Linkage disequilibrium and haplotype mapping of a skin cancer susceptibility locus in outbred mice |
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| Authors: | Bernard Peissel Daniela Zaffaroni Nicola Zanesi Ignazio Zedda Giacomo Manenti Simonetta Rebessi Simonetta Pazzaglia Gino Doria Vincenzo Covelli Tommaso A Dragani Anna Saran |
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| Institution: | (1) Department of Experimental Oncology, Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milan, Italy, IT;(2) ENEA, Rome, Italy, IT;(3) Department of Molecular Biology, University of Rome, Tor Vergata, Rome, Italy, IT |
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| 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.
Received: 16 March 2000 / Accepted: 9 June 2000 |
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