Experiment
To identify collagen-induced arthritis susceptibility loci outside of the MHC, crosses between the DBA/1 and the less susceptible B10.Q strain were analyzed. Analysis of 224 (B10.Q x DBA/1)F2 intercross mice identified a locus, D6Mit19, with a LOD score of 4.7 [chi square = 10.42 with 2df (p = 0.0055)] associated with the arthritis onset trait explaining ~16% of the genetic variance. Figure 2 displays QTL as mapping between D6Mit9 and D6Mit86.
The disease promoting allele was dominantly inherited from the B10.Q strain, because a delayed onset of disease was associated with the DBA/1 allele in a recessive manner.
Analysis of 86 [(B10.Q x DBA/1)F1 x B10.Q]F2 backcross mice confirmed the existence of the Cia6 QTL. Most significant association was with the D6Mit188 marker (Z = 2.7, chi square = 8.01, p = 0.0047).
F2 backcross mice heterozygous for relevant markers on Chromosome 6 were mated with B10.Q mice. Genotype analysis of 132 N3 backcross mice showed association of the onset trait with D6Mit124 (Z=2.5, p = 0.0092). Putative candidate genes in the region include the Igk gene family, Il12a, Il17r, Il5a and the Tcrb gene family.
Analysis Tools