title: Splicing in disease: disruption of the splicing code and the decoding machinery.
abstract: Human genes contain a dense array of diverse cis-acting elements that make up a code required for the expression of correctly spliced mRNAs. Alternative splicing generates a highly dynamic human proteome through networks of coordinated splicing events. Cis- and trans-acting mutations that disrupt the splicing code or the machinery required for splicing and its regulation have roles in various diseases, and recent studies have provided new insights into the mechanisms by which these effects occur. An unexpectedly large fraction of exonic mutations exhibit a primary pathogenic effect on splicing. Furthermore, normal genetic variation significantly contributes to disease severity and susceptibility by affecting splicing efficiency.
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Guey-Shin
authors.initials: GS
authors.lastname: Wang
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Cooper
mesh_terms: D017398:Alternative Splicing; D005091:Exons; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D022821:RNA Splice Sites; D012333:RNA, Messenger