These and other related questions were addressed at the ‘Splicing and genetic diseases’ workshop, sponsored by the European Alternative Splicing Network (EURASNET, www.eurasnet.info) in Paris, 1–2 October 2009, which brought together the worlds of clinical molecular geneticists and basic researchers working on alternative splicing.

The conference discussed examples of UVs detected in molecular diagnostic activities on several genes involved in mendelian diseases, such as neurofibromatosis type 1 and tuberous sclerosis (Diana Baralle), spinal muscular atrophy (Alexandra Martins, Rouen), susceptibility to breast/ovarian cancers (Claude Houdayer, Paris; Sylvie Mazoyer, Lyon), hereditary colon cancers (Mario Tosi), Usher syndrome and Duchenne and Becker muscular dystrophy (Sylvie Tuffery-Giraud, Montpellier), and cystic fibrosis (Abdel Aissad and Pascale Fanen, Créteil, France). The examples showed that the effect of mutations within the splice sites could be predicted rather accurately. However, predicting the possible effects on splicing of UVs located at deep intronic positions or at internal positions of exons can be very difficult. Exonic UVs can affect splicing-regulatory elements and induce splicing defects instead of, or in addition to, producing functionally relevant protein changes. It is therefore currently not possible to set general guidelines for predicting the effects of UVs on splicing, and functional assays are necessary to validate bioinformatics predictions or to improve them.

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