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.

译文

:在遗传多样的人群中鉴定新型乳腺癌易感性和耐药基因具有挑战性,因此近交大鼠已被用于通过常规作图方法鉴定新型乳腺癌易感性定量特征基因座(QTL)。 QTL作图的另一种方法是使用染色体替代(共生)大鼠品系,其优势在于可以从自体动物中快速产生同基因。使用一对新的大鼠品系SS和BN,我们在测试的两个纯合大鼠品系之一中鉴定了大鼠乳腺癌QTL。用7,12-二甲基苯并[a]蒽对雌性近交亲本(SS和BN)和两种交代(SS-10 BN和SS-12 BN)品系的雌性大鼠进行口服治疗。评价肿瘤发生率,潜伏期和多重性的表型。 SS大鼠对乳腺腺癌的发展高度敏感,而BN大鼠则完全耐药。易感的亲本和两个清毒株之间的表型的统计比较确定了驻留在染色体10中的QTL,这些QTL控制着乳腺肿瘤的潜伏期和多重性。研究表明,SS-BN清醒大鼠品系可用于绘制乳腺肿瘤QTL。这种新颖的方法应加快大鼠中乳腺癌的易感性和抗性基因的位置克隆,并加快人类同源基因的鉴定。

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