title: Contemporary retrotransposition of a novel non-coding gene induces exon-skipping in dystrophin mRNA.
abstract: Non-autonomous retrotransposon-mediated mobilizations of the Alu family are known pathogenic mechanisms of human disease. Here, we report a pathogenic, contemporary, non-autonomous retrotransmobilization of part of a novel non-coding gene into the dystrophin gene. In a Japanese Duchenne muscular dystrophy patient, a 330-bp-long de novo insertion was identified in exon 67 of dystrophin. The insertion induced exon 67-skipping in the dystrophin mRNA, creating a premature stop codon. The sequence of the insertion had certain characteristics of retrotransposons: an antisense polyadenylation signal accompanied by a poly(T) sequence and a target site duplication. The insertion site matched the consensus recognition sequence for the L1 endonuclease, indicating a retrotransposon-mediated event, although the inserted sequence did not match any known retrotransposons. The origin of the inserted sequence was mapped to a gene-poor region of chromosome 11. The inserted fragment was expressed in multiple human tissue RNAs, indicating that it is a novel transcript. The full length of the transcript was cloned and showed no meaningful protein coding ability.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kobe University, 7-5-1 Kusunokicho, Chuo, Kobe, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Awano
authors.forename: Rusdy Ghazali
authors.initials: RG
authors.lastname: Malueka
authors.forename: Mariko
authors.initials: M
authors.lastname: Yagi
authors.forename: Yo
authors.initials: Y
authors.lastname: Okizuka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics; D016189:Dystrophin / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D016254:Mutagenesis, Insertional; D026723:Polyadenylation; D012333:RNA, Messenger / Q000235:genetics*; D018626:Retroelements / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D016189:Dystrophin; D012333:RNA, Messenger; D018626:Retroelements