It has been suggested that one third of all disease-causing mutations impact on splicing. Common errors include:
*Mutation of a splice site resulting in loss of function of that site. Results in exposure of a premature stop codon, loss of an exon, or inclusion of an intron.
*Mutation of a splice site reducing specificity. May result in variation in the splice location, causing insertion or deletion of amino acids, or most likely, a disruption of the reading frame.
*Displacement of a splice site, leading to inclusion or exclusion of more RNA than expected, resulting in longer or shorter exons.
Although many splicing errors are safeguarded by a cellular quality control mechanism termed nonsense-mediated mRNA decay (NMD), a number of splicing-related diseases also exist, as suggested above.
Allelic differences in mRNA splicing are likely to be a common and important source of phenotypic diversity at the molecular level, in addition to their contribution to genetic disease susceptibility. Indeed, genome-wide studies in humans have identified a range of genes that are subject to allele-specific splicing.
In plants, variation for flooding stress tolerance correlated with stress-induced alternative splicing of transcripts associated with gluconeogenesis and other processes.