title: Splice-mediated insertion of an Alu sequence inactivates ornithine delta-aminotransferase: a role for Alu elements in human mutation.
abstract: In studies of mutations causing deficiency of ornithine delta-aminotransferase (EC 2.6.1.13), we found an allele whose mature mRNA has a 142-nucleotide insertion at the junction of sequences from exons 3 and 4. The insert derives from an Alu element in ornithine delta-aminotransferase intron 3 oriented in the direction opposite to transcription (an "antisense Alu"). A guanine----cytosine transversion creates a donor splice site in this Alu, activating a cryptic acceptor splice site at its 5' end and causing splice-mediated insertion of an Alu fragment into the mature ornithine-delta-aminotransferase mRNA. We note that the complement of the Alu consensus sequence has at least two cryptic acceptor sites and several potential donor sequences and predict that similar mutations will be found in other genes.
authors.affiliation: Service de Génétique Médicale, Hôpital Ste-Justine, Montreal, Canada.
authors.forename: G A
authors.initials: GA
authors.lastname: Mitchell
authors.forename: D
authors.initials: D
authors.lastname: Labuda
authors.forename: G
authors.initials: G
authors.lastname: Fontaine
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: J P
authors.initials: JP
authors.lastname: Bonnefont
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
authors.forename: L C
authors.initials: LC
authors.lastname: Brody
authors.forename: G
authors.initials: G
authors.lastname: Steel
authors.forename: C
authors.initials: C
authors.lastname: Obie
authors.forename: D
authors.initials: D
authors.lastname: Valle
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D015342:DNA Probes; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D015345:Oligonucleotide Probes; D009953:Ornithine-Oxo-Acid Transaminase / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D010375:Pedigree; D010957:Plasmids; D016133:Polymerase Chain Reaction / Q000379:methods; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D012867:Skin / Q000201:enzymology
chemical_list: D015342:DNA Probes; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D009953:Ornithine-Oxo-Acid Transaminase