The human telomerase gene:: complete genomic sequence and analysis of tandem repeat polymorphisms in intronic regions
The human telomerase gene:: complete genomic sequence and analysis of tandem repeat polymorphisms in intronic regions
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DOI：
10.1038/sj.onc.1205122
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发表时间：
2002-01-24
期刊：
影响因子：
8
通讯作者：
Larionov, V
中科院分区：
文献类型：
--
作者：
Leem, SH;Londoño-Vallejo, JA;Larionov, V
在这项工作中，全长hTERT基因的分离和以前未知的区域在内含子6以及上游和下游hTERT区域的序列进行了测定。我们已经表明，内含子6包括一个可变数目的串联重复序列（VNTR）的38 bp的序列，（hTERT-VNTR 6-1）。在103个无关个体中检测到8个hTERT-VNTR 6-1等位基因，重复数在27 ~ 47之间。hTERT-VNTR 2-2是在hTERT内含子2中发现的另一个新的61 bp小卫星重复序列。hTERT-VNTR 2-2的至少四个等位基因可被区分。先前的研究已经描述了小卫星hTERT-VNTR 2-1（内含子2中的42 bp重复）和hTERT-VNTR 6-2（内含子6中的36 bp重复）的多态性。这些，再加上在内含子12中发现的另一个小卫星，在hTERT基因中增加了五个这样的结构。hTERT小卫星的分离在家庭中进行了分析，揭示了VNTR通过孟德尔遗传后的减数分裂传递。hTERT中的小卫星也在来自肿瘤患者的匹配的正常和癌组织中进行了分析;在一名肾肿瘤患者中，内含子6中的两个VNTR经历了伴随的重排。这一观察结果表明，染色体重排牵连这些VNTRs可能与端粒酶表达的癌细胞中的激活。
In this work, the full-length hTERT gene was isolated and the sequence of the previously unknown region in intron 6 as well as that of upstream and downstream hTERT regions was determined. We have shown that intron 6 includes a variable number of tandem repeats (VNTR) of a 38 bp sequence, (hTERT-VNTR 6-1). Eight alleles of hTERT-VNTR 6-1 were identified among 103 unrelated individuals, ranging front 27 to 47 repeats. hTERT-VNTR 2-2 is another new 61 bp minisatellite repeat found in intron 2 of hTERT. At least four alleles of hTERT-VNTR 2-2 can be distinguished. Previous studies have described polymorphisms for minisatellites hTERT-VNTR 2-1, a 42 bp repeat in intron 2, and hTERT-VNTR 6-2, a 36 bp repeat in intron 6. These, together with another minisatellite found in intron 12, add up to five such structures within the hTERT gene. The segregation of hTERT minisatellites was analysed in families, revealing that the VNTRs are transmitted through meiosis following a Mendelian inheritance. Minisatellites in hTERT were also analysed in matching normal and cancer tissues from patients with tumors; in one patient with a kidney tumor, the two VNTRs in intron 6 had undergone concomitant rearrangements. This observation suggests that chromosomal rearrangements implicating these VNTRs may be associated with the activation of telomerase expression in cancer cells.