Common fragile sites in man and three closely related primate species

Smeets, Dominique; Klundert, Francy A. J. M. van de

doi:10.1159/000132885

Cited by 48 publications

(34 citation statements)

References 12 publications

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“…In addition to the conservation of CFS expression levels among different mouse strains, we found the same for syntenic regions of the mouse and human genomes. Such conservation was already described for the most frequent human CFSs compared to the genomes of different great apes (Yunis and Soreng 1984;Smeets and van de Klundert 1990). Our data shown in Figure 5 support the conclusion that a conservation is also true for less frequent CFSs.…”

Section: Discussionsupporting

confidence: 88%

“…Cytogenetic CFS mapping studies on murine lymphocytes revealed 19 CFSs defined as chromosome bands with significantly elevated gap/break frequencies that expressed the lesion homozygously as well (Elder and Robinson 1989). Comparative analysis in lymphocyte chromosomes of human, three great apes (chimpanzee, gorilla, orangutan), and a simian monkey species (Macaca fascicularis) has demonstrated that a high percentage of human CFSs were found in the equivalent location on chromosomes of apes/monkeys, although with sometimes significantly different expression frequencies (Yunis and Soreng 1984;Smeets and van de Klundert 1990;Ruiz-Herrera et al 2002). A possible coincidence of CFSs with evolutionarily rearranged sites was also described (Smeets and van de Klundert 1990;RuizHerrera et al 2002).…”

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confidence: 99%

“…Comparative analysis in lymphocyte chromosomes of human, three great apes (chimpanzee, gorilla, orangutan), and a simian monkey species (Macaca fascicularis) has demonstrated that a high percentage of human CFSs were found in the equivalent location on chromosomes of apes/monkeys, although with sometimes significantly different expression frequencies (Yunis and Soreng 1984;Smeets and van de Klundert 1990;Ruiz-Herrera et al 2002). A possible coincidence of CFSs with evolutionarily rearranged sites was also described (Smeets and van de Klundert 1990;RuizHerrera et al 2002). However, considering only the most breakage-prone sites of each primate, very few appeared to correspond to a synteny break (SB).…”

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confidence: 99%

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Common fragile sites are conserved features of human and mouse chromosomes and relate to large active genes

Helmrich

Stout-Weider²,

Hermann³

et al. 2006

Genome Res.

100

101

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Common fragile sites (CFSs) are seen as chromosomal gaps and breaks brought about by inhibition of replication, and it is thought that they cluster with tumor breakpoints. This study presents a comprehensive analysis using conventional and molecular cytogenetic mapping of CFSs and their expression frequencies in two mouse strains, BALB/c and C57BL/6, and in human probands. Here we show that induced mouse CFSs relate to sites of spontaneous gaps and breaks and that CFS expression levels in chromosome bands are conserved between the two mouse strains and between syntenic mouse and human DNA segments. Furthermore, four additional mouse CFSs were found to be homologous to human CFSs on the molecular cytogenetic level (Fra2D-FRA2G, Fra4C2-FRA9E, Fra6A3

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Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 99%

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confidence: 99%

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Common fragile sites are conserved features of human and mouse chromosomes and relate to large active genes

Helmrich

Stout-Weider²,

Hermann³

et al. 2006

Genome Res.

100

101

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“…Fragile sites have been reported in mouse, rat, hamster, cow, cat, and dog (35)(36)(37)(38)(39)(40). They appear to be inherent and universal structures of the mammalian genome.…”

Section: Discussionmentioning

confidence: 99%

Sequence conservation at human and mouse orthologous common fragile regions, FRA3B / FHIT and Fra14A2 / Fhit

Shiraishi

Druck

Mimori

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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It has been suggested that delayed DNA replication underlies fragility at common human fragile sites, but specific sequences responsible for expression of these inducible fragile sites have not been identified. One approach to identify such cis-acting sequences within the large nonexonic regions of fragile sites would be to identify conserved functional elements within orthologous fragile sites by interspecies sequence comparison. This study describes a comparison of orthologous fragile regions, the human FRA3B͞FHIT and the murine Fra14A2͞Fhit locus. We sequenced over 600 kbp of the mouse Fra14A2, covering the region orthologous to the fragile epicenter of FRA3B, and determined the Fhit deletion break points in a mouse kidney cancer cell line (RENCA). The murine Fra14A2 locus, like the human FRA3B, was characterized by a high AT content. Alignment of the two sequences showed that this fragile region was stable in evolution despite its susceptibility to mitotic recombination on inhibition of DNA replication. There were also several unusual highly conserved regions (HCRs). The positions of predicted matrix attachment regions (MARs), possibly related to replication origins, were not conserved. Of known fragile region landmarks, five cancer cell break points, one viral integration site, and one aphidicolin break cluster were located within or near HCRs. Thus, comparison of orthologous fragile regions has identified highly conserved sequences with possible functional roles in maintenance of fragility.C haracterization and sequencing of inherited fragile sites have determined the specific cause of fragility at a number of rare fragile sites; for example, FRA11B is caused by expansion of CGG triplets and FRA16B by AT rich minisatellite repeats (1, 2). These rare fragile sites were isolated by positional cloning of the relevant genomic loci from DNA of family members segregating these rare fragile sites. However, the common non-familial fragile sites (n Ͻ 100) are considered to be normal chromosome structures. To date, common fragile sites FRA3B (3), FRA7H (4), FRA7G (5), and FRA16D (6, 7) have been identified, cloned, and sequenced. Analyses and comparisons of these sequences have not revealed the mechanism of their fragility, although they revealed that common fragile sites are actually large fragile regions (Ϸ150 to 1,000 kbp). Expanded repeats were not found in these fragile regions (4,8,9).The human FRA3B locus at chromosome region 3p14.2 is the most inducible common fragile site, exhibiting apparent breaks in up to 50% of metaphases after exposure to aphidicolin (10). Deletions and structural rearrangements in FRA3B have been observed in a large fraction of tumor types. The tumor suppresser gene FHIT encompasses the FRA3B fragile region and is altered by deletion or translocation in many types of cancer, including those of lung, cervix, esophagus, bladder, and kidney carcinomas (11-16). We have been interested in the mechanism of fragility in this region and its contribution to cancer susceptibility. Previously, w...

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“…Apart from human beings, the FS have been found in other animal species. The gorilla and the chimpanzee are some examples of species evolutionally close to the man, where have been found (Yunis and Soreng 1984, Schmid et al 1985, Smeets and Klundert 1990. The mole rat Nesokia indica (Tewari et al 1987), the Persian vole Ellobius lutescens (Djalali et al 1985), the Chinese hamster (Simi et al 1989) and Drosophyla melanogaster (Laird et a!.…”

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confidence: 99%