How common are common fragile sites in humans: interindividual variation in the distribution of aphidicolin-induced fragile sites

Abstract

To obtain an estimate of the variation in common fragile sites (CFSs) among individuals, aphidicolin (APC)-induced chromosomal breakage data were analyzed for 20 karyotypically normal adult humans. As it is specifically designed to meet the analytical requirements for considering fragile sites as presence/absence characters in single individuals, the FSM methodology (Böhm et al., 1995) was used to statistically distinguish fragile from nonfragile sites. These analyses indicated that the APC-induced fragile sites are not ubiquitous but vary extensively among individuals; the per-individual number of fragile sites ranged from as few as seven to as many as 20. Of the 45 different sites identified as fragile, 19 (42%) occurred in more than half of the individuals, but only two sites (3p14 and 16q23) were fragile in all of the individuals; 12 (27% of the total) were fragile in single individuals only. Although these analyses provide statistical confirmation (and initial estimates of population variation) for 43 of the 88 APC-inducible fragile sites currently recognized as occurring among humans, they are consistent with the hypothesis that many of the currently recognized human CFSs have been erroneously identified. These results indicate the need for per-individual statistical identification of CFSs for larger samples of individuals and that studies of particular fragile sites should be conducted on individuals documented to be fragile at the loci under consideration.