COMPUTATIONAL INVESTIGATION OF ALTERNATIVE SPLICING AND TISSUE-SPECIFIC GENE EXPRESSION IN DISEASE-RELATED GENES: A COMBINATORIAL CONTROL OF PROTEIN DIVERSITY AND REGULATION

Although the sequence of the human genome can be considered virtually complete, we are still very far from having an ultimate inventory of the genes it contains. The most recent studies estimate that the actual number of human genes should range between 20,000 and 25,000, strikingly lower than the original estimates of 40,000 or even 100,000 genes. On the other hand, it seems that the number of proteins expressed (produced) in humans is much higher than expected (more than 100,000), and thus much higher than the estimated gene count itself. The explanation for this apparent contradiction lies in alternative splicing mechanisms, which are more widespread than expected, and cause the same gene to produce different transcripts (RNAs), and thus ultimately different proteins. In this research project we plan to study the alternative splicing of genes involved in neuromuscular diseases with the aim of obtaining a more thorough description of their expression at transcript and protein level, and at the same time, to identify non coding regions of the genome involved in the regulation of gene expression and alternative splicing. It is straightforward to see how reaching a deeper understanding of the genetic repertoire and expression profile of healthy and diseased cells is a fundamental step in the development of therapeutic strategies against neuromuscular genetic diseases.