Linkage disequilibrium and haplotype mapping of a skin cancer susceptibility locus in outbred mice.
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.
Peissel
B
B
Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
Zaffaroni
D
D
Zanesi
N
N
Zedda
I
I
Manenti
G
G
Rebessi
S
S
Pazzaglia
S
S
Doria
G
G
Covelli
V
V
Dragani
T A
TA
Saran
A
A
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*