Ses1a^C57BL/6J
QTL Variant Detail

Summary

• QTL variant: Ses1a^C57BL/6J
• Name: salmonella enteritidis susceptibility 1a; C57BL/6J
• MGI ID: MGI:2668905
• QTL: Ses1a Location: Chr1:73726922-73727077 bp Genetic Position: Chr1, Syntenic

Variant origin

• Strain of Specimen: C57BL/6J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers resistance to Salmonella enteritidis infection compared to 129/Sv. (J:81412)
• Inheritance: Recessive

Notes

In female animals, Ses1a shows interaction with Ses4 and Ses5. Female animals homozygous for C57BL/6J-derived alleles at both Ses1a and Ses4, or at both Ses1a and Ses5, show significant reduction in Salmonella bacterial load (~15-fold reduction) compared to female animals homozygous at Ses1a only.

In male animals, Ses1a shows interaction with Ses6. Male animals homozygous for C57BL/6J-derived alleles at both Ses1a and Ses6 exhibit significant reduction in Salmonella bacterial loads.

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

J:81412

Genome scan using 80 polymorphic markers at an average spacing of 20 cM was performed on a population of (C57BL/6J x 129/Sv)F2 animals to identify QTLs associated with resistance to Salmonella enteritidis infection. Parental strain C57BL/6J is resistant to S.enteritidis and clears an infection by 42 days post-innoculation while parental strain 129/Sv is susceptible and cannot clear an infection after 42 days. Three major QTLs named Ses1, Ses2, and Ses3 were mapped to chromosomes 1, 7, and 15, respectively. Together these QTLs explain 32% of the phenotypic variance.

Ses1 maps to 48.7 cM on mouse Chromosome 1 with a peak LOD score = 9.9 at D1Mcg5. Ses1 spans 23.1 cM and explains 14% of the phenotypic variance. Ses2 maps to 33.3 cM on mouse Chromosome 7 with a peak LOD score = 4 at D7Mit62. Ses2 spans 29.1 cM and explains 6% of the genetic variance. Ses3 maps to 38.8 cM on mouse Chromosome 15 with a peak LOD score = 3.2 at D15Mit29. Ses3 spans 20.6 cM and explains 4% of the phenotypic variance.

C57BL/6J-derived alleles confer recessively inherited resistance to S. enteritidis infection at all 3 QTLs. Linkage to S.enteritidis resistance shows greater significance in female animals at all loci.

Slc11a1 (Nramp1) contains a functional polymorphism (Asp169)in C57BL/6J and is a possible candidate gene for Ses1. The C57BL/6J allele is a null allele and is linked to susceptibility to Salmonella typhimurium infection. 129/Sv animals carrying the Asp169 allele exhibit lower S. enteritidis CFU counts compared to129/Sv animals. Thus, Slc11a1 is a viable candidate gene and may play a role in bacterial clearance.

J:100367

Congenic lines were created to evaluate previously identified Salmonella susceptibility loci Ses1 (chr1), Ses2 (chr7), and Ses3 (chr15). Authors indicate that Ses1 is composed of 2 different linked loci, Ses1a (a.k.a. Ses1) and Ses1b (a.k.a. Ses1.1). Donor DNA from resistant strain C57BL/6J was introgressed onto the genetic background of susceptible strain 129S6/SvEvTac for each QTL. The effects of Ses1a (48.7 cM) and Ses1b (21 cM) on mouse Chromosome 1 were detected in the congenic lines. 129.B6-Ses1a and 129.B6-Ses1b lines cleared Salmonella infection significantly better than background strain 129S6/SvEvTac. The effects of Ses2 and Ses3 were not observed in the congenics.

A population of 300 (C57BL/6J x 129S6/SvEvTac)F2 animals were used to create a high density linkage map for linkage analysis. 244 microsatellite markers at an average spacing of 10.7 cM and 3 SNP markers were used for the genome scan. Ratio transmission distortion (RTD) was observed in a 40.7 cM interval on mouse Chromosome 7 between D7Mit228 and D7Mit237, which includes the Ses2 locus. The RTD region had a significantly high incidence of the homozygous C57BL/6J genotype (39%-41%) in female F2 mice compared to the expected incidence of 25%.

Ses1a was detected in a single-point linkage analysis. In female animals, Ses1a shows peak linkage at D1Mcg5 (39.3 cM; LOD=7.59) and in male animals Ses1a shows peak linkage at D1Mit19 (36.9 cM; LOD=4.4). C57BL/6J-derived alleles at Ses1a confer resistance to Salmonella infection with recessive inheritance.

Two-point linkage analysis detected several novel interacting loci involved in the clearance of Salmonella infection. These new QTL, Ses4-Ses10, are discussed below.

In female F2 animals, Ses1a shows significant interaction with Ses4 at 14.2 cM near DXMit48 on mouse Chromosome X and Ses5 at 11 cM near D7Mit267 on mouse Chromosome 7. Female animals homozygous for C57BL/6J-derived alleles at both Ses1a and Ses4, or at both Ses1a and Ses5, show significant reduction in Salmonella bacterial load (~15-fold reduction) compared to female animals homozygous at Ses1a only. Ses4 and Ses5 do not exert an effect without Ses1a. A small effect on mouse Chromosome 15 attributed to Ses3 was also detected in female F2 animals.

In male F2 animals, significant interaction was detected between Ses1a and Ses6 at 4 cM near D9Mit218 on mouse Chromosome 9. Interacting locus pairs were also detected between Ses7 on mouse Chromosome 2 (D2Mit192; 76.3 cM) and Ses8 on mouse Chromosome 4 (D4Mit2; 6.5 cM), and betweenSes9 on mouse Chromosome 3 (D3Mit256; 66.2 cM) and Ses10 on mouse Chromosome 13 (D13Mit36; 53 cM). C57BL/6J-derived alleles confer increased Salmonella clearance (reduced bacterial load) with recessive inheritance at all new male-specific loci, except atSes7 which shows dominant inheritance. A significant effect on Salmonella clearance in male F2 animals was detected on mouse Chromosome 1 and is attributed to Ses1b.

References

• Original: J:81412 Caron J, et al., Identification of genetic loci controlling bacterial clearance in experimental Salmonella enteritidis infection: an unexpected role of Nramp1 (Slc11a1) in the persistence of infection in mice. Genes Immun. 2002 Jun;3(4):196-204
• All: 2 reference(s)