Bingham Jonathan L, Carrigan Patricia E, Miller Laurence J, Srinivasan Subha
Jivan Biologics, Inc., Larkspur, California 94939, USA.
OMICS. 2008 Mar;12(1):83-92. doi: 10.1089/omi.2007.0041.
Alternative splicing generates functional diversity in higher organisms through alternative first and last exons, skipped and included exons, intron retentions and alternative donor, and acceptor sites. In large-scale microarray studies in humans and the mouse, emphasis so far has been placed on exon-skip events, leaving the prevalence and importance of other splice types largely unexplored. Using a new human splice variant database and a genome-wide microarray to probes thousands of splice events of each type, we measured differential expression of splice types across six pair of diverse cell lines and validated the database annotation process. Results suggest that splicing in humans is more complex than simple exon-skip events, which account for a minority of splicing differences. The relative frequency of differential expression of the splice types correlates with what is found by our annotation efforts. In conclusion, alternative splicing in human cells is considerably more complex than the canonical example of the exon skip. The complementary approaches of genome-wide annotation of alternative splicing in human and design of genome-wide splicing microarrays to measure differential splicing in biological samples provide a powerful high-throughput tool to study the role of alternative splicing in human biology.
可变剪接通过可变的首个和末个外显子、跳跃和包含的外显子、内含子保留以及可变供体和受体位点，在高等生物中产生功能多样性。在人类和小鼠的大规模微阵列研究中，迄今为止重点一直放在外显子跳跃事件上，其他剪接类型的普遍性和重要性在很大程度上尚未得到探索。利用一个新的人类剪接变体数据库和全基因组微阵列来探测每种类型的数千个剪接事件，我们测量了六种不同细胞系对中各剪接类型的差异表达，并验证了数据库注释过程。结果表明，人类中的剪接比简单的外显子跳跃事件更为复杂，外显子跳跃事件仅占剪接差异的少数。剪接类型差异表达的相对频率与我们注释工作的结果相关。总之，人类细胞中的可变剪接比外显子跳跃的典型例子要复杂得多。对人类可变剪接进行全基因组注释以及设计全基因组剪接微阵列以测量生物样品中的差异剪接这两种互补方法，提供了一个强大的高通量工具来研究可变剪接在人类生物学中的作用。
