title: Detection of two Alu insertions in the CFTR gene.
abstract: BACKGROUND
  LINE-1 (long interspersed element-1) or L1-mediated retrotransposition is a potent force in human genome evolution and an occasional cause of human genetic disease. Since the first report of two de novo L1 insertions in the F8 gene causing hemophilia A, more than 50 L1-mediated retrotranspositional events have been identified as causing human genetic disease. However, a significant bias has generally militated against the detection of these pathological events at autosomal loci. Based upon this and other observations, we surmised that some previously unresolved cystic fibrosis chromosomes might carry hitherto undetected L1-mediated retrotranspositional insertions at the CFTR locus. This study represents an attempt to identify such mutational events.
  
  
  METHODS
  100 previously unresolved cystic fibrosis chromosomes were carefully reanalyzed using quantitative high-performance liquid chromatography (QHPLC).
  
  
  RESULTS
  Two simple Alu insertions were identified in the CFTR gene, within exons 16 and 17b respectively.
  
  
  CONCLUSIONS
  Our findings have not only revealed a previously unknown mutational mechanism responsible for cystic fibrosis but also represent an important addition to the already diverse spectrum of known CFTR gene mutations. Experience with the CFTR gene suggests that pathological L1-mediated retrotranspositional events may also have been overlooked at other gene loci and should always be considered in cases that appear to be refractory to analysis.
authors.affiliation: INSERM, U613, 29220 Brest, France. Jian-Min.Chen@univ-brest.fr
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Chen
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Masson
authors.forename: Milan
authors.initials: M
authors.lastname: Macek
authors.forename: Odile
authors.initials: O
authors.lastname: Raguénès
authors.forename: Tereza
authors.initials: T
authors.lastname: Piskackova
authors.forename: Brigitte
authors.initials: B
authors.lastname: Fercot
authors.forename: Libor
authors.initials: L
authors.lastname: Fila
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Audrézet
authors.forename: Claude
authors.initials: C
authors.lastname: Férec
mesh_terms: D020087:Alu Elements / Q000235:genetics*; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator