October 09, 2004

The first wave: bioinformatic discovery of alternative splicing from expressed sequences

Alternative splicing is one of the fields in molecular biology that demonstrate bioinformatics can play a leading role in scientific discoveries. It's the bioinformatics analysis of ESTs data in late 90s which showed the striking abundance of alternative splicing in human and most eukaryotic genomes. This stimulated many experimental investigations. Those early bioinformatics work included:

Frequent alternative splicing of human genes. Genome Res. 1999 Dec;9(12):1288-93. Mironov AA, Fickett JW, Gelfand MS.
EST comparison indicates 38% of human mRNAs contain possible alternative splice forms. FEBS Lett. 2000 May 26;474(1):83-6. Brett D, Hanke J, Lehmann G, Haase S, Delbruck S, Krueger S, Reich J, Bork P.
ISIS, the intron information system, reveals the high frequency of alternative splicing in the human genome. Nat Genet. 2000 Apr;24(4):340-1. Croft L, Schandorff S, Clark F, Burrage K, Arctander P, Mattick JS.
Gene structure prediction and alternative splicing analysis using genomically aligned ESTs. Genome Res. 2001 May;11(5):889-900. Kan Z, Rouchka EC, Gish WR, States DJ.
Genome-wide detection of alternative splicing in expressed sequences of human genes. Nucleic Acids Res. 2001 Jul 1;29(13):2850-9. Modrek B, Resch A, Grasso C, Lee C.

These work used ESTs, or Expressed Sequence Tags, to discover alternative splicing. ESTs are fragments of the full length transcripts. The extensive EST sequenceing effort in the 1990s generated large amount of EST data. These EST sequences represent "snapshots" of the transcripts in different tissues, cell types and developmental stages, and are tremendously useful for detecting transcript variations such as Single Nucleotide Polymorphisms (SNPs) and alternative splicing.


This picture is taken from the review by Modrek B and Lee C, which illustrates how to detect alternative splicing using EST data.

Posted by yxing at October 9, 2004 05:21 PM
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