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Article: Low basal transcription of genes for tissue-specific collagens by fibroblasts and lymphoblastoid cells: Application to the characterization of a glycine 997 to serine substitution in α1(II) collagen chains of a patient with spondyloepiphyseal dysplasia

TitleLow basal transcription of genes for tissue-specific collagens by fibroblasts and lymphoblastoid cells: Application to the characterization of a glycine 997 to serine substitution in α1(II) collagen chains of a patient with spondyloepiphyseal dysplasia
Authors
Issue Date1991
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1991, v. 266 n. 19, p. 12487-12494 How to Cite?
AbstractCultured dermal fibroblasts were shown, using amplification of cDNA by the polymerase chain reaction, to produce very low levels of spliced transcripts from the COL2A1 gene that encodes the cartilage-specific α1(II) chains of type II collagen. Cultured lymphoblastoid cells were also shown to produce very low levels of spliced transcripts from the COL1A1 and COL1A2 genes that encode the α1(I) and α2(I) chains of type I collagen, the COL2A1 gene that encodes type II collagen, and the COL3A1 gene that encodes the α1(III) chains of type III collagen. Amplified cDNAs prepared from lymphoblastoid cells were used to identify previously characterized heterozygous mutations in the COL1A1 and COL1A2 genes from two patients with osteogenesis imperfecta and in the COL3A1 gene from a patient with the Ehlers-Danlos syndrome type IV. Amplified α1(II) cDNA from fibroblasts and lymphoblastoid cells of a child with spondyloepiphyseal dysplasia congenita was also used to localize sequence mismatches using chemical modification of cDNA:cDNA heteroduplexes by hydroxylamine and cleavage with piperidine. The amplification products containing the mismatched region were sequenced and the mutation was shown to change the codon GGC for glycine 997 to AGC for serine in the triple helical domain of the α1(II) chains. The corresponding region of the genomic DNA was sequenced and the heterozygous point mutation was shown to be in exon 48 of the COL2A1 gene. Allelic restriction mapping showed that neither parent carried the mutation in their leucocytes. This mutation emphasizes the importance of COL2A1 mutations in producing the spondyloepiphyseal dysplasia phenotype. The low basal rate of transcription (''illegitimate transcription''), splicing, and polyadenylation of tissue-specific mRNAs by cultured dermal fibroblasts and lymphoblastoid cells provides the opportunity to localize and sequence mutations in amplified cDNA in patients from whom affected tissue is unavailable.
Persistent Identifierhttp://hdl.handle.net/10722/147357
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, Den_US
dc.contributor.authorCole, WGen_US
dc.date.accessioned2012-05-29T06:03:09Z-
dc.date.available2012-05-29T06:03:09Z-
dc.date.issued1991en_US
dc.identifier.citationJournal Of Biological Chemistry, 1991, v. 266 n. 19, p. 12487-12494en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/147357-
dc.description.abstractCultured dermal fibroblasts were shown, using amplification of cDNA by the polymerase chain reaction, to produce very low levels of spliced transcripts from the COL2A1 gene that encodes the cartilage-specific α1(II) chains of type II collagen. Cultured lymphoblastoid cells were also shown to produce very low levels of spliced transcripts from the COL1A1 and COL1A2 genes that encode the α1(I) and α2(I) chains of type I collagen, the COL2A1 gene that encodes type II collagen, and the COL3A1 gene that encodes the α1(III) chains of type III collagen. Amplified cDNAs prepared from lymphoblastoid cells were used to identify previously characterized heterozygous mutations in the COL1A1 and COL1A2 genes from two patients with osteogenesis imperfecta and in the COL3A1 gene from a patient with the Ehlers-Danlos syndrome type IV. Amplified α1(II) cDNA from fibroblasts and lymphoblastoid cells of a child with spondyloepiphyseal dysplasia congenita was also used to localize sequence mismatches using chemical modification of cDNA:cDNA heteroduplexes by hydroxylamine and cleavage with piperidine. The amplification products containing the mismatched region were sequenced and the mutation was shown to change the codon GGC for glycine 997 to AGC for serine in the triple helical domain of the α1(II) chains. The corresponding region of the genomic DNA was sequenced and the heterozygous point mutation was shown to be in exon 48 of the COL2A1 gene. Allelic restriction mapping showed that neither parent carried the mutation in their leucocytes. This mutation emphasizes the importance of COL2A1 mutations in producing the spondyloepiphyseal dysplasia phenotype. The low basal rate of transcription (''illegitimate transcription''), splicing, and polyadenylation of tissue-specific mRNAs by cultured dermal fibroblasts and lymphoblastoid cells provides the opportunity to localize and sequence mutations in amplified cDNA in patients from whom affected tissue is unavailable.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCollagen - Biosynthesis - Geneticsen_US
dc.subject.meshDna - Geneticsen_US
dc.subject.meshFibroblasts - Metabolismen_US
dc.subject.meshGlycine - Geneticsen_US
dc.subject.meshHeterozygoteen_US
dc.subject.meshHumansen_US
dc.subject.meshLymphocytes - Metabolismen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutationen_US
dc.subject.meshNucleic Acid Heteroduplexesen_US
dc.subject.meshNucleic Acid Hybridizationen_US
dc.subject.meshOsteochondrodysplasias - Genetics - Metabolismen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshRna Splicingen_US
dc.subject.meshRna, Messenger - Genetics - Metabolismen_US
dc.subject.meshRestriction Mappingen_US
dc.subject.meshSerine - Geneticsen_US
dc.subject.meshTranscription, Geneticen_US
dc.titleLow basal transcription of genes for tissue-specific collagens by fibroblasts and lymphoblastoid cells: Application to the characterization of a glycine 997 to serine substitution in α1(II) collagen chains of a patient with spondyloepiphyseal dysplasiaen_US
dc.typeArticleen_US
dc.identifier.emailChan, D:chand@hkucc.hku.hken_US
dc.identifier.authorityChan, D=rp00540en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid1905723-
dc.identifier.scopuseid_2-s2.0-0025743952en_US
dc.identifier.volume266en_US
dc.identifier.issue19en_US
dc.identifier.spage12487en_US
dc.identifier.epage12494en_US
dc.identifier.isiWOS:A1991FV18000062-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChan, D=7402216545en_US
dc.identifier.scopusauthoridCole, WG=7201518727en_US

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