Notl flanking sequences:: a tool for gene discovery and verification of the human genome
Notl flanking sequences:: a tool for gene discovery and verification of the human genome
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DOI：
10.1093/nar/gkf428
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发表时间：
2002-07-15
影响因子：
14.9
通讯作者：
Zabarovsky, ER
中科院分区：
文献类型：
--
作者：
Kutsenko, AS;Gizatullin, RZ;Zabarovsky, ER
生成了一组 22 551 个独特的人 NotI 侧翼序列 (16.2 Mb)。该组中超过 40% 的区域与已知蛋白质和表达序列具有显着相似性。数据表明NotI位点侧翼的区域不太可能有效地形成核小体并且类似于启动子区域。人类基因组序列草案包含 55.7% 的 Notl 侧翼序列，Celera 的数据库包含与 57.2% 克隆的匹配，所有公共数据库（包括非人类和先前测序的 Notl 侧翼）匹配 89.2% 的 Notl 侧翼序列（至少 50 bp 的同一性大于或等于 90%，数据来自 2001 年 12 月）。数据表明，用于生成人类基因组序列草案的鸟枪测序方法导致了对 Notl 侧翼克隆和测序的偏见。粗略估计（主要基于 21 号和 22 号染色体）人类基因组包含 15 000-20 000 个 Notl 位点，其中 6000-9000 个在任何特定细胞中未甲基化。研究结果表明，现有的计算确定 CpG 岛的工具无法识别很大一部分功能性 CpG 岛，即使在 CG 含量较低的区域也可以发现具有高频率 CpG 二核苷酸的非甲基化 DNA 片段。
A set of 22 551 unique human Notl flanking sequences (16.2 Mb) was generated. More than 40% of the set had regions with significant similarity to known proteins and expressed sequences. The data demonstrate that regions flanking Notl sites are less likely to form nucleosomes efficiently and resemble promoter regions. The draft human genome sequence contained 55.7% of the Notl flanking sequences, Celera's database contained matches to 57.2% of the clones and all public databases (including non-human and previously sequenced Notl flanks) matched 89.2% of the Notl flanking sequences (identity greater than or equal to90% over at least 50 bp, data from December 2001). The data suggest that the shotgun sequencing approach used to generate the draft human genome sequence resulted in a bias against cloning and sequencing of Notl flanks. A rough estimation (based primarily on chromosomes 21 and 22) is that the human genome contains 15 000-20 000 Notl sites, of which 6000-9000 are unmethylated in any particular cell. The results of the study suggest that the existing tools for computational determination of CpG islands fail to identify a significant fraction of functional CpG islands, and unmethylated DNA stretches with a high frequency of CpG dinucleotides can be found even in regions with low CG content.