Linkage analysis was performed using 18 BXD (B=C57BL/6J, D=DBA/2J) recombinant inbred (RI) strains to identify QTLs associated with adenoviral LacZ expression, cytotoxic T-cell response, and cytokine production in response to infection with an adenoviralvector. Principal component analysis was used where PC1 is a composite of TNF-alpha, IL-6, IFN-gamma, and CTL phenotypes, and PC2 is a composite of LacZ and CTL phenotypes. A panel of 554 polymorphic markers was used in the genome scan.
This study confirmed a previously identified suggestive locus for TNF-alpha and IL-6 production at 42 cM on mouse Chromosome 9 (LRS=12.3) mapped by Zhang et al 2004 (J:86883). In the current study, Irav1 (immune response to adenovirus 1) was linked to PC1 at 41.01 cM near D9Mit289 and D9Mit26 (LRS=15.84). DBA/2J-derived alleles at Irav1 confer increased PC1 values with additive inheritance. A suggestive locus for PC1 mapped to 57.5 cM on mouse Chromosome 7 near D7Mit330 (LRS=9.42). C57BL/6J-derived alleles at D7Mit330 confer increased PC1 values with additive inheritance.
Suggestive linkage to PC2 mapped to 23 cM on mouse Chromosome 12 near D12Mit285 (LRS=13) and to 31 cM near D12Mit14 (LRS=12.7). C57BL/6J-derived alleles at these loci confer increased PC2 values with additive inheritance.
Suggestive linkage to PC2 mapped to 29.2 cM on mouse Chromosome 15 near D15Mit90 (LRS=9.41), 36 cM near D15mit29 (LRS=10.73), and 56.3 cM near D15Mit147 (LRS=11.75). C57BL/6J-derived alleles at D15Mit90 (29.2 cM) and D15Mit147 (56.3 cM) confer increased PC2 values whereas DBA/2J-derived alleles at D15Mit29 (36 cM) confer increased PC2 values. Zhang et al 2004 mapped a locus for LacZ expression to 42.8 cM and a locus for CTL expression to 61.7 cM but it is unclear if these are identical to D15Mit29 and D15Mit147, respectively, in the current study.