Analysis of genetic variations in the exon 27 region of the canine BRCA2 locus
Analysis of genetic variations in the exon 27 region of the canine BRCA2 locus
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DOI：
10.1292/jvms.67.1013
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发表时间：
2005-10-01
影响因子：
1.2
通讯作者：
Hashizume, K
中科院分区：
文献类型：
--
作者：
Yoshikawa, Y;Morimatsu, M;Hashizume, K
乳腺肿瘤是女性最常见的肿瘤类型，在雌性狗中也是如此。BRCA2基因编码一种参与DNA修复的大型核蛋白，人类BRCA2基因的突变会增加女性乳腺癌的风险。BRCA2蛋白作为一种肿瘤抑制因子，其杂合性缺失导致BRCA2失活与乳腺癌的发生有关。为了建立犬BRCA2基因杂合性缺失分析的多态标记，我们分析了30只有乳腺肿瘤的犬和21只无瘤犬的BRCA2基因外显子27的基因组序列。除了10204ins/delAAA之外，我们还发现了四个新的单核苷酸多态，这是之前唯一发现的犬BRCA2基因座的多态。对这5个等位基因的分析表明，存在4种等位基因类型。由于10204ins/delAAA是已鉴定的五个多态中最常见的，我们建立了一种基于PCR的分析方法来检测这种多态。我们认为，该方法对于分析犬BRCA2基因在肿瘤发病机制中的杂合性丢失具有重要价值。
Mammary tumors are the most common tumor type in women as well as in female dogs. The BRCA2 gene encodes a large nuclear protein that is involved in DNA repair, and mutations in the human BRCA2 confer an increased risk of female mammary tumors. The BRCA2 protein acts as a tumor suppressor, and inactivation of BRCA2 by loss of heterozygosity is implicated in mammary carcinogenesis. In this study, to establish an appropriate polymorphic marker for loss of heterozygosity analysis of the canine BRCA2, we analyzed the genomic sequences of the exon 27 regions of 30 mammary-tumor-bearing and 21 tumor-free dogs. In addition to 10204ins/delAAA, which is the only polymorphism previously identified for the canine BRCA2 locus, we discovered four novel single nucleotide polymorphisms. The analysis of these five polymorphisms revealed the presence of four allele types. Since 10204ins/delAAA was the most common of the five polymorphisms identified, we developed a PCR-based assay method to assay for this polymorphism. We believe that this method is valuable for loss of heterozygosity analysis of the canine BRCA2 gene in tumor pathogenesis.