Somatic Mutations and Aging : Methods for Molecular Analysis of HPRT Mutations

The increasing information on the specific DNA sequence alterations that occur in mutated genes of human somatic cells has allowed the establishment of mutational spectra. Endogenous and exogenous exposures as well as individual susceptibility factors seem to contribute to the complexity of mutational spectra. The X-linked HPRT (hypoxanthine phosphoribosyl transferase) gene in human T lymphocytes has been considered as a suitable target for studying somatic in vivo mutations (1), including those related to aging. The mutant frequency in adults is 10-fold higher than that in newborns and the proportion of point mutations is also considerably higher in adults (90% vs 20%), possibly as results of accumulation of point mutations induced later in life and dilution of the V(D)J-recombinase-mediated spontaneous deletions observed in newborns (2). A significant age-related increase of HPRT mutant frequency (1-3%/yr) has been reported in most studies, with a more rapid increase in smokers compared to nonsmokers (reviewed in ref. 1).