Linked Life Data

1905723

Source:http://linkedlifedata.com/resource/pubmed/id/1905723

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1991-8-7
pubmed:databankReference
pubmed:abstractText
Cultured 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 alpha 1(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 alpha 1(I) and alpha 2(I) chains of type I collagen, the COL2A1 gene that encodes type II collagen, and the COL3A1 gene that encodes the alpha 1(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 alpha 1(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 alpha 1(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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
266
pubmed:geneSymbol
COL1A1, COL1A2, COL2A1, COL3A1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12487-94
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:1905723-Base Sequence, pubmed-meshheading:1905723-Cells, Cultured, pubmed-meshheading:1905723-Collagen, pubmed-meshheading:1905723-DNA, pubmed-meshheading:1905723-Fibroblasts, pubmed-meshheading:1905723-Glycine, pubmed-meshheading:1905723-Heterozygote, pubmed-meshheading:1905723-Humans, pubmed-meshheading:1905723-Lymphocytes, pubmed-meshheading:1905723-Molecular Sequence Data, pubmed-meshheading:1905723-Mutation, pubmed-meshheading:1905723-Nucleic Acid Heteroduplexes, pubmed-meshheading:1905723-Nucleic Acid Hybridization, pubmed-meshheading:1905723-Osteochondrodysplasias, pubmed-meshheading:1905723-Phenotype, pubmed-meshheading:1905723-Polymerase Chain Reaction, pubmed-meshheading:1905723-RNA, Messenger, pubmed-meshheading:1905723-RNA Splicing, pubmed-meshheading:1905723-Restriction Mapping, pubmed-meshheading:1905723-Serine, pubmed-meshheading:1905723-Transcription, Genetic
pubmed:year
1991
pubmed:articleTitle
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 alpha 1(II) collagen chains of a patient with spondyloepiphyseal dysplasia.
pubmed:affiliation
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't