title: High-resolution mapping of a complex disease, a model for rheumatoid arthritis, using heterogeneous stock mice.
abstract: Resolving the genetic basis of complex diseases like rheumatoid arthritis will require knowledge of the corresponding diseases in experimental animals to enable translational functional studies. Mapping of quantitative trait loci in mouse models of arthritis, such as collagen-induced arthritis (CIA), using F(2) crosses has been successful, but can resolve loci only to large chromosomal regions. Using an inbred-outbred cross design, we identified and fine-mapped CIA loci on a genome-wide scale. Heterogeneous stock mice were first intercrossed with an inbred strain, B10.Q, to introduce an arthritis permitting MHCII haplotype. Homozygous H2(q) mice were then selected to set up an F(3) generation with fixed major histocompatibility complex that was used for arthritis experiments. We identified 26 loci, 18 of which are novel, controlling arthritis traits such as incidence of disease, severity and time of onset and fine-mapped a number of previously mapped loci.
authors.affiliation: Division of Medical Inflammation Research, Department of Medical Biochemistry, Biophysics Karolinska Institute, 17177 Stockholm, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Ahlqvist
authors.forename: Diana
authors.initials: D
authors.lastname: Ekman
authors.forename: Therese
authors.initials: T
authors.lastname: Lindvall
authors.forename: Marjan
authors.initials: M
authors.lastname: Popovic
authors.forename: Michael
authors.initials: M
authors.lastname: Förster
authors.forename: Malin
authors.initials: M
authors.lastname: Hultqvist
authors.forename: Dorota
authors.initials: D
authors.lastname: Klaczkowska
authors.forename: Ivanka
authors.initials: I
authors.lastname: Teneva
authors.forename: Martina
authors.initials: M
authors.lastname: Johannesson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
authors.forename: William
authors.initials: W
authors.lastname: Valdar
authors.forename: Kutty Selva
authors.initials: KS
authors.lastname: Nandakumar
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006239:Haplotypes; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D051379:Mice; D040641:Quantitative Trait Loci / Q000235:genetics