Variable deletion of exon 9 coding sequences in cystic fibrosis transmembrane conductance regulator gene mRNA transcripts in normal bronchial epithelium

C. S. Chu, B. C. Trapnell, J. J. Murtagh, J. Moss, W. Dalemans, S. Jallat, A. Mercenier, A. Pavirani, J. P. Lecocq, G. R. Cutting, W. B. Guggino, Ronald Crystal

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

The predicted protein domaibs 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 ≤ 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.

Original languageEnglish
Pages (from-to)1355-1363
Number of pages9
JournalEMBO Journal
Volume10
Issue number6
Publication statusPublished - 23 May 1991
Externally publishedYes

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Regulator Genes
Exons
Epithelium
Genes
Messenger RNA
Introns
RNA Splice Sites
Alleles

Keywords

  • cystic fibrosis
  • epithelium
  • human
  • lung
  • mRNA
  • splicing

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Variable deletion of exon 9 coding sequences in cystic fibrosis transmembrane conductance regulator gene mRNA transcripts in normal bronchial epithelium. / Chu, C. S.; Trapnell, B. C.; Murtagh, J. J.; Moss, J.; Dalemans, W.; Jallat, S.; Mercenier, A.; Pavirani, A.; Lecocq, J. P.; Cutting, G. R.; Guggino, W. B.; Crystal, Ronald.

In: EMBO Journal, Vol. 10, No. 6, 23.05.1991, p. 1355-1363.

Research output: Contribution to journalArticle

Chu, CS, Trapnell, BC, Murtagh, JJ, Moss, J, Dalemans, W, Jallat, S, Mercenier, A, Pavirani, A, Lecocq, JP, Cutting, GR, Guggino, WB & Crystal, R 1991, 'Variable deletion of exon 9 coding sequences in cystic fibrosis transmembrane conductance regulator gene mRNA transcripts in normal bronchial epithelium', EMBO Journal, vol. 10, no. 6, pp. 1355-1363.
Chu, C. S. ; Trapnell, B. C. ; Murtagh, J. J. ; Moss, J. ; Dalemans, W. ; Jallat, S. ; Mercenier, A. ; Pavirani, A. ; Lecocq, J. P. ; Cutting, G. R. ; Guggino, W. B. ; Crystal, Ronald. / Variable deletion of exon 9 coding sequences in cystic fibrosis transmembrane conductance regulator gene mRNA transcripts in normal bronchial epithelium. In: EMBO Journal. 1991 ; Vol. 10, No. 6. pp. 1355-1363.
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abstract = "The predicted protein domaibs 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 ≤ 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.",
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AU - Moss, J.

AU - Dalemans, W.

AU - Jallat, S.

AU - Mercenier, A.

AU - Pavirani, A.

AU - Lecocq, J. P.

AU - Cutting, G. R.

AU - Guggino, W. B.

AU - Crystal, Ronald

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N2 - The predicted protein domaibs 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 ≤ 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.

AB - The predicted protein domaibs 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 ≤ 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.

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