Genome-wide detection of tissue-specific alternative splicing in the human transcriptome

Nucleic Acids Res. 2002 Sep 1;30(17):3754-66. doi: 10.1093/nar/gkf492.


We have developed an automated method for discovering tissue-specific regulation of alternative splicing through a genome-wide analysis of expressed sequence tags (ESTs). Using this approach, we have identified 667 tissue-specific alternative splice forms of human genes. We validated our muscle-specific and brain-specific splice forms for known genes. A high fraction (8/10) were reported to have a matching tissue specificity by independent studies in the published literature. The number of tissue-specific alternative splice forms is highest in brain, while eye-retina, muscle, skin, testis and lymph have the greatest enrichment of tissue-specific splicing. Overall, 10-30% of human alternatively spliced genes in our data show evidence of tissue-specific splice forms. Seventy-eight percent of our tissue-specific alternative splices appear to be novel discoveries. We present bioinformatics analysis of several tissue-specific splice forms, including automated protein isoform sequence and domain prediction, showing how our data can provide valuable insights into gene function in different tissues. For example, we have discovered a novel kidney-specific alternative splice form of the WNK1 gene, which appears to specifically disrupt its N-terminal kinase domain and may play a role in PHAII hypertension. Our database greatly expands knowledge of tissue-specific alternative splicing and provides a comprehensive dataset for investigating its functional roles and regulation in different human tissues.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alternative Splicing / genetics*
  • Amino Acid Sequence
  • Brain / metabolism
  • Computational Biology / statistics & numerical data
  • DNA-Binding Proteins / genetics
  • Expressed Sequence Tags
  • Female
  • Gene Expression Profiling
  • Gene Library
  • Genome, Human*
  • Humans
  • Interferon Regulatory Factor-3
  • Male
  • Molecular Sequence Data
  • Protein Isoforms / genetics
  • Sequence Homology, Amino Acid
  • Transcription Factors / genetics
  • Transcription, Genetic / genetics*
  • cdc42 GTP-Binding Protein / genetics


  • DNA-Binding Proteins
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Protein Isoforms
  • Transcription Factors
  • cdc42 GTP-Binding Protein