Two-loci interaction confirms arthritis-regulating quantitative trait locus on rat chromosome 6.
A form of genetic interaction, or epistasis, occurs when one gene interferes with the phenotypic effect of another nonallelic gene. In pristane-induced arthritis (PIA) in rats we have previously identified Pia3, on chromosome 6, to be a locus that regulates onset of disease. In a single congenic strain containing Pia3 on the arthritis-susceptible DA background, DA.Pia3, no difference in onset of disease or early disease severity could be detected. After a two-loci interaction analysis of (E3 x DA)F2 intercross data, Pia3 was found to interact with Pia4 (chromosome 12). Subsequently, the DA.Pia3 congenic strain was combined with the DA.Pia4 congenic strain so that an effect of Pia3 could be observed. The effect of heterozygosity in Pia4 results in lower severity and thus in combination with Pia3 made it possible to observe that Pia3 alleles from the arthritis-resistant E3 strain rendered more severe arthritis into the otherwise 100% susceptible DA strain. As the introduction of Pia4 heterozygosity results in a lower level of arthritis severity we regard this as an additive interaction with a severity threshold-lowering effect.
Olofsson
Peter
P
Section for Medical Inflammation Research, Lund University, S-22184 Lund, Sweden.
Wernhoff
Patrik
P
Holmberg
Jens
J
Holmdahl
Rikard
R
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics*; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004195:Disease Models, Animal; D004843:Epistasis, Genetic; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D040641:Quantitative Trait Loci; D051381:Rats; D026801:Synteny; D013729:Terpenes
D013729:Terpenes; C009042:pristane