EURASNET and medical research

Around 15% of all point mutations causing human genetic disease either create or disrupt canonical splice sites. In addition, genetic analysis in several gene systems has shown that many genomic substitutions, not positioned in canonical sites and previously classified as neutral or missense, have been subsequently found to affect the splicing process.

These studies emphasise our incomplete knowledge of the molecular mechanisms involved in splicing, which limits the development of new strategies for correcting splicing defects. In addition to disease causing mutations in selected genes, changes in alternative splicing patterns are also associated with a range of diseases including some degenerative diseases, cancer and HIV. In some cases changes in alternative splicing patterns occur without obvious mutation of the affected genes. These alternative splicing modifications are potentially associated with changes in trans-acting splicing factors.

Understanding molecular mechanisms of splicing regulation in the cellular context, and understanding global regulatory networks, will have a fundamental impact on our understanding of the causes of many diseases and the design of new therapeutic strategies.

Important strategic objectives of EURASNET in pathological splicing are:

• the identification of aberrant splicing in human disease
• the characterisation of different regulatory elements, splicing factors and molecular mechanisms involved in the normal splicing and aberrant splicing of specific genes
• the development of new molecular therapies from research in the fields of chemical biology and other enabling technologies.

EURASNET also aims to strengthen contacts with European medical-genetics groups and diagnostics development.