Identification and analysis of alternative splicing events conserved in human and mouse

DOI Web Site 被引用文献7件
  • Gene W. Yeo
    Departments of Biology and Brain and Cognitive Sciences and Center for Biological and Computational Learning, Massachusetts Institute of Technology, Cambridge, MA 02319
  • Eric Van Nostrand
    Departments of Biology and Brain and Cognitive Sciences and Center for Biological and Computational Learning, Massachusetts Institute of Technology, Cambridge, MA 02319
  • Dirk Holste
    Departments of Biology and Brain and Cognitive Sciences and Center for Biological and Computational Learning, Massachusetts Institute of Technology, Cambridge, MA 02319
  • Tomaso Poggio
    Departments of Biology and Brain and Cognitive Sciences and Center for Biological and Computational Learning, Massachusetts Institute of Technology, Cambridge, MA 02319
  • Christopher B. Burge
    Departments of Biology and Brain and Cognitive Sciences and Center for Biological and Computational Learning, Massachusetts Institute of Technology, Cambridge, MA 02319

書誌事項

公開日
2005-02-11
DOI
  • 10.1073/pnas.0409742102
公開者
Proceedings of the National Academy of Sciences

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説明

<jats:p> Alternative pre-mRNA splicing affects a majority of human genes and plays important roles in development and disease. Alternative splicing (AS) events conserved since the divergence of human and mouse are likely of primary biological importance, but relatively few of such events are known. Here we describe sequence features that distinguish exons subject to evolutionarily conserved AS, which we call alternative conserved exons (ACEs), from other orthologous human/mouse exons and integrate these features into an exon classification algorithm, <jats:sc>acescan</jats:sc> . Genome-wide analysis of annotated orthologous human–mouse exon pairs identified ≈2,000 predicted ACEs. Alternative splicing was verified in both human and mouse tissues by using an RT-PCR-sequencing protocol for 21 of 30 (70%) predicted ACEs tested, supporting the validity of a majority of <jats:sc>acescan</jats:sc> predictions. By contrast, AS was observed in mouse tissues for only 2 of 15 (13%) tested exons that had EST or cDNA evidence of AS in human but were not predicted ACEs, and AS was never observed for 11 negative control exons in human or mouse tissues. Predicted ACEs were much more likely to preserve the reading frame and less likely to disrupt protein domains than other AS events and were enriched in genes expressed in the brain and in genes involved in transcriptional regulation, RNA processing, and development. Our results also imply that the vast majority of AS events represented in the human EST database are not conserved in mouse. </jats:p>

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