SIMILAR MUTANT FREQUENCIES OBSERVED BETWEEN PAIRS OF MONOZYGOTIC TWINS

The relative contribution of both genetic and environmental factors to spontaneous mutation frequency in humans is unknown. We have investig ated the contribution of genetic factors to this phenomenon by determi ning the in vivo mutant frequency at the hypoxanthine-guanine phosphor ibosyltransferase (hprt) locus in circulating T-lymphocytes obtained f rom pairs of monozygotic twins. hprt mutant frequencies were determine d three times over fourteen days in six sets of monozygotic male twins (mean age 30) taking part in a Russian Space Program inclined bed res t experiment. Blood samples were obtained prior to, during, and immedi ately following the experiment. Mononuclear cells were separated, froz en, and flown to Canada for analysis using the hprt T-lymphocyte clona l assay. There is no evidence within this data set to demonstrate that the period of inclined bed rest to simulate the effects of weightless ness had any effect on the observed mutant frequency. However, the ave rage mutant frequency for the six sets of Russian twins was found to b e three times higher than that of Western counterparts. More surprisin gly, the spontaneous mutant frequency of monozygotic twins was found t o be much more similar within pairs than between pairs of twins. These data suggest that the contribution of genetics in the determination o f mutation frequency is substantial. However, whether high concordance within twin pairs reflects shared environmental experience as well as common genetic factors is not entirely clear. More data will be requi red to distinguish genetic from environmental factors and to determine the degree to which mutant frequency is genetically determined, (C) 1 997 Wiley-Liss, Inc.