Nucleotide variation in the p53 tumor-suppressor gene of voles from Chernobyl, Ukraine

Nucleotide variation in the p53 tumor-suppressor gene of voles from Chernobyl, Ukraine
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DOI:
10.1016/s1383-5718(98)00171-5
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发表时间:
1999-02-02
影响因子:
1.9
通讯作者:
DeWoody, JA
DeWoody, JA
中科院分区:
医学3区
文献类型:
--
作者:
DeWoody, JA

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1986年的切尔诺贝利核电站事故使乌克兰和白俄罗斯的大片地区受到各种放射性同位素和重金属的污染。虽然超过90%的放射性同位素已经衰变成稳定的化合物,但污染地区的辐射水平仍然非常高。事实上,一些生活在反应堆附近的啮齿动物体内的Cs-134,Cs-137浓度接近80 000 Bq/g。最近对脊椎动物进行的几项遗传分析表明,受切尔诺贝利辐射影响的生物体的突变率高于对照组,但没有人研究DNA序列。啮齿动物线粒体基因的核苷酸序列最初被报道为高变,但这些结果随后被撤回。在这里,我报告的结果,一个试点研究,以确定在p53基因的核苷酸变异的程度在四种啮齿动物(田鼠)从切尔诺贝利和控制网站。我测序了一个788 bp的区域(编码和非编码)的p53在30个不同的小鼠,包括四个不同物种的田鼠。在群体水平上的核苷酸变异是由于缺失和取代;两者都限于内含子。放射性人群和对照人群的单倍型数量之间无显著差异(p = 0.60)。罕见或私人等位基因可能是由于切尔诺贝利独特的突变压力而出现的。或者,自然选择可能偏爱一个等位基因而不是其他等位基因(即,选择性扫描)。这两种情况都没有得到这些数据的有力支持。因此,切尔诺贝利灾难对当地田鼠的p53基因没有明显的遗传影响;需要进行更广泛的调查,以确定切尔诺贝利灾难小鼠的突变率是否确实升高。然而,出现了两个突出的点,第一个涉及的实用程序的内含子作为标记的突变的编码区和第二个考虑的相对优点的克隆突变检测研究。(C)1999 Elsevier Science B. V.保留所有权利。
The 1986 Chernobyl disaster contaminated vast regions of Ukraine and Belarus with a variety of radioactive isotopes and heavy metals. While over 90% of the radioactive isotopes have decayed into stable compounds, radiation levels in contaminated areas are still extraordinarily high. In fact, some rodents living near the reactor have internal Cs-134,Cs-137 concentrations approaching 80 000 Bq/g. Several recent genetic analyses of vertebrates have illustrated that mutation rates of organisms exposed to radiation from Chernobyl are higher than in control groups, but none have studied DNA sequences. Nucleotide sequences of rodent mitochondrial genes were originally reported to have been hypervariable, but those results were subsequently retracted. Herein, I report the results of a pilot study to determine the extent of nucleotide variation at the p53 gene in four species of rodents (voles) from Chernobyl and from control sites. I sequenced a 788 bp region (coding and non-coding) of p53 in 30 different mice comprising four different species of Microtus. Nucleotide variation at the population level was due to deletions and substitutions; both were limited to introns. There were no significant differences between the number of haplotypes in radioactive and control populations (p = 0.60). Rare or private alleles might have arisen due to unique mutational pressures at Chernobyl. Alternatively; natural selection might have favored one allele over others (i.e., a selective sweep). Neither scenario is strongly supported by these data. Thus, no apparent genetic effects of the Chernobyl disaster on the p53 gene of resident voles were revealed; more extensive surveys will be necessary to determine if mutation rates are indeed elevated in mice from Chernobyl. However, two salient points emerge; the first involves the utility of introns as markers for mutations in coding regions and the second considers the relative merits of cloning in mutation detection studies. (C) 1999 Elsevier Science B.V. All rights reserved.