Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  7
• Reference
  J:316317 Souza SP, et al., Genetic mapping reveals Nfkbid as a central regulator of humoral immunity to Toxoplasma gondii. PLoS Pathog. 2021 Dec;17(12):e1010081
• ID
  MGI:7314942

Genes

Gene	Assay Type
Tpgi1	visible phenotype

Notes

• Experiment
  Protective immunity to parasitic infections has been difficult to elicit by vaccines. Among parasites that evade vaccine-induced immunity is Toxoplasma gondii, which causes lethal secondary infections in chronically infected mice. Here the auathors report that unlike susceptible C57BL/6J mice, A/J mice were highly resistant to secondary infection.
  
  The authors performed secondary infection experiments with the type I GT1 strain using 26 recombinant inbred (RI) mice. The AxB:BxA RI mouse panel contains an assortment of homozygous A/J and C57BL/6J alleles, which assist genetic mapping of loci that contribute to various phenotypes, including those related to T. gondii infection.
  
  Quantitative trait loci (QTL) analysis was performed with the package r/QTL in R (version 3.6.1). LOD scores for each marker were calculated using the Haley-Knott regression model with the function 'scanone', or for all possible combination of two markers (i.e. epistatic interactions) using the function 'scantwo'. 1000 permutations were performed to obtain the genome wide LOD threshold for a P value of <=0.05, which was considered statistically significant. Similar results were obtained with a linear mixed regression model. To estimate the effect each QTL had on the overall phenotype, the function 'fitqtl' was first used to fit the data to a multiple-QTL model. Statistical support was found for inclusion of all four QTL with LOD scores > 3 compared to any lesser combination of three-QTL (ANOVA P <0.02). Individual QTL effects were then calculated under the assumption of the four-QTL model, which collectively accounts for 91% of the observed phenotypic variance. No statistical support was found for epistatic interactions between QTL.
  
  Genetic mapping revealed four distinct QTL peaks with LOD scores greater than 3 (LOD scores inferred from Figure 2A; genome coordinates relative to GRCm39/mm39):
  
  Tpgi1 (Toxoplasma gondii immunity 1, secondary infection survival) maps to Chr 7: 30.3 - 33.0 Mb with a peak LOD score of ~3.5.
  
  Tpgi2 (Toxoplasma gondii immunity 2, secondary infection survival) maps to Chr 10 with a peak LOD score of ~6.5.
  
  Tpgi3 (Toxoplasma gondii immunity 3, secondary infection survival) maps to Chr 11 with a peak LOD score of ~3.4.
  
  Tpgi4 (Toxoplasma gondii immunity 4, secondary infection survival) maps to Chr 17 with a peak LOD score of ~3.5.
  
  None of the QTL bore evidence for epistatic interactions, and only the chromosome 10 QTL surpassed genome-wide permutation testing (n = 1000, P<0.05). Nevertheless, an additive-QTL model including all four QTL best fits the data compared to any lesser combination of them (P<0.02, ANOVA). The estimated effect on the phenotypic variance observed in the RI panel is 24%, 41%, 21% and 27% for the chromosome 7, 10, 11 and 17 QTL, respectively. Consistent with these estimates, complete phenotypic penetrance (i.e. allelic correlation at 100%) was not observed for any locus (Fig 2B). Moreover, replacing chromosomes 7 or 10 of C57BL/6J with those of A/J conferred no survival advantage to secondary infection in consomic mice.
  
  Nfkbid (MGI:3041243) is one of the most polymorphic genes within the Tpgi1 QTL region and sits between the genetic markers that flank the highest imputed LOD score.