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Title: A New Database on Alternative Splice Forms
P120
Pospisil, Heike; Herrmann, Alexander; Reich, Jens

pospisil@mdc-berlin.de, alexander.herrmann@mdc-berlin.de
Max-Delbrueck-Center for Molecular Medicine Berlin, Germany

It is now commonly accepted that for a huge amount of genes the process of alternative splicing yields much more than one protein per gene. It has long been assumed that only five percent of human genes are alternatively spliced. More recent estimates that are based on ESTs mapped onto mRNA sequences indicate a high rate of alternative splicing (up to 60%). It has also become clear that EST coverage results in increasing estimates.
We developed a computational method which allows to detect large numbers of alternative splice forms by comparison with ESTs. Our algorithm defines a possible alternative splice form by comparing high-scoring ESTs to mRNA sequences using BLAST search tool with slightly modified parameters. To identify alternative splicing we use some parameters indicating the percental identity of ESTs to mRNA sequences, the minimal length of the overlapping region, and the minimal length of a gap. Using this method we created a database of novel candidate alternative splice forms.Our database represents splice forms of 9 different organisms (Arabidopsis thaliana, Bos taurus, Caenorhabditis elegans, Danio Rerio, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, and Xenopus laevis) from ESTs and mRNA GenBank sequence records.The database is accessible under http://www.bioinf.mdc-berlin.de/splice/db/.
Moreover we added the database to the Integrated Genetic Map Service (ISMB, http://www.bioinf.mdc-berlin.de/igms/).The IGMS is a comprehensive information system that combines the knowledge from genomic sequence, genetic map and genetic disorders databases. It enables to select mRNA and EST data for complex problems, as. eg.: Finding out all ESTs which are (a) expressed in a defined tissue, (b) allocated to UniGene clusters with at least 30ESTs, (c) overexpressed in cancer and (d) showing at least 2 alternative splice forms.
[1] Brett D, Pospisil H. et al. (2002) Alternative splicing and genome complexity. Nat Genet. 30, 29-30.
[2] Brett D., Kemmner W. et al. (2001) A rapid bioinformatic method identifies novel genes with direct clinical relevance to colon cancer. Oncogene. 20, 4581-5.
[3] Brett D., Hanke J. et al. (2000) EST comparison indicates 38% of human mRNAs contain possible alternative splice forms. FEBS Lett. 474, 83-6.