Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  9
• Reference
  J:186009 Pelletier AN, et al., The size of the plasmacytoid dendritic cell compartment is a multigenic trait dominated by a locus on mouse chromosome 7. J Immunol. 2012 Jun 1;188(11):5561-70
• ID
  MGI:5780193

Genes

Gene
Pdcc3

Notes

• Experiment
  The primary function of pDC (plasmacytoid dendritic cells) is to potently produce type 1 IFNs upon stimulation, which is highly relevant in antiviral responses. Identifying the genetic loci affecting the size of the pDC compartment, defined by both the proportion and absolute number of pDC in the spleen was the focus of this study.
  
  The proportion of pDC in the spleen was obtained from 5 inbred strains. C57BL/6 exhibited the lowest proportion and number of pDC; whereas NOD and NOR mouse strains exhibited the highest of the strains tested. To enhance the detection of pDC differences the proportions of pDC in B6 and NOD with a null mutation for Rag was examined. The Rag deficient background presented a difference of 8% in pDC proportion in B6.129S7-Rag1tm1Mom/J and NOD.129S7(B6)-Rag1^tm1Mom/J mice, respectively. Correspondingly, the absolute number of pDC in the spleen was lower in B6.129S7-Rag1tm1Mom/J mice relative to NOD.129S7(B6)-Rag1^tm1Mom/J.
  
  A cohort of 181 (B6.129S7-Rag1tm1Mom/J x NOD.129S7(B6)-Rag1^tm1Mom/J)F2 mice were generated. Genome wide SNP genotyping was performed on the F2 mice. Linkage analysis for pDC proportion demonstrated significant linkage on Chromosome 7 with a LOD=5.46. In addition, linkage above the suggestive threshold was observed on Chromosomes 8 and 13.
  
  Linkage analysis was also performed on the absolute number of pDC in the spleen of the F2 mice to fully characterize the loci defining the size of the pCD compartment. Significant linkage was detected at the same locus as pDC proportion on Chr 7. Linkage above the suggestive threshold on Chrs 1 and 16 were also observed, yet Chrs 8 and 13 were not linked to the absolute number of pDC.
  
  Higher-resolution maps of Chromosome 7 for linkage to both proportion and absolute number of pDC further delimited the locus, named Pdcc1 (plasmacytoid dentritic cell compartment 1) to the proximal end of chromosome 7, peaking at SNP rs3670807 at 47.4 Mb. The 95% confidence interval mapped between 23.5 and 63.5 Mb. Mice harboring the NOD/NOD genotype at SNP rs3670807 exhibited a higher proportion and absolute number of pDC relative to heterozygotes at the same locus, which exhibited higher levels of pDC compared with B6 homozygotes.
  
  In joint LOD score analysis significant genetic interactions were detected between Pdcc1 (rs3670807) and Pdcc2 on Chromosome 11 at rs1341088 that linked to the proportion of pDC, LOD=9.53 [Fig 5]. Mice that were homozygous for NOD at both SNPs exhibited the highest proportion of of pDC. The lowest proportion was found in mice that were B6 homozygous at the Chr 7 SNP, but NOD homozygous at the Chr 11 SNP.
  
  Similarly, segregation of the F2 mice according to their genotype at the two SNPs defining the peak joint LOD score at Pdcc1 (rs3670807) and Pdcc3 on Chr 9 at rs3665206 for the absolute number of pDC demonstrates a significant, complex interaction, LOD=9.60 [Fig 5.].
  
  Candidate genes for Pdcc1, Pdcc2, and Pdcc3 remain to be defined.