Linked Life Data

1306134

Source:http://linkedlifedata.com/resource/pubmed/id/1306134

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1993-8-5
pubmed:abstractText
Molecular characterization of in vivo mutation at the human hypoxanthine phosphoribosyltransferase (hprt) locus has revealed a broad spectrum of mutation, both with regard to germ-line mutation in Lesch-Nyhan and gout patients, and somatic mutation in 6-thioguanine resistant T-lymphocytes from healthy individuals. The pattern of missense mutation shows a non-random distribution with a preferential location to codons for amino acids which are identical in human and the two parasites Schistosoma mansoni and Plasmodium falciparum. Although these 'evolutionary conserved' amino acids account for only 32% of the amino acids in the human hprt protein, they are involved in 76% of the missense mutations at the hprt locus in human T-lymphocytes, 67% in Lesch-Nyhan patients (with severe hprt-deficiency), but only 43% in gout patients (with partial hprt deficiency). This observation supports the notion that evolutionary conserved amino acids constitute functionally important sites in the hprt enzyme, and missense mutations affecting these amino acids will often lead to complete loss of enzyme activity. Substitutions of 'non-conserved' amino acids cause less severe hprt-deficiency (as seen in the gout patients), or may even escape clinical diagnosis. These considerations are important for the understanding of structure-activity relationships in the hprt protein, possible differences between hprt mutational spectra in germ-line and somatic cells, and the mutational spectra induced by specific exogeneous mutagens.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0960-314X
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:geneSymbol
hprt
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
329-36
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Missense mutations and evolutionary conserved amino acids at the human hypoxanthine phosphoribosyl-transferase locus.
pubmed:affiliation
Environmental Medicine Unit, Karolinska Institutet, Huddinge, Sweden.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't