Linked Life Data

9308370

Source:http://linkedlifedata.com/resource/pubmed/id/9308370

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1997-10-23
pubmed:abstractText
Rapid progress in DNA technology has entailed the possibility of readily detecting mutations in disease genes. In contrast to this, techniques to characterize the effects of mutations are still very time consuming. It has turned out that many of the mutations detected in disease genes are missense mutations. Characterization of the effect of these mutations is particularly important in order to establish that they are disease causing and to estimate their severity. We use the experiences with investigation of medium-chain acyl-CoA dehydrogenase deficiency as an example to illustrate that (i) impaired folding is a common effect of missense mutations occurring in genetic diseases, (ii) increasing the level of available chaperones may augment the level of functional mutant protein in vivo, and (iii) one mutation may have multiple effects. The interplay between the chaperones assisting folding and proteases that attack folding intermediates is decisive for how large a proportion of a mutant polypeptide impaired in folding acquires the functional structure. This constitutes a protein quality control system, and the handling of a given mutant protein by this system may vary due to environmental conditions or genetic variability in its components. The possibility that intraindividual differences in the handling of mutant proteins may be a mechanism accounting for phenotypic variability is discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0079-6603
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
301-37
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Impaired folding and subunit assembly as disease mechanism: the example of medium-chain acyl-CoA dehydrogenase deficiency.
pubmed:affiliation
Center for Medical Molecular Biology, Aarhus University Hospital, Denmark.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't