RGD Reference Report - Physical Confirmation and Mapping of Overlapping Rat Mammary Carcinoma Susceptibility QTLs, Mcs2 and Mcs6. - Rat Genome Database

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Physical Confirmation and Mapping of Overlapping Rat Mammary Carcinoma Susceptibility QTLs, Mcs2 and Mcs6.

Authors: Sanders, J  Haag, JD  Samuelson, DJ 
Citation: Sanders J, etal., PLoS One. 2011;6(5):e19891. Epub 2011 May 18.
RGD ID: 5133689
Pubmed: PMID:21625632   (View Abstract at PubMed)
PMCID: PMC3097214   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0019891   (Journal Full-text)

Only a portion of the estimated heritability of breast cancer susceptibility has been explained by individual loci. Comparative genetic approaches that first use an experimental organism to map susceptibility QTLs are unbiased methods to identify human orthologs to target in human population-based genetic association studies. Here, overlapping rat mammary carcinoma susceptibility (Mcs) predicted QTLs, Mcs6 and Mcs2, were physically confirmed and mapped to identify the human orthologous region. To physically confirm Mcs6 and Mcs2, congenic lines were established using the Wistar-Furth (WF) rat strain, which is susceptible to developing mammary carcinomas, as the recipient (genetic background) and either Wistar-Kyoto (WKy, Mcs6) or Copenhagen (COP, Mcs2), which are resistant, as donor strains. By comparing Mcs phenotypes of WF.WKy congenic lines with distinct segments of WKy chromosome 7 we physically confirmed and mapped Mcs6 to approximately 33 Mb between markers D7Rat171 and gUwm64-3. The predicted Mcs2 QTL was also physically confirmed using segments of COP chromosome 7 introgressed into a susceptible WF background. The Mcs6 and Mcs2 overlapping genomic regions contain multiple annotated genes, but none have a clear or well established link to breast cancer susceptibility. Igf1 and Socs2 are two of multiple potential candidate genes in Mcs6. The human genomic region orthologous to rat Mcs6 is on chromosome 12 from base positions 71,270,266 to 105,502,699. This region has not shown a genome-wide significant association to breast cancer risk in pun studies of breast cancer susceptibility.




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Objects referenced in this article
Marker D7Uwm23 D7Uwm23 Rattus norvegicus
Marker D7Uwm24 D7Uwm24 Rattus norvegicus
Marker D7Uwm25 D7Uwm25 Rattus norvegicus
Marker D7Uwm26 D7Uwm26 Rattus norvegicus
QTL Mcs2 Mammary carcinoma susceptibility QTL 2 Rattus norvegicus
QTL Mcs6 Mammary carcinoma susceptibility QTL 6 Rattus norvegicus

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