Computer analysis of mFISH chromosome aberration data uncovers an excess of very complicated metaphases

Vázquez, Mariel; Greulich-Bode, Karin M.; Arsuaga, Javier; Cornforth, Michael N.; Brückner, Martina K.; Sachs, Rainer K.; Hlatky, Lynn; Molls, M.; Hahnfeldt, Philip

doi:10.1080/09553000210166354

Cited by 18 publications

(7 citation statements)

References 64 publications

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“…The model of Carrano and Heddle (1973) as implemented by Braselmann et al (1986) was incorporated into CAS by Vazquez et al (2002). Six adjustable parameters are needed to model cell proliferation and selection.…”

Section: Mathematical Methods To Model Lymphocyte Proliferationmentioning

confidence: 99%

Chromosome spatial clustering inferred from radiogenic aberrations

Arsuaga¹,

Greulich-Bode

Vázquez

et al. 2004

International Journal of Radiation Biology

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Abstract.Purpose: Analysing chromosome aberrations induced by low linear energy transfer (LET) radiation in order to characterize systematic spatial clustering among the 22 human autosomes in human lymphocytes and to compare their relative participation in interchanges. Materials and methods: A multicolour fluorescence in situ hybridization (mFISH) data set, specifying colour junctions in metaphases of human peripheral blood lymphocytes 72 h after in vitro exposure to low LET radiation, was analysed separately and in combination with previously published results. Monte Carlo computer simulations and mathematical modelling guided data analysis. Results and conclusions: Statistical tests on aberration data confirmed two clusters of chromosomes, {1, 16, 17, 19, 22} and {13, 14, 15, 21, 22}, as having their members being on average closer to each other than randomness would predict. The first set has been reported previously to be near the centre of the interphase nucleus and to be formed mainly by gene-rich chromosomes, while the second set comprises the nucleolus chromosomes. The results suggest a possible interplay between chromosome positioning and transcription. A number of other clusters suggested in the literature were not confirmed and considerable randomness of chromosome-chromosome juxtapositions was present. In addition, and consistent with previous results, it was found that chromosome participation in interchanges is approximately proportional to the two-thirds power of the DNA content.

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Section: Mathematical Methods To Model Lymphocyte Proliferationmentioning

confidence: 99%

Chromosome spatial clustering inferred from radiogenic aberrations

Arsuaga¹,

Greulich-Bode

Vázquez

et al. 2004

International Journal of Radiation Biology

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“…Also, in radiation biology, chromosome aberrations for k . 2 (indicative of chromosome damage rather than evolutionary viable variations) may be more common (e.g., complex rearrangements in irradiated human lymphocytes [23][24][25][26]). Thus, both the existing controversy about RBM and radiation/cancer biology call for studies of k-break rearrangements for k .…”

Section: Introductionmentioning

confidence: 99%

Are There Rearrangement Hotspots in the Human Genome?

Alekseyev

Pevzner

2005

PLoS Comput Biol

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In a landmark paper, Nadeau and Taylor [18] formulated the random breakage model (RBM) of chromosome evolution that postulates that there are no rearrangement hotspots in the human genome. In the next two decades, numerous studies with progressively increasing levels of resolution made RBM the de facto theory of chromosome evolution. Despite the fact that RBM had prophetic prediction power, it was recently refuted by Pevzner and Tesler [4], who introduced the fragile breakage model (FBM), postulating that the human genome is a mosaic of solid regions (with low propensity for rearrangements) and fragile regions (rearrangement hotspots). However, the rebuttal of RBM caused a controversy and led to a split among researchers studying genome evolution. In particular, it remains unclear whether some complex rearrangements (e.g., transpositions) can create an appearance of rearrangement hotspots. We contribute to the ongoing debate by analyzing multi-break rearrangements that break a genome into multiple fragments and further glue them together in a new order. In particular, we demonstrate that (1) even if transpositions were a dominant force in mammalian evolution, the arguments in favor of FBM still stand, and (2) the ''gene deletion'' argument against FBM is flawed.

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“…Current views on mechanisms of radiation induced chromosomal exchange aberration (CA) formation suggest misrepair of chromosomal lesions located in spatial proximity to each other [e.g. Vazquez et al 2002, Zhang et al 2010, Eidelman and Andreev 2015. Since the induction of CA requires the contacts of damaged chromosomal loci, immediate (contact-first mechanism) and delayed (breakage-fist mechanism), CAs should depend of chromosomal contact pattern.…”

Section: Introductionmentioning

confidence: 99%

Relationships between chromosomal aberration breakpoints and chromosomal contacts: biophysical modeling study

et al. 2016

Preprint

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Radiation-induced chromosomal exchange aberrations (CAs) are formed presumably at contacts of damaged chromosomal loci. For sparsely ionizing radiation, distribution of aberrations along the chromosome should depend on distribution of contacts, i.e. on 3D organization of the chromosome. The progress in experimental techniques for study of chromosomal contacts and for precise localization of aberration breakpoints allows to verify contacts-based mechanisms of CA formation experimentally. In the present work, the polymer model of mouse interphase chromosome 18 is developed. On this basis the experimental data on contacts and aberrations are jointly analyzed. We demonstrate high correlation between chromosomal contacts and aberrations breakpoint distributions. Possible factors and alternative mechanisms which could modify breakpoint distributions are discussed.

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Computer analysis of mFISH chromosome aberration data uncovers an excess of very complicated metaphases

Cited by 18 publications

References 64 publications

Chromosome spatial clustering inferred from radiogenic aberrations

Chromosome spatial clustering inferred from radiogenic aberrations

Are There Rearrangement Hotspots in the Human Genome?

Relationships between chromosomal aberration breakpoints and chromosomal contacts: biophysical modeling study

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