title: Discovery of tissue-specific exons using comprehensive human exon microarrays.
abstract: BACKGROUND
  Higher eukaryotes express a diverse population of messenger RNAs generated by alternative splicing. Large-scale methods for monitoring gene expression must adapt in order to accurately detect the transcript variation generated by this splicing.
  
  
  RESULTS
  We have designed a high-density oligonucleotide microarray with probesets for more than one million annotated and predicted exons in the human genome. Using these arrays and a simple algorithm that normalizes exon signal to signal from the gene as a whole, we have identified tissue-specific exons from a panel of 16 different normal adult tissues. RT-PCR validation confirms approximately 86% of the predicted tissue-enriched probesets. Pair-wise comparisons between the tissues suggest that as many as 73% of detected genes are differentially alternatively spliced. We also demonstrate how an inclusive exon microarray can be used to discover novel alternative splicing events. As examples, 17 new tissue-specific exons from 11 genes were validated by RT-PCR and sequencing.
  
  
  CONCLUSIONS
  In conjunction with a conceptually simple algorithm, comprehensive exon microarrays can detect tissue-specific alternative splicing events. Our data suggest significant expression outside of known exons and well annotated genes and a high frequency of alternative splicing events. In addition, we identified and validated a number of novel exons with tissue-specific splicing patterns. The tissue map data will likely serve as a valuable source of information on the regulation of alternative splicing.
authors: Affymetrix, Inc, Santa Clara, CA 95051, USA. tyson_clark@affymetrix.com
authors: Tyson A
authors: TA
authors: Clark
authors: Anthony C
authors: AC
authors: Schweitzer
authors: Tina X
authors: TX
authors: Chen
authors: Michelle K
authors: MK
authors: Staples
authors: Gang
authors: G
authors: Lu
authors: Hui
authors: H
authors: Wang
authors: Alan
authors: A
authors: Williams
authors: John E
authors: JE
authors: Blume
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing; D001921:Brain / Q000378:metabolism; D005091:Exons; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger