RGD Reference Report - Physical evidence of Mcs5, a QTL controlling mammary carcinoma susceptibility, in congenic rats. - Rat Genome Database

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Physical evidence of Mcs5, a QTL controlling mammary carcinoma susceptibility, in congenic rats.

Authors: Samuelson, DJ  Haag, JD  Lan, H  Monson, DM  Shultz, MA  Kolman, BD  Gould, MN 
Citation: Samuelson DJ, etal., Carcinogenesis 2003 Sep;24(9):1455-60. Epub 2003 Jul 04.
RGD ID: 631852
Pubmed: PMID:12844486   (View Abstract at PubMed)
DOI: DOI:10.1093/carcin/bgg112   (Journal Full-text)

Genetic susceptibility to breast cancer is influenced by high- and low-penetrance genes. The low-penetrance genes contributing to increased and decreased risk likely exist at appreciable frequencies in the human population. To identify high-frequency, low-penetrance modifier genes, we are using a rat genetic model. Eight quantitative trait loci, named mammary carcinoma susceptibility (Mcs) loci, have been genetically identified in two rat strains, Wistar-Kyoto (WKy) and Copenhagen. These strains are resistant to developing mammary cancer compared to susceptible Wistar-Furth (WF) female rats. Here we provide physical evidence of the existence of Mcs5 in the resistant WKy rat and further narrow the candidate region defining the QTL. Two congenic rat lines (C and D) containing large segments of the WKy Mcs5 QTL on chromosome 5 were generated on a WF background. The minimal WKy interval from markers D5Wox7 and D5Uwm37 (line C) conferred resistance to developing 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinomas. Line C females that were homozygous for the WKy allele at this interval averaged 1.1+/-0.3 carcinomas/rat compared to 6.9+/-0.4 average carcinomas/rat for WF control females (p<0.01). Line D females containing the minimal WKy interval from D5Rat26 to D5Uwm42, were as susceptible to developing mammary carcinomas as WF controls (5.7+/-0.6 vs. 6.9+/-0.4, respectively). The WKy region in common to these lines from D5Rat26 to D5Uwm37 is thus not expected to contain Mcs5-associated genes. Based on results presented here, the Mcs5 locus has been physically located within a congenic interval on rat chromosome 5 between markers D5Uwm8 and D5Rat26.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mamtr1RatExperimental Mammary Neoplasms  IAGP  RGD 
WF.WKY-(D5Rat26-D5Uwm42)/UwmRatExperimental Mammary Neoplasms inducedIAGP7,12-dimethyltetraphene (DMBA) RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
WF.WKY-(D5Pas1-D5Uwm37)/UwmRatdecreased incidence of tumors by chemical induction inducedIAGP7,12-dimethyltetraphene (DMBA)compared to WF/NHsdRGD 
Mamtr1Ratdecreased mammary gland tumor incidence  IAGP  RGD 
WF.WKY-(D5Pas1-D5Uwm37)/UwmRatdecreased mammary gland tumor incidence inducedIAGP7,12-dimethyltetraphene (DMBA)compared to WF/NHsdRGD 
WF/NHsdRatincreased incidence of tumors by chemical induction inducedIAGP7,12-dimethyltetraphene (DMBA)compared to WF.WKY-D5Wox7-D5Uwm37/UwmRGD 
WF/NHsdRatincreased mammary gland tumor incidence inducedIAGP7,12-dimethyltetraphene (DMBA)compared to WF.WKY-D5Wox7-D5Uwm37/UwmRGD 

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QTLs
Mamtr1  (Mammary tumor resistance QTL 1)


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