How common are common fragile sites: variation of aphidicolin-induced chromosomal fragile sites in a population of the deer mouse ( Peromyscus maniculatus )

Abstract

Aphidicolin (APC)-induced chromosomal gaps and breaks were analyzed for ten deer mice (Peromyscus maniculatus) from a natural population. The FSM statistical methodology was used to identify fragile sites as chromosomal loci exhibiting significantly non-random numbers of gaps/breaks in each individual and enabled an assessment of variation in fragile sites among the individuals. The individual deer mice exhibited as few as 7 to as many as 19 of the populational total of 34 sites. Two sites were fragile in all individuals and 13 sites were fragile in single individuals only. Defined by populational frequencies of greater than 50%, high-frequency fragile sites constituted 26% of the populational total. Approximately 35% of the total fragile sites were fragile in 20-40% of the population (low-frequency fragile sites) and about 38% were fragile in single individuals only. Analysis of the data pooled over all individuals identified significantly non-random breakage at 80 sites, 47 of which were not identified as fragile in any single individual. It appears, therefore, that fragile site identifications from pooled data have fostered an inflated estimate of the numbers and frequencies of common fragile sites. Comparison of the fragile site and spontaneous breakage (control) data suggest that APC-induced fragile sites represent regions of chromosomes that experience elevated levels of somatic mutation. Additionally, the occurrence of APC-induced fragile sites at or near the interstitial breakpoints of two pericentric-inversion polymorphisms in this population supports the hypothesis that fragile sites experience an increased rate of meiotic chromosomal mutation and are predisposed to undergo phylogenetic rearrangement.

Expression of common fragile sites in two Ceboidea species: Saimiri boliviensis and Alouatta caraya (Primates: Platyrrhini)

“…A low frequency of spontaneous CA was found in SBO specimens (6%), while ACA presented higher levels (30%). Different frequencies of spontaneous breakage have been previously reported in other mammals, ranging from as few as 8% to as many 64% [2,3,38,60,69]. In addition, three spontaneous fragile sites, coincident with induced ones, were found to be significantly damaged in ACA, suggesting that these areas are more susceptible to chromosomal breakage.…”

“…Autosomal fragile sites have been related to the origin of constitutional or cancer rearrangements [23,33,49,61,63] and they can be targets of mutagens and carcinogens [2,3,71]. They have also been associated with chromosomal changes during evolution [6,28,31,38,39].…”

Global screening and extended nomenclature for 230 aphidicolin-inducible fragile sites, including 61 yet unreported ones

“…In this study proband III was CaucasianAsian descent whereas probands I and II were of Caucasian origin. Inter-individual frequency variations in FS-expression were also observed in other mammals like the mouse (28) and also between different tissues (29,30). Although aphidicolin-induced FS were previously studied, for a closer Also shown are FS that were not included in the genome browser but described before.…”

“…FRA17D, this study) some authors (12,24,28) suggested a classification in high (HFFS) and low frequency FS (LFFS). This classification seems to be more reliable than the historical division in common and rare FS.…”

Fragility in the 14q21q translocation region

“…There is also evidence to suggest that common fragile sites are preferred sites of sister chromatid exchange (Glover and Stein, 1987), chromosomal deletion and rearrangement (Glover and Stein, 1988;Wang et al, 1993), gene amplification, (Coquelle et al, 1997), transfected plasmid DNA integration (Rassool et al, 1991) and viral integration (Popescu and DiPaolo, 1990). Although common fragile sites have been hypothesized to experience significantly elevated levels of chromosomal mutation and, therefore, to be predisposed to chromosomal rearrangement Hecht 1984, Craig-Holmes et al, 1987;Miró et al, 1987;Yunis, 1987Yunis, , 1990McAllister and Greenbaum, 1997), there are scant data to support these hypotheses. In this paper we present and discuss evidence for the heritable occurrence of APC-inducibed fragility at the translocation region of a der (14; 21) (p10, p10) translocation chromosome in three related rob(14q21q) translocation carriers.…”