Nucleic Acids Research, 2002, Vol. 30, No. 17 3754-3766
© 2002 Oxford University Press
Genome-wide detection of tissue-specific alternative splicing in the human transcriptome
Molecular Biology Institute and Department of Chemistry and Biochemistry, University of California–Los Angeles, Los Angeles, CA 90095-1570, USA
*To whom correspondence should be addressed. Tel: +1 310 825 7374; Fax: +1 310 267 0248; Email: leec{at}mbi.ucla.edu
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.
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