Discovery of tissue-specific exons using comprehensive human exon microarrays

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. We have designed a high-density oligonucleotide microar...

Full description

Saved in:
Bibliographic Details
Published in:Genome biology 2007-01, Vol.8 (4), p.R64-R64
Main Authors: Clark, Tyson A, Schweitzer, Anthony C, Chen, Tina X, Staples, Michelle K, Lu, Gang, Wang, Hui, Williams, Alan, Blume, John E
Format: Article
Language:English
Subjects:
Algorithms
Alternative Splicing
Brain - metabolism
Exons
Gene Expression Profiling
Humans
Oligonucleotide Array Sequence Analysis - methods
RNA, Messenger - metabolism
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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.
ISSN:1465-6906
1474-760X
1465-6914
DOI:10.1186/gb-2007-8-4-r64