title: Variable deletion of exon 9 coding sequences in cystic fibrosis transmembrane conductance regulator gene mRNA transcripts in normal bronchial epithelium.
abstract: The predicted protein domains coded by exons 9-12 and 19-23 of the 27 exon cystic fibrosis transmembrane conductance regulator (CFTR) gene contain two putative nucleotide-binding fold regions. Analysis of CFTR mRNA transcripts in freshly isolated bronchial epithelium from 12 normal adult individuals demonstrated that all had some CFTR mRNA transcripts with exon 9 completely deleted (exon 9- mRNA transcripts). In most (9 of 12), the exon 9- transcripts represented less than or equal to 25% of the total CFTR transcripts. However, in three individuals, the exon 9- transcripts were more abundant, comprising 39, 62 and 66% of all CFTR transcripts. Re-evaluation of the same individuals 2-4 months later showed the same proportions of exon 9- transcripts. Of the 24 CFTR alleles in the 12 individuals, the sequences of the exon-intron junctions relevant to exon 9 deletion (exon 8-intron 8, intron 8-exon 9, exon 9-intron 9, and intron 9-exon 10) were identical except for the intron 8-exon 9 region sequences. Several individuals had varying lengths of a TG repeat in the region between splice branch and splice acceptor consensus sites. Interestingly, one allele in each of the two individuals with 62 and 66% exon 9- transcripts had a TT deletion in the splice acceptor site for exon 9. These observations suggest either the unlikely possibility that sequences in exon 9 are not critical for the functioning of the CFTR or that only a minority of the CFTR mRNA transcripts need to contain exon 9 sequences to produce sufficient amounts of a normal CFTR to maintain a normal clinical phenotype.
authors.affiliation: Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: C S
authors.initials: CS
authors.lastname: Chu
authors.forename: B C
authors.initials: BC
authors.lastname: Trapnell
authors.forename: J J
authors.initials: JJ
authors.lastname: Murtagh
authors.forename: J
authors.initials: J
authors.lastname: Moss
authors.forename: W
authors.initials: W
authors.lastname: Dalemans
authors.forename: S
authors.initials: S
authors.lastname: Jallat
authors.forename: A
authors.initials: A
authors.lastname: Mercenier
authors.forename: A
authors.initials: A
authors.lastname: Pavirani
authors.forename: J P
authors.initials: JP
authors.lastname: Lecocq
authors.forename: G R
authors.initials: GR
authors.lastname: Cutting
mesh_terms: D001483:Base Sequence; D001980:Bronchi / Q000502:physiology*; D003550:Cystic Fibrosis; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004848:Epithelium; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C505032:CFTR protein, human; D008565:Membrane Proteins; D009841:Oligonucleotides; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator