Variable deletion of exon 9 coding sequences in cystic fibrosis transmembrane conductance regulator gene mRNA transcripts in normal bronchial epithelium - PubMed (original) (raw)
Variable deletion of exon 9 coding sequences in cystic fibrosis transmembrane conductance regulator gene mRNA transcripts in normal bronchial epithelium
C S Chu et al. EMBO J. 1991 Jun.
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.
Comment in
- Cystic fibrosis transmembrane conductance regulator (CFTR) gene transcripts.
Harris A. Harris A. EMBO J. 1992 Jan;11(1):379-80. doi: 10.1002/j.1460-2075.1992.tb05061.x. EMBO J. 1992. PMID: 1371251 Free PMC article. No abstract available.
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References
- Trends Biochem Sci. 1990 Nov;15(11):430-4 - PubMed
- J Mol Biol. 1975 Nov 5;98(3):503-17 - PubMed
- Cell. 1991 Jan 11;64(1):181-7 - PubMed
- Nature. 1990 Nov 8;348(6297):110-1 - PubMed
- Cell. 1990 Nov 16;63(4):827-34 - PubMed
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