Physical Confirmation and Mapping of Overlapping Rat Mammary Carcinoma Susceptibility QTLs, Mcs2 and Mcs6
Physical Confirmation and Mapping of Overlapping Rat Mammary Carcinoma Susceptibility QTLs, Mcs2 and Mcs6
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DOI：
10.1371/journal.pone.0019891
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发表时间：
2011-05-18
期刊：
影响因子：
3.7
通讯作者：
Samuelson, David J.
中科院分区：
文献类型：
--
作者：
Sanders, Jennifer;Haag, Jill D.;Samuelson, David J.
乳腺癌易感性的估计遗传力中只有一部分可以通过个体基因座来解释。首先使用实验生物体来绘制易感性 QTL 的比较遗传学方法是在基于人群的遗传关联研究中识别人类直系同源物的无偏见方法。在此，对重叠的大鼠乳腺癌易感性 (Mcs) 预测 QTL、Mcs6 和 Mcs2 进行了物理确认和绘图，以识别人类直系同源区域。为了在物理上确认 Mcs6 和 Mcs2，使用易患乳腺癌的 Wistar-Furth (WF) 大鼠品系作为受体（遗传背景），以及具有抗性的 Wistar-Kyoto (WKy、Mcs6) 或 Copenhagen (COP、Mcs2) 作为供体品系，建立了同源系。通过比较 WF 的 Mcs 表型。我们对具有 WKy 7 号染色体不同片段的 WKy 同系系进行了物理确认，并将 Mcs6 映射到标记 D7Rat171 和 gUwm64-3 之间类似于 33 Mb 的位置。预测的 Mcs2 QTL 还使用渗入易感 WF 背景的 COP 7 号染色体片段进行了物理证实。 Mcs6 和 Mcs2 重叠的基因组区域包含多个注释基因，但没有一个与乳腺癌易感性具有明确或明确的联系。 Igf1 和 Socs2 是 Mcs6 中多个潜在候选基因中的两个。与大鼠 Mcs6 直系同源的人类基因组区域位于 12 号染色体上，碱基位置 71,270,266 至 105,502,699。在乳腺癌易感性的双关语研究中，该区域并未显示出与乳腺癌风险在全基因组范围内的显着关联。
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 similar to 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.