RGD Reference Report - Fine mapping reveals multiple loci and a possible epistatic interaction within the mammary carcinoma susceptibility quantitative trait locus, Mcs5. - Rat Genome Database

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Fine mapping reveals multiple loci and a possible epistatic interaction within the mammary carcinoma susceptibility quantitative trait locus, Mcs5.

Authors: Samuelson, DJ  Aperavich, BA  Haag, JD  Gould, MN 
Citation: Samuelson DJ, etal., Cancer Res. 2005 Nov 1;65(21):9637-42.
RGD ID: 1559294
Pubmed: (View Article at PubMed) PMID:16266982
DOI: Full-text: DOI:10.1158/0008-5472.CAN-05-1498

To identify high-frequency, low-penetrance breast cancer modifier genes, we have developed a rat genetic model that uses the Wistar-Kyoto (WKy) inbred strain, resistant to developing 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis, as a congenic donor and the susceptible Wistar-Furth (WF) strain as the recipient. Here, data from congenic rat lines containing smaller WKy genomic intervals of the Mcs5 quantitative trait locus region are presented to fine map three independently acting Mcs5 subloci. WKy-homozygous females from congenic lines defining Mcs5a, Mcs5b, and Mcs5c averaged, respectively, 4.0 +/- 0.4, 11.6 +/- 0.6, and 3.5 +/- 0.4 mammary carcinomas per rat. These phenotypic values are statistically different from the WF-homozygous phenotype value of 8.0 +/- 0.4, which is the baseline phenotype used for these experiments. We identified a likely Mcs5a x Mcs5b epistatic interaction that results in masking the increased susceptibility effect of the Mcs5b WKy allele by the Mcs5a WKy allele. We also provide evidence for a Mcs5a x Mcs5c interaction that is synergistic to decrease mammary carcinoma susceptibility below the additive effects of WKy alleles at each locus independently. The Mcs5 subloci are currently localized to 1.0, 7.5, and 4.5 Mb of rat chromosome 5, and the orthologous regions are on human chromosome 9 and mouse chromosome 4. These loci will provide unbiased candidate gene loci for evaluation in human case-control association studies.

Annotation

Disease Annotations    

Objects Annotated

QTLs
Mcs12  (Mammary carcinoma susceptibility QTL 12)
Mcs13  (Mammary carcinoma susceptibility QTL 13)
Mcs14  (Mammary carcinoma susceptibility QTL 14)

Objects referenced in this article
Marker D5Uwm63 D5Uwm63 Rattus norvegicus
Marker D5Uwm62 D5Uwm62 Rattus norvegicus
Marker D5Uwm65 D5Uwm65 Rattus norvegicus
Marker D5Uwm61 D5Uwm61 Rattus norvegicus
Marker D5Uwm68 D5Uwm68 Rattus norvegicus
Marker D5Uwm66 D5Uwm66 Rattus norvegicus
Marker D5Uwm64 D5Uwm64 Rattus norvegicus
Marker D5Uwm67 D5Uwm67 Rattus norvegicus
Marker D5Uwm60 D5Uwm60 Rattus norvegicus
Strain WF.WKY-(D5Uwm61-D5Uwm37)/Uwm null Rattus norvegicus
Strain WF.WKY-(D5Uwm63-D5Uwm60)/Uwm null Rattus norvegicus
Strain WF.WKY-(D5Uwm63-D5Uwm64)/Uwm null Rattus norvegicus
Strain WF.WKY-(D5Uwm65-D5Uwm60)/Uwm null Rattus norvegicus
Strain WF.WKY-(D5Uwm66-D5Uwm67)/Uwm null Rattus norvegicus
Strain WF.WKY-(D5Uwm68-D5Mit4)/Uwm null Rattus norvegicus
Strain WF.WKY-(D5Wox8-D5Uwm62)/Uwm null Rattus norvegicus

Additional Information