title: Predicting severity of haemophilia A and B splicing mutations by information analysis.
abstract: Bleeding symptoms and clotting activity vary among mutations that alter mRNA splicing of either the factor VIII or factor IX genes. We analyzed splicing mutations in both genes for changes in individual information (R(i), in bits) involving both donor or acceptor sites. Mutations with low or negative R(i) values (<2.4 bits) or significant changes in R(i) (DeltaR(i) > or = 7 bits) exhibited either reduced protein activity, increased clotting time and bleeding frequency and were predictive of severe disease. Thus, information analysis of splicing mutations may be useful in predicting phenotypes in hemophilia.
authors.affiliation: Department of Cardiology, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: von Kodolitsch
authors.forename: J
authors.initials: J
authors.lastname: Berger
authors.forename: P K
authors.initials: PK
authors.lastname: Rogan
mesh_terms: D005164:Factor IX / Q000235:genetics; D005169:Factor VIII / Q000235:genetics; D006467:Hemophilia A / Q000235:genetics*; D002836:Hemophilia B / Q000235:genetics*; D006801:Humans; D007257:Information Theory; D009154:Mutation; D010641:Phenotype; D022821:RNA Splice Sites; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D022821:RNA Splice Sites; D012333:RNA, Messenger; D005169:Factor VIII; D005164:Factor IX