Linked Life Data

8456808

Source:http://linkedlifedata.com/resource/pubmed/id/8456808

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1993-4-22
pubmed:abstractText
We discuss the definition of mutations in osteogenesis imperfecta (OI) using a chemical cleavage method for detecting mismatched bases in patient mRNA: control cDNA heteroduplexes. The method is based on the increased chemical modification of cytosines (Cs) by hydroxylamine and thymines (Ts) by osmium tetroxide when they are not paired with their complementary base. The DNA is then cleaved at the modified base with piperidine and the use of radioactively labeled DNA probes allows the position of the mismatched base to be determined by electrophoresis of the cleavage-product. The precise mutations are then determined by specific amplification and sequencing of the region containing the mismatched base. In perinatally lethal OI (OI type II) mismatches have been detected in all 17 cases studied; 12 of these have been fully characterized. In 7 of these 12 cases the mismatches were point mutations in the genes for pro alpha 1(I) or pro alpha 2(I) which resulted in glycine substitutions in the triple helical region of the protein. Sequence variation was detected in addition to the glycine substitutions in 2 cases. In 2 cases the RNA mismatch resulted from changes in the amino acid sequence of the C-propeptide domain. In the 3 remaining cases the mismatch resulted from silent nucleotide sequence variants. In the less severe forms of OI we have studied, mismatches have been detected and characterized in 8 of 12 cases. In 4 of these 8 cases the mismatch resulted from presumably neutral sequence variation and in the other 4 cases mutations have been defined.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0148-7299
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
233-40
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Chemical cleavage method for the detection of RNA base changes: experience in the application to collagen mutations in osteogenesis imperfecta.
pubmed:affiliation
Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't