Exclusion of the 750-kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy in HPCX1-linked families.
Exclusion of the 750-kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy in HPCX1-linked families.
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DOI：
10.1002/gcc.21977
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发表时间：
2012-10
影响因子：
3.7
通讯作者：
Larionov, Vladimir
中科院分区：
文献类型：
--
作者：
Kouprina, Natalay;Lee, Nicholas C. O.;Pavlicek, Adam;Samoshkin, Alexander;Kim, Jung-Hyun;Lee, Hee-Sheung;Varma, Sudhir;Reinhold, William C.;Otstot, John;Solomon, Greg;Davis, Sean;Meltzer, Paul S.;Schleutker, Johanna;Larionov, Vladimir
几项连锁研究提供了 Xq27-q28 处遗传性前列腺癌基因座 HPCX1 存在的证据。前列腺癌的最强连锁峰覆盖了 Xq27 处约 750 kb 的可变区，该可变区富含节段重复 (SD)，表明前列腺癌的易感性可能是由 SD 之间的重组相互作用引起的基因组疾病。 SD 的大尺寸及其序列相似性使得很难使用标准方法检查该区域是否可能发生重排。为了克服这个问题，通过酵母体内重组直接分离一组基因组片段（TAR 克隆技术），用于对 X 连锁家族的 750 kb 区域进行突变分析。我们没有检测到该区域内疾病特异性的重排。此外，还进行了转录组和计算分析，以寻找 Xq27 区域内未注释的基因，这些基因可能与前列腺癌的遗传易感性相关。确定了两个候选基因，其中一个是名为 SPANXL 的新基因，它代表 SPANX 基因家族中高度分化的成员，另一个是先前描述的 CDR1 基因，该基因在正常和恶性前列腺细胞中均高水平表达，定位于 SPANX 基因簇上游 210 kb。这些基因中没有发现疾病特异性的改变。总而言之，我们的结果排除了 Xq27 的 750 kb 遗传不稳定区域作为前列腺恶性肿瘤的候选位点。邻近区域似乎是最有可能识别难以捉摸的 HPCX1 基因座的候选区域。
Several linkage studies provided evidence for the presence of the hereditary prostate cancer locus, HPCX1, at Xq27-q28. The strongest linkage peak of prostate cancer overlies a variable region of ~750 kb at Xq27 enriched by segmental duplications (SDs), suggesting that the predisposition to prostate cancer may be a genomic disorder caused by recombinational interaction between SDs. The large size of SDs and their sequence similarity make it difficult to examine this region for possible rearrangements using standard methods. To overcome this problem, direct isolation of a set of genomic segments by in vivo recombination in yeast (a TAR cloning technique) was used to perform a mutational analysis of the 750 kb region in X-linked families. We did not detect disease-specific rearrangements within this region. In addition, transcriptome and computational analyses were performed to search for non-annotated genes within the Xq27 region, which may be associated with genetic predisposition to prostate cancer. Two candidate genes were identified, one of which is a novel gene termed SPANXL that represents a highly diverged member of the SPANX gene family, and the previously described CDR1 gene that is expressed at a high level in both normal and malignant prostate cells, and mapped 210 kb of upstream the SPANX gene cluster. No disease-specific alterations were identified in these genes. To summarize, our results exclude the 750-kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy. Adjacent regions appear to be the most likely candidates to identify the elusive HPCX1 locus.
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DOI：
10.1093/bioinformatics/btq224
发表时间：
2010-08-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Katoh K;Toh H
通讯作者：
Toh H
影响因子：
14.8
作者：
Kouprina, Natalay;Larionov, Vladimir
通讯作者：
Larionov, Vladimir
影响因子：
5.3
作者：
Baffoe-Bonnie, AB;Smith, JB;Bailey-Wilson, JE
通讯作者：
Bailey-Wilson, JE
影响因子：
56.9
作者：
Bailey, JA;Gu, ZP;Eichler, EE
通讯作者：
Eichler, EE
影响因子：
2.8
作者：
Bochum, S;Paiss, T;Haeussler, J
通讯作者：
Haeussler, J