Discovering Association between Alternative Splicing and Disease

[[abstract]]Alternative splicing is important because more proteins can be made from the relative few genes and. it is also an important mechanism regulating genetic expression. In this thesis, we will try to find out alternative splicing isoforms specific to several cancers and schizophenia and different development stage. The integrated information about diseases, pathways, proteins, and alternative splicing will be present. Methods: Alternative splicing database were constructed by aligning EST to whole genomic sequence using multi-layer unique marker methods. Each splicing site will be queried for their EST expression frequency in specific disease or development stage by the specific splicing isoforms. Significance were tested with Fish?s exact test. Using the position in the contig, splicing site was link to their correlated pretein, gene. By linking the same gene, disease information in OMIM and pathway information in KEGG were integrated. Results: 1263 disease specific splicing sites were identified. 63 exon skipping sites and 231 intron retain sites were correlated with hepatoma. 17 sites were correlated with schizophrenia. 163 splicing site were specific to fetal and infantile development stage. Discussion: Further laboratory investigation will be needed for confirming the real significant splicing site clinically