Genetic mapping of mammary tumor traits to rat chromosome 10 using a novel panel of consomic rats
Genetic mapping of mammary tumor traits to rat chromosome 10 using a novel panel of consomic rats
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DOI：
10.1016/j.cancergencyto.2008.05.014
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发表时间：
2008-10-01
影响因子：
--
通讯作者：
Sugg, Sonia L.
中科院分区：
文献类型：
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作者：
Adamovic, Tatjana;McAllister, Donna;Sugg, Sonia L.
在遗传多样性人群中鉴定新的乳腺癌易感性和耐药基因具有挑战性，因此使用传统的作图方法利用自交系大鼠来鉴定新的乳腺癌易感性定量性状位点（qtl）。QTL定位的另一种方法是使用染色体替代（consomic）大鼠菌株，该方法具有从consomic动物快速生成con基因的优点。使用一种新的大鼠菌株对，SS和BN，我们鉴定了两种经济大鼠菌株中的一种的大鼠乳腺癌qtl。用7,12-二甲基苯[a]蒽口服7,12-二甲基苯[a]蒽治疗近交系母鼠（SS和BN）和两种经济系母鼠（SS-10（BN）和SS-12(BN)）。评估肿瘤发生率、潜伏期和多样性的表型。SS大鼠对乳腺腺癌的发展高度敏感，而BN大鼠则完全耐药。对易感亲本和两个经济菌株的表型进行统计比较，鉴定出位于控制乳腺肿瘤潜伏期和多样性的第10染色体上的qtl。研究表明，SS-BN经济大鼠菌株可用于乳腺肿瘤qtl的定位。这种新方法将加速大鼠乳腺癌易感基因和耐药基因的定位克隆以及人类同源基因的鉴定。(C) 2008爱思唯尔公司版权所有。
Identification of novel breast cancer susceptibility and resistance genes in genetically diverse human populations is challenging, and so inbred rats have been used to identify novel mammary cancer susceptibility quantitative trait loci (QTLs) with conventional mapping approaches. An alternative approach for QTL mapping is to use chromosome substitution (consomic) rat strains, which has the advantage of rapid generation of congenic from consomic animals. Using a novel rat strain pair, SS and BN, we identified rat mammary cancer QTLs in one of two consomic rat strains tested. Female rats of inbred parental (SS and BN) and two consomic (SS-10(BN) and SS-12(BN)) strains were treated with 7,12-dimethylbenz[a]anthracene orally. The phenotypes of tumor incidence, latency, and multiplicity were evaluated. SS rats were highly susceptible to mammary adenocarcinoma development, whereas BN rats were completely resistant. Statistical comparison of the phenotypes between the susceptible parental and the two consomic strains identified QTLs residing within chromosome 10 controlling mammary tumor latency and multiplicity. The study shows that SS-BN consomic rat strains can be used to map mammary tumor QTLs. This novel approach should accelerate positional cloning of mammary cancer susceptibility and resistant genes in the rat and the identification of homologous genes in humans. (C) 2008 Elsevier Inc. All rights reserved.