Global screening and extended nomenclature for 230 aphidicolin-inducible fragile sites, including 61 yet unreported ones
Global screening and extended nomenclature for 230 aphidicolin-inducible fragile sites, including 61 yet unreported ones
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DOI：
10.3892/ijo_00000572
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发表时间：
2010-04-01
影响因子：
5.2
通讯作者：
Weise, Anja
中科院分区：
文献类型：
--
作者：
Mrasek, Kristin;Schoder, Christiane;Weise, Anja
自从人类脆性位点（fragile sites，FS）首次被发现以来，已有40多年的研究报道了多种物质在染色体非随机、易断裂区域诱导断裂。根据人类基因组浏览器aphidicolin提供的信息，DNA复制抑制剂诱导88种已知常见FS中的77种。然而，在文献中报道了另外的FS，其也至少部分地由蚜霉素诱导。据我们所知，在这里，我们提出了第一个也是最大的有史以来做系统的，全基因组定向和全面的筛选aphidicolin诱导的断裂倾向的地区。该研究是在3个无关健康个体的刺激的外周血淋巴细胞上进行的。分析了25000个中期扩散，记录了位于230个不同基因座的总共22,537个FS。其中61个FS以前从未被观察到，52个以前已经报道过，但没有被包括在基因组浏览器中，尚未得到验证。有趣的是，aphidicolin能够诱导所有类型的罕见和常见的FS，这表明这些容易断裂的区域比最初假设的更少依赖于诱导化学物质。总的来说，我们提供了第一个全面的全基因组图谱FS和研究可能的相关性染色体长度和GTG显带水平与FS频率。为了更好地处理FS在未来，已经存在的字母命名法FS单染色体上的扩展建议。
Since the first description of human fragile sites (FS) inore than 40 years ago, a variety substances were reported to induce chromosomal breaks at non-random, breakage-prone regions. According to information available from human genome browsers aphidicolin, an inhibitor of DNA replication induces 77 of 88 known common FS. However, in the literature additional FS are reported, which are also, at least in part, inducible by aphidicolin. To the best of our knowledge, here we present the first and largest ever done systematic, whole genome-directed and comprehensive screening for aphidicolin-inducible breakage-prone regions. The study was performed on stimulated peripheral blood lymphocytes of 3 unrelated healthy individuals. Twenty-five thousand metaphase spreads were analyzed and overall 22,537 FS located in 230 different loci were recorded. Sixty-one of those FS were never observed before and 52 were already previously reported but not included in genome browsers and yet verified. Interestingly, aphidicolin was able to induce all types of rare and common FS, suggesting that these breakage-prone regions are less dependent on the inducing chemicals than originally supposed. Overall, we provide the first comprehensive genome wide map for FS and studied possible correlations of chromosome length and GTG-banding level with FS-frequency. To handle FS better in future, an extension of the already existing alphabetical nomenclature for FS on single chromosomes is suggested.