Experiment
The inheritance and complexity of the C5-independent genetic control to C. albicans resistance of AKR/J mice was investigated by phenotyping mice from an F2 cross generated between resistant AKR/J and susceptible A/J progenitors, in which all mice were fixed for C5 deficiency.
A total of 158 [A/J x AKR/J]F2 mice were infected with C. albicans blastospores. The kidney fungal burden was determined and used as a quantitative phenotypic measure of susceptibility in linkage analysis. F2 mice were genotyped with a custom panel of 257 informative, polymorphic markers distributed across the genome.
The analysis identified a significant locus, Carg3, Candida albicans resistance gene 3, contributing to resistance to C. albicans in the AKR/J strain that mapped to chromosome 8 (LOD=3.95, P<0.05) with the 95% confidence interval between 53.6-96.9 Mb, peak at 75.0 Mb, (peak SNP:rs3722665). Authors consider 4 genes as priority candidate genes for Carg3: Adcy7, Dnaja2, Gab1 and Inpp4b.
A two-dimensional Haley-Knott multiple regression anaylsis revealed that the joint effect of Carg3 and Carg4 increased the LOD score to 11.5, suggesting an additive effect which explains 28% of the phenotypic variance observed.
Analysis Tools