Shao Xiang, Shepelev Valery, Fedorov Alexei
Department of Medicine and Program in Bioinformatics and Proteomics/Genomics, Medical University of Ohio, Toledo, 43614, USA.
Bioinformatics. 2006 Mar 15;22(6):692-8. doi: 10.1093/bioinformatics/bti795. Epub 2005 Nov 24.
Using bioinformatic approaches we aimed to characterize poorly understood abnormalities in splicing known as exon scrambling, exon repetition and trans-splicing.
We developed a software package that allows large-scale comparison of all human expressed sequence tags (EST) sequences to the entire set of human gene sequences. Among 5,992,495 EST sequences, 401 cases of exon repetition and 416 cases of exon scrambling were found. The vast majority of identified ESTs contain fragments rather than full-length repeated or scrambled exons. Their structures suggest that the scrambled or repeated exon fragments may have arisen in the process of cDNA cloning and not from splicing abnormalities. Nevertheless, we found 11 cases of full-length exon repetition showing that this phenomenon is real yet very rare. In searching for examples of trans-splicing, we looked only at reproducible events where at least two independent ESTs represent the same putative trans-splicing event. We found 15 ESTs representing five types of putative trans-splicing. However, all 15 cases were derived from human malignant tissues and could have resulted from genomic rearrangements. Our results provide support for a very rare but physiological occurrence of exon repetition, but suggest that apparent exon scrambling and trans-splicing result, respectively, from in vitro artifact and gene-level abnormalities.
Exon-Intron Database (EID) is available at http://www.meduohio.edu/bioinfo/eid. Programs are available at http://www.meduohio.edu/bioinfo/software.html. The Laboratory website is available at http://www.meduohio.edu/medicine/fedorov
Supplementary file is available at http://www.meduohio.edu/bioinfo/software.html.
我们旨在利用生物信息学方法来描述那些了解较少的剪接异常，即外显子重排、外显子重复和反式剪接。
我们开发了一个软件包，可对所有人类表达序列标签（EST）序列与整个人类基因序列集进行大规模比较。在5992495条EST序列中，发现了401例外显子重复和416例外显子重排。绝大多数已识别的EST包含片段而非全长重复或重排的外显子。它们的结构表明，重排或重复的外显子片段可能是在cDNA克隆过程中产生的，而非来自剪接异常。然而，我们发现了11例全长外显子重复，表明这种现象是真实存在的，但非常罕见。在寻找反式剪接的例子时，我们只关注可重复的事件，即至少有两个独立的EST代表相同的假定反式剪接事件。我们发现了15条代表五种假定反式剪接类型的EST。然而，所有15例均来自人类恶性组织，可能是基因组重排导致的。我们的结果支持了外显子重复是一种非常罕见但生理上会发生的现象，但表明明显的外显子重排和反式剪接分别是体外假象和基因水平异常导致的。
外显子-内含子数据库（EID）可在http://www.meduohio.edu/bioinfo/eid获取。程序可在http://www.meduohio.edu/bioinfo/software.html获取。实验室网站可在http://www.meduohio.edu/medicine/fedorov获取。
