ASHESdb - Alternatively Spliced Human genes by Exon Skipping - A Database

 

 

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Introduction

Alternative splicing is the major contributor to protein diversity in human. Some genes can generate as many as thousand protein isoforms by alternative splicing. The mechanism of alternative splicing in normal and diseased states is perplexing. Differential joining of exons during alternative splicing is important in detecting genetic disorders. Alternative splicing is reported to regulate the sub-cellular localization of divalent metal transporter 1 isoforms and the NMDA R1 receptor gene. Therefore, a comprehensive knowledge on alternative splicing (mechanism and combinatorial protein diversity) is critical in efficient gene discovery and target validation. Alternative splicing can change the mRNA product in several ways. At its simplest level, an exon can be removed (exon skip), lengthened or shortened (alternative 5' or 3' splicing).

However, identification of splice variants remains tricky and arduous mainly due to large intervening sequences and lack of tissue specific cDNA sequence data. As can be seen majority of currently known splice variants are identified using EST and EST coverage in the protein coding sequence of many genes is still inadequate to predict splicing to a large extent. Moreover, there are limitations in accuracy resulting from the single-pass sequencing that has been used to identify ESTs. In this database, we describe alternatively spliced (exon skipping) human genes identified strictly using full-length cDNA sequences (MGC). This novel approach makes the detection of splice variants more reliable and accurate. This circumvents the greatest challenges in using EST databases to understand alternative splicing and thereby facilitates the task of comprehending the relationships of these short EST sequences to each other and to other genes.

The database integrates a variety of data for each gene ranging from gene map, gene structure, splice variants and tissue information. Information on mouse orthologs showing exon-skipping patterns for these genes is also provided. This database can be used to study the impact of alternative splicing on protein function and could be a useful resource to researchers who have found a new cDNA or human gene and wish to find additional information.