Physical evidence of Mcs5, a QTL controlling mammary carcinoma susceptibility, in congenic rats.
Physical evidence of Mcs5, a QTL controlling mammary carcinoma susceptibility, in congenic rats.
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Mcs5（一种控制乳腺癌易感性的 QTL）在同系大鼠中的物理证据。
DOI：
10.1093/carcin/bgg112
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Gould,MichaelN
中科院分区：
文献类型：
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作者：
Samuelson,DavidJ;Haag,JillD;Lan,Hong;Monson,DinelliM;Shultz,MillicentA;Kolman,BradleyD;Gould,MichaelN
乳腺癌的遗传易感性受高外显性和低外显性基因的影响。导致风险增加和降低的低外显性基因可能以相当高的频率存在于人类群体中。为了识别高频、低外显率的修饰基因，我们使用了一个大鼠遗传模型。在Wistar-京都(WKY)和哥本哈根两个品系的大鼠中，已经发现了8个数量性状基因座，称为乳腺癌易感性(MCS)基因座。与敏感的Wistar-Furth(WF)雌性大鼠相比，这些品系对发生乳腺癌具有抵抗力。在这里，我们提供了在抗性WKY大鼠中存在Mcs5的物理证据，并进一步缩小了定义QTL的候选区域。在WF背景下产生了两个含有5号染色体上WKyMcs5QTL大片段的同源大鼠品系(C和D)。标记D5Wox7和D5Uwm37(C系)的最小WKY间隔对7，12-二甲基苯并[a]菲(DMBA)诱发的乳腺癌具有抗性。在这一区间内，WKY等位基因纯合的C系雌性大鼠平均患癌数为1.1±0.3个/只，而对照组为6.9±0.4个(P<；0.01)。WKY间期在D5Rat26至D5Uwm42之间的D系女性患乳腺癌的易感性与WF对照组相同(分别为5.7±0.6和6.9±0.4)。因此，从D5Rat26到D5Uwm37的这些品系所共有的WKY区域预计不包含Mcs5相关基因。根据本文提出的结果，Mcs5基因座在物理上位于大鼠5号染色体上标记D5Uwm8和D5Rat26之间的同源区间内。
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 with susceptible Wistar-Furth (WF) female rats. Here we provide physical evidence of the existence ofMcs5in 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 WKyMcs5QTL on chromosome5were generated on a WF background. The minimal WKy interval from markersD5Wox7andD5Uwm37(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 with 6.9±0.4 average carcinomas/rat for WF control females (P<0.01). Line D females containing the minimal WKy interval fromD5Rat26toD5Uwm42, were as susceptible to developing mammary carcinomas as WF controls (5.7±0.6 versus 6.9±0.4, respectively). The WKy region in common to these lines fromD5Rat26toD5Uwm37is thus not expected to containMcs5-associated genes. Based on results presented here, theMcs5locus has been physically located within a congenic interval on rat chromosome5between markersD5Uwm8andD5Rat26.