Cartographic study: Breakpoints in 1574 families carrying human reciprocal translocations

Cohen, Olivier; Cans, Christine; Cuillel, Martine; Gilardi, Jean Louis; Roth, H.-R.; Mermet, M.; Jalbert, P; Demongeot, Jacques

doi:10.1007/bf02281879

Cited by 43 publications

(29 citation statements)

References 23 publications

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“…This model postulates that the breakpoints occur mainly within relatively short fragile regions (hot spots of rearrangements). The existence of some fragile regions at the population level was supported by previous studies of cancer and infertility (22,23), but the extent of this phenomenon in molecular evolution became clear only after the human and mouse DNA sequences became available. Although many clinical rearrangement breakpoints form clusters (24,25), there were no previous reports of evolutionary breakpoint clustering, and the relationships between the cytogenetic processes and evolution remain unclear.…”

mentioning

confidence: 49%

Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian evolution

Pevzner

Tesler

2003

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

320

370

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The human and mouse genomic sequences provide evidence for a larger number of rearrangements than previously thought and reveal extensive reuse of breakpoints from the same short fragile regions. Breakpoint clustering in regions implicated in cancer and infertility have been reported in previous studies; we report here on breakpoint clustering in chromosome evolution. This clustering reveals limitations of the widely accepted random breakage theory that has remained unchallenged since the mid-1980s. The genome rearrangement analysis of the human and mouse genomes implies the existence of a large number of very short ''hidden'' synteny blocks that were invisible in the comparative mapping data and ignored in the random breakage model. These blocks are defined by closely located breakpoints and are often hard to detect. Our results suggest a model of chromosome evolution that postulates that mammalian genomes are mosaics of fragile regions with high propensity for rearrangements and solid regions with low propensity for rearrangements.I n a landmark paper, Nadeau and Taylor (1) introduced the notion of conserved segments (i.e., segments with preserved gene orders without disruption by rearrangements) and estimated that there are Ϸ180 conserved segments in human and mouse. In the same paper they provided convincing arguments in favor of the random breakage model of genomic evolution postulated by Ohno (2). The model assumes a random (i.e., uniform and independent) distribution of chromosome rearrangement breakpoints and is supported by the observation that the lengths of synteny blocks shared by human and mouse are well fitted by the predicted distribution imposed by the random breakage model. Since the model was first introduced, it has been analyzed by Nadeau and others (1, 3-6), and it has become widely accepted. It was further supported by studies of significantly larger datasets that confirmed that newly discovered synteny blocks still fit the predicted exponential distribution very well (7-11). These studies, with progressively increasing levels of resolution, made the random breakage model the de facto theory of chromosome evolution.The arguments in favor of the random breakage model usually proceed as follows. One first constructs the distribution of lengths of conserved segments and fits the resulting histogram with the theoretical distribution predicted by the random breakage model. An important implication of this model is that the segment lengths approximate an exponential distribution with density function f(x) ϭ 1͞L e Ϫx/L , where L is the average length of all segments. Nadeau and Taylor (1) did not have information about all segments because most of them were still undiscovered in 1984. However, they were able to estimate L (and therefore the number of still undiscovered segments) from the small set of already discovered segments. The relatively small departure from an exponential distribution was attributed to missing information about some conserved segments. Of course, there was always a danger t...

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mentioning

confidence: 49%

Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian evolution

Pevzner

Tesler

2003

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

320

370

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“…Pericentric inversion inv(9)(p11q13) is one of the most common chromosome heteromorphisms with a frequency of B1% in the general population, 18 and chromosome 9 is frequently involved in reciprocal translocations in humans. 19 Furthermore, this chromosome is more represented in unrejoined breakage events than expected by chance in human sperm complements. 20,21 To our knowledge, no FISH studies regarding the effect of age on structural aberrations of chromosome 9 in sperm have been performed, and only one recent sperm study 13 has been carried out to determine the incidence of numerical aberrations for chromosome 9 in relation to age using this technique.…”

Section: Introductionmentioning

confidence: 98%

Linear increase of structural and numerical chromosome 9 abnormalities in human sperm regarding age

et al. 2003

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A simultaneous four-colour fluorescence in situ hybridisation (FISH) assay was used in human sperm in order to search for a paternal age effect on: (1) the incidence of structural aberrations and aneuploidy of chromosome 9, and (2) the sex ratio in both normal spermatozoa and spermatozoa with a numerical or structural abnormality of chromosome 9. The sperm samples were collected from 18 healthy donors, aged 24 -74 years (mean 48.8 years old). Specific probes for the subtelomeric 9q region (9qter), centromeric regions of chromosomes 6 and 9, and the satellite III region of the Y chromosome were used for FISH analysis. A total of 190 117 sperms were evaluated with a minimum of 10 000 sperm scored from each donor. A significant linear increase in the overall level of duplications and deletions for the centromeric and subtelomeric regions of chromosome 9 (Pr0.002), chromosome 9 disomy (Po0.0001) as well as diploidy (Po0.0001) was detected in relation to age. The percentage of increase for each 10-year period was 29% for chromosome 9 disomy, 18.8% for diploidy, and ranged from 14.6 to 28% for structural aberrations. Our results indicate a linear increase in structural aberrations and disomy for chromosome 9 in sperm with respect to age.

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“…Intrachromosomal telomeric-like sequences studies: Azzalin et al (1997), Ruiz-Herrera et al (2002b) and Ruiz-Herrera et al (2004). Clinical cytogenetic studies: Kaiser (1984), Fryns et al (1986), A French collaborative study (1986), Kleezkowska et al (1987), Madan (1995), Cohen et al (1996) and Mitelman et al (1997).…”

Section: Methodsmentioning

confidence: 99%

“…Human evolutionary chromosome bands which are boundaries for ancestral chromosome segments (see Fig. 1) in different species from different orders (Smeets and Van de Klunder, 1990); red stars: human chromosome bands significantly affected by X irradiation (Barrios et al, 1989); green stars: M. fascicularis chromosome bands significantly affected by X irradiation located in the homologous human chromosome band (Borrell et al, 1998a, b); i: evolutionary inversions; f: evolutionary fusion/fission events; b: breakpoints detected in human pathologies (Kaiser, 1984;Fryns et al, 1986;A French collaborative study, 1986;Kleezkowska et al, 1987;Madan, 1995;Cohen et al, 1996;Mitelman et al, 1997).…”

Section: Human Evolutionary Chromosome Bands That Are Boundaries For mentioning

confidence: 99%

Evolutionary conserved chromosomal segments in the human karyotype are bounded by unstable chromosome bands

Ruiz‐Herrera¹,

García

Mora

et al. 2004

Cytogenet Genome Res

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In this paper an ancestral karyotype for primates, defining for the first time the ancestral chromosome morphology and the banding patterns, is proposed, and the ancestral syntenic chromosomal segments are identified in the human karyotype. The chromosomal bands that are boundaries of ancestral segments are identified. We have analyzed from data published in the literature 35 different primate species from 19 genera, using the order Scandentia, as well as other published mammalian species as out-groups, and propose an ancestral chromosome number of 2n = 54 for primates, which includes the following chromosomal forms: 1(a+c₁), 1(b+c₂), 2a, 2b, 3/21, 4, 5, 6, 7a, 7b, 8, 9, 10a, 10b, 11, 12a/22a, 12b/22b, 13, 14/15, 16a, 16b, 17, 18, 19a, 19b, 20 and X and Y. From this analysis, we have been able to point out the human chromosome bands more “prone” to breakage during the evolutionary pathways and/or pathology processes. We have observed that 89.09% of the human chromosome bands, which are boundaries for ancestral chromosome segments, contain common fragile sites and/or intrachromosomal telomeric-like sequences. A more in depth analysis of twelve different human chromosomes has allowed us to determine that 62.16% of the chromosomal bands implicated in inversions and 100% involved in fusions/fissions correspond to fragile sites, intrachromosomal telomeric-like sequences and/or bands significantly affected by X irradiation. In addition, 73% of the bands affected in pathological processes are co-localized in bands where fragile sites, intrachromosomal telomeric-like sequences, bands significantly affected by X irradiation and/or evolutionary chromosomal bands have been described. Our data also support the hypothesis that chromosomal breakages detected in pathological processes are not randomly distributed along the chromosomes, but rather concentrate in those important evolutionary chromosome bands which correspond to fragile sites and/or intrachromosomal telomeric-like sequences.

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Cartographic study: Breakpoints in 1574 families carrying human reciprocal translocations

Cited by 43 publications

References 23 publications

Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian evolution

Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian evolution

Linear increase of structural and numerical chromosome 9 abnormalities in human sperm regarding age

Evolutionary conserved chromosomal segments in the human karyotype are bounded by unstable chromosome bands

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