Understanding the significance of somatic mutations requires knowledge of the mutations that occur in vivo in healthy people.
The molecular characterization of mutations in the hypoxanthine phosphoribosyltransferase (hprt) gene in 217 independent T-lymphocyte mutants from 172 donors, including smoking and non-smoking males and females, reveals a broad spectrum of in vivo somatic mutation occurring in a population of healthy people.
Identification of the DNA alteration in individual mutant clones was accomplished using either one or a combination of multiplex polymerase chain reaction analysis of genomic DNA, sequencing of cDNA, and genomic DNA sequencing.
The total spectrum consists of 59% (128/217) base substitutions :
126 simple and two tandem CC>TT base substitutions ;
39% (85/217) deletion/insertion type mutations : 30 frameshifts, 26 small (3-200 basepairs) and 27 large deletions, and two duplications ;
and the remaining 2% (4/217) complex mutations involving the deletion of one to 11 basepairs which are replaced by 1 to 10 basepairs.
No significant difference was detected between the base substitution spectra for the smokers and the non-smokers.
Analysis of the number of mutations occurring at any one base position led to the identification of three hotspots for mutations at basepairs 197,508 and 617, in the hprt gene coding region. (...)
Mots-clés Pascal : Hypoxanthine phosphoribosyltransferase, Pentosyltransferases, Glycosyltransferases, Transferases, Enzyme, Mutation somatique, Gène, Homme, Normal, Epidémiologie, Lymphocyte T, Tabagisme, Sexe, Age, Séquence nucléotide, Gène hprt, Gène reporter
Mots-clés Pascal anglais : Hypoxanthine phosphoribosyltransferase, Pentosyltransferases, Glycosyltransferases, Transferases, Enzyme, Somatic mutation, Gene, Human, Normal, Epidemiology, T-Lymphocyte, Tobacco smoking, Sex, Age, Nucleotide sequence
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 96-0437394
Code Inist : 002A07E03. Création : 10/04/1997.