title: Physical Confirmation and Comparative Genomics of the RatMammary carcinoma susceptibility 3Quantitative Trait Locus.
abstract: Human breast and rat mammary cancer susceptibility are complex phenotypes where complete sets of risk associated loci remain to be identified for both species. We tested multiple congenic rat strains to physically confirm and positionally map ratMammary carcinoma susceptibility 3(Mcs3)-a mammary cancer resistance allele previously predicted atRattus norvegicuschromosome 1 (RNO1). The mammary cancer susceptible Wistar Furth (WF) strain was the recipient, and the mammary cancer resistant Copenhagen (Cop) strain was theRNO1-segment donor for congenics. Inbred WF females averaged 6.3 carcinogen-induced mammary carcinomas per rat. Two WF.Cop congenic strains averaged 2.8 and 3.4 mammary carcinomas per rat, which confirmedMcs3as an independently acting allele. Two other WF.Cop congenic strains averaged 6.6 and 8.1 mammary carcinomas per rat, and, thus, did not containMcs3RatMcs3was delimited to 27.8 Mb ofRNO1fromrs8149408tors105131702(RNO1:143700228-171517317 of RGSC 6.0/rn6). Human genetic variants withpvalues for association to breast cancer risk below 10-7had not been reported forMcs3orthologous loci; however, human variants located inMcs3-orthologous regions with potential association to risk (10-7<p< 10-3) were listed in some population-based studies. Further, ratMcs3contains sequence orthologous to human11q13/14-a region frequently amplified in female breast cancer. We conclude thatMcs3is an independently acting mammary carcinoma resistance allele. Human population-based, genome-targeted association studies interrogatingMcs3orthologous loci may yield novel breast cancer risk associated variants and genes.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Kentucky 40292.
authors.forename: Saasha
authors.initials: S
authors.lastname: Le
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Kentucky 40292.
authors.forename: Zachary C
authors.initials: ZC
authors.lastname: Martin
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Kentucky 40292 david.samuelson@louisville.edu.|James Graham Brown Cancer Center, University of Louisville School of Medicine, Kentucky 40202.|Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Kentucky 40202.
authors.forename: David J
authors.identifier: 0000-0003-4171-1362
authors.initials: DJ
authors.lastname: Samuelson
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D001947:Breeding; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats
keywords: breast cancer susceptibility; mammary carcinogenesis; rat QTL