title: Linkage disequilibrium and haplotype mapping of a skin cancer susceptibility locus in outbred mice.
abstract: Car-R (carcinogenesis-resistant) and Car-S (carcinogenesis-susceptible) outbred mice, obtained by phenotypic selection from an initial intercross of eight inbred strains, show a >100-fold difference in their susceptibility to two-stage skin tumorigenesis. We found that the lines carry a high degree of genetic polymorphism. with an average heterozygosity of 0.39. This polymorphism allowed the use of linkage disequilibrium (LD) and haplotype analysis for the mapping of a skin cancer modifier locus on Chr 7, in a short region of 6 cM, around the Tyr gene. Car-S mice inherited the susceptibility allele at this locus from the A/J, BALB/c, SJL/J, and SWR/J strains. Our results demonstrate the feasibility and usefulness of mapping disease genes by LD in phenotypically selected, genetically heterogeneous animals.
authors.affiliation: Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Peissel
authors.forename: D
authors.initials: D
authors.lastname: Zaffaroni
authors.forename: N
authors.initials: N
authors.lastname: Zanesi
authors.forename: I
authors.initials: I
authors.lastname: Zedda
authors.forename: G
authors.initials: G
authors.lastname: Manenti
authors.forename: S
authors.initials: S
authors.lastname: Rebessi
authors.forename: S
authors.initials: S
authors.lastname: Pazzaglia
authors.forename: G
authors.initials: G
authors.lastname: Doria
authors.forename: V
authors.initials: V
authors.lastname: Covelli
authors.forename: T A
authors.initials: TA
authors.lastname: Dragani
authors.forename: A
authors.initials: A
authors.lastname: Saran
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains / Q000235:genetics*; D002875:Chromosomes; D003433:Crosses, Genetic; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006579:Heterozygote; D015810:Linkage Disequilibrium; D051379:Mice; D008815:Mice, Inbred Strains; D018895:Microsatellite Repeats; D009374:Neoplasms, Experimental / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*