Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  12
• Reference
  J:310769 Pattaradilokrat S, et al., Plasmodium genetic loci linked to host cytokine and chemokine responses. Genes Immun. 2014 Apr-May;15(3):145-52
• ID
  MGI:6864504

Genes

Gene	Assay Type
Cxcl1lq	visible phenotype
Fgf2lq	visible phenotype

Notes

• Experiment
  Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate the effects of parasite factors on host immune responses and pathogenesis, the authors measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites.
  
  To identify genetic loci linked to the CC responses, the authors performed quantitative trait loci (QTL) analysis using genome-wide genotypes previously collected from 486 MSs34 and the CC measurements from the 22 progeny. An inoculum containing appropriate numbers of iRBC suspended in 100 ml of phosphate-buffered saline, pH 7.4, from donor mice was injected intravenously into experimental C57BL/6 mice or knock-out mice with the same genetic background.
  
  QTL mapping was performed using R/qtl library in the R2.12.2 software (http://www.rqtl.org/)53 as described previously. Briefly, day 5 parasitemia and day 4 CC levels from the progeny of the N67 x 17XNL cross were natural-log transformed to obtain normally distributed data sets before QTL analysis. A 5% threshold (P = 0.05) on the basis of 1000 permutations using standard interval mapping (EM method) was used as the significant cutoff level. A single-QTL genome scan was performed initially, followed by two-dimensional and finally two-QTL genome scans.
  
  Nine significant QTL were identified (genome coordinates relative to GRCm38/mm10):
  
  D5para1 (parasitemia on day 5 of infection 1) maps to Chr 10 with a peak LOD score of 3.2 at 10.7 cM.
  
  D5para2 (parasitemia on day 5 of infection 2) maps to Chr 13 with a peak LOD score of 3.3 at 19.4 cM.
  
  Cxcl10lq1 (CXCL10 level during Plasmodium yoelii infection 1) maps to Chr 7 with a peak LOD score of 2.8 at 20 cM.
  
  Cxcl10lq2 (CXCL10 level during Plasmodium yoelii infection 2) maps to Chr 13 with a peak LOD score of 2.8 at 19.4 cM.
  
  Il10lq1 (IL10 level during Plasmodium yoelii infection 1) maps to Chr 9 with a peak LOD score of 2.9 at 30.6 cM.
  
  Il1blq2 (IL1B level during Plasmodium yoelii infection 2) maps to Chr 13 with a peak LOD score of 3.1 at 19.4 cM.
  
  Il5lq1 (IL5 level during Plasmodium yoelii infection 1) maps to Chr 7 with a peak LOD score of 3.2 at 20 cM.
  
  Cxcl1lq (CXCL1 level during Plasmodium yoelii infection) maps to Chr 12 with a peak LOD score of 2.9 at 19.6 cM.
  
  Fgf2lq (FGF2 level during Plasmodium yoelii infection) maps to Chr 12 with a peak LOD score of 3.0 at 19.6 cM.
  
  The loci on chromosomes 7 and 13 had significant (P < 0.005) additive effects on IL-1-Beta, IL-5 and IP-10 responses, and the chromosome 9 and 12 loci had significant (P = 0.017) interaction.
  
  Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality.