC042/GeniUnc, as highly susceptible to S. Typhimurium infection.

CC strains were genotyped previously at Wellcome Trust Centre for Human Genetics (Oxford, UK) and at UNC (Chapel Hill, USA) with several high-density arrays, including Mouse Universal Genotyping Array (MUGA and MEGA-MUGA) containing respectively 7.5 and 77.8 K SNPs and Mouse Diversity Array (MDA) containing 620 K SNPs. All the polymorphic SNPs homozygous in all founder strains were selected and introduced in HAPPY format using build 37 of the mouse reference genome. Each CC genome was reconstructed as a haplotype mosaic using a Hidden Markov Model (HMM) in HAPPY software to estimate the probabilities of descent from each founder strain at each locus.

QTL mapping was performed under R statistical software (release version 3.2.0) with the happy.hbrem package. Founder contributions for each trait analyzed were determined by hierarchical Bayesian random-effects model using the happy.hbrem package.

Six QTL were mapped at genome-wide significance:

QTL Stsl1 (Salmonella Typhimurium susceptibility locus 1) is significant for spleen bacterial load and maps to Chr 8: 11.3 - 17.0 Mb with a peak LOD score of 4.7 at 12.5 Mb. The founder contributions, calculated across the critical interval and at the peak location, indicates a contrast between PWK/PhJ (higher spleen bacterial loads) versus 129S1/SvImJ and CAST/EiJ strains (lower values) at Stsl1.

QTL Stsl2 (Salmonella Typhimurium susceptibility locus 2) is significant for spleen bacterial load and maps to Chr 10: 46.4 - 54.0 Mb with a peak LOD score of 3.8 at 52.3 Mb. The founder contribution indicates a contrast between PWK/PhJ and C57BL/6J (higher) versus NZO/HlLtJ (lower) at Stsl2.

QTL Stsl3a (Salmonella Typhimurium susceptibility locus 3a) is significant for spleen bacterial load and maps to Chr 1: 77.5 - 95.9 Mb with a peak LOD score of 3.3 at 83.9 Mb. For Stsl3a, founder contribution indicates a contrast between C57BL/6J (higher) versus the others.

QTL Stsl3b (Salmonella Typhimurium susceptibility locus 3b) is significant for spleen bacterial load and maps to Chr 1: 74.1 - 81.8 Mb with a peak LOD score of 3.0 at 79.2 Mb. For Stsl3b, founder contribution indicates a contrast between 129S1/SvImJ and C57BL/6J (higher) versus PWK/PhJ (lower).

QTL Stsl4 (Salmonella Typhimurium susceptibility locus 4) is significant for liver bacterial load and maps to Chr 6: 77.1 - 90.0 Mb with a peak LOD score of 3.2 at 81.2 Mb. The founder contribution is a contrast between NZO/HlLtJ and PWK/PhJ (higher) versus C57BL/6J (lower) at Stsl4.

QTL Stsl5 (Salmonella Typhimurium susceptibility locus 5) is significant for liver bacterial load and maps to Chr 17: 80.5 - 91.1 Mb with a peak LOD score of 3.1 at 84.8 Mb. The founder contribution mainly shows a contrast between C57BL/6J (higher) versus NOD/ShiLtJ (lower) at Stsl5.

References

• Original: J:261997 Zhang J, et al., Identification of new loci involved in the host susceptibility to Salmonella Typhimurium in collaborative cross mice. BMC Genomics. 2018 Apr 27;19(1):303
• All: 1 reference(s)