Mapping Data

Experiment

• Experiment
  TEXT-Congenic
• Chromosome
  12
• Reference
  J:218990 Kanagaratham C, et al., Mapping of a chromosome 12 region associated with airway hyperresponsiveness in a recombinant congenic mouse strain and selection of potential candidate genes by expression and sequence variation analyses. PLoS One. 2014;9(8):e104234
• ID
  MGI:5829088

Genes

Gene
Ahrq1
D12Mit285
D12Mit52
D12Mit158

Notes

• Experiment
  This study reports QTL mapping results using a unique inbred strain generated as part of an AcB/BcA recombinant congenic panel. In a previous study of airway responsiveness (J:156885) recombinant congenic strain BcA86 was noted as most significantly different from its major genetic donor strain, C57BL/6J, and resembled the A/J phenotype. The A/J strain has an airway hyperresponsive phenotype when exposed to methacholine; C57BL/6J mice are relatively less responsive to the same exposure.
  
  To identify genetic determinants of airway responsiveness in the BcA86 strain, BcA86 mice were backcrossed to C57BL/6J to generate F1 mice. The resulting progeny were subsequently interbred to generate 205 F2 mice for QTL mapping.
  
  Penh, a dimensionless index of airway obstruction was measured using an unrestrained whole body plethysmograph in response to varied doses of methacholine prepared in PBS. BcA86F2 mice were genotyped in recombinant regions of BcA86 with 41 microsatellites and 47 SNP markers, with an average spacing of 3.5 Mbp between markers. To determine which markers were significant, 10,000 permutations of randomized genotype-phenotype combinations from the data were generated to obtain a LOD threshold. Association between marker genotype and phenotype was determined using R/QTL library and by standard interval mapping to obtain LOD scores for each marker.
  
  Of the 88 markers, nine consecutive markers on Chromosome 12 were significantly associated with the airway hyperresponsive (AHR) phenotype. QTL Ahrq1, airway hyperresponsive QTL 1, spanned a 95% confidence interval between markers D12Mit285 (54.6 Mbp) and D12Mit158 (82.6 Mbp). The most significant marker among the 8 was D12Mit52 at 77.0 Mbp with a LOD score of 5.11, p0.00368. The QTL explained 12.5% of the phenotypic variance in BcA86F2 mice. The distribution of phenotypes, among the possible genotypes, at D12Mit52 revealed that the mean log2(Penh) of animals with homozygous or heterozygous A/J genotype was significantly higher than those with homozygous B6 genotypes.
  
  Based on analyses of expression differences and of nsSNPs, Foxa1, Vcpkmt and Snapc1 were selected as potential candidate genes for Ahrq1.