Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  4
• Reference
  J:237153 Wisby L, et al., Spir2; a novel QTL on chromosome 4 contributes to susceptibility to pneumococcal infection in mice. BMC Genomics. 2013 Apr 11;14:242
• ID
  MGI:5904668

Genes

Gene	Assay Type
Spir2	resistance/susceptibility

Notes

• Experiment
  Linkage analysis was performed on 184 animals from a (BALB/cOlaHsd x CBA/CaOlaHsd)F2 intercross to identify QTLs associated with susceptibility to infection with the bacteria Streptococcous pneumoniae. Parental strain BALB/cOlaHsd is resistant to S. pneumoniae infection whereas parental strain CBA/CaOlaHsd is susceptible.
  
  Selective genotyping of (BALB/cOlaHsd x CBA/CaOlaHsd)F2 mice (CCBAF2), with phenotypes
  representing the extremes of the response after infection challenge, identified a novel region of significant linkage on Chromosome 4 contributing to susceptibility to pneumococcal disease. The QTL was named Spir2 (Streptococcus pneumoniae infection resistance 2).
  
  The peak of linkage was located at SNP 4_80 (rs4224562) at 82.5 Mb. The QTL location on
  chromosome 4, estimated by the one LOD support interval, was from SNP 4_47 (rs13477699) at 50.7 Mb to SNP 4_87 (rs3022987) at 88.2 Mb and was ~ 38 Mb in size. The LOD score for the peak of linkage exceeded the genome wide significance threshold of 3.10 with a LOD score of 4.56 for survival and 4.25 for bacteraemia. The QTL identified on chromosome 4 was estimated to account for 8% of the phenotypic variance.
  
  Congenic breeding was used to replicate detection of the Spir2 locus and to assess its contribution to the infection phenotype. Incipient congenic strains consisting of different portions of the chromosome 4 QTL from BALB/cByJ on a CBA/CaH background, and vice versa, were produced using a marker-assisted breeding. Mice that were heterozygous at the peak SNP (rs4224562) had both significantly longer survival times and lower levels of bacteraemia, following intranasal infection, when compared with homozygous animals. Infection challenges of the Chr4 incipient congenic strains confirmed detection of the Spir2 QTL observed in the CCBAF2 mice, but did not reduce the size of the critical region.
  
  The Spir2 locus region contains 169 genes, according to Ensembl V.65. One strong candidate gene, based on its known role in regulating innate immunity, is Tlr, but non-synonymous differences in the sequence of Tlr4 between BALB/cOlaHsd and CBA/CaOlaHsd were found to be common to other inbred strains, making it less likely to play a role in the Spir2 locus.