Linkage disequilibrium and haplotype mapping of a skin cancer susceptibility locus in outbred mice

• DOI: 10.1007/s003350010184
• Publication Date: 2002-08-25T06:16:17Z
• Authors: Bernard Peissel; Daniela Zaffaroni; Nicola Zanesi; Ignazio Zedda; Giacomo Manenti; Simonetta Rebessi; Simonetta Pazzaglia; Gino Doria; Vincenzo Covelli; Tommaso A. Dragani; Anna Saran
• Keywords: Heterozygote; 0303 health sciences; Skin Neoplasms; Mice, Inbred Strains; Neoplasms, Experimental; Chromosomes; Linkage Disequilibrium; 3. Good health; Mice; 03 medical and health sciences; Haplotypes; Animals, Outbred Strains; Animals; Genetic Predisposition to Disease; Crosses, Genetic; Microsatellite Repeats

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.