Chromosome spatial clustering inferred from radiogenic aberrations

Abstract

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.

Uncovering Proximity of Chromosome Territories using Classical Algebraic Statistics

“…those aberrations with not all fragments accounted for) and reduces false positives. Following previous publications [2,15] we denote these values by f (j, k) where j and k are the chromosomes that participate in the exchange. These values are presented in Table 1 as a 22 × 22 upper-triangular table.…”

“…To test for proximity of chromosome territories we used a radiation induced exchange type chromosome aberration table published in [2,49]. In these experiments cells from healthy donors were irradiated with sparsely ionizing γ-rays at different doses, and mFISH [46] was used to detect ETCAs.…”

“…ETCAs between two non-homologous chromosomes j and k (j = k) were modeled by a single discrete random variable X with 22 2 = 231 values corresponding to all possible pairs of non-homologue chromosomes with a probability density function given by [2,49]. Each entry f (j, k) holds the number of cells in which at least one exchange between chromosomes j and k was recorded.…”

“…Here we propose a model-based approach that builds a simple log-linear model to test the proximity of pairs of chromosome territories, referred to as chromosome pairs from now on, and we use a Markov Chain Monte Carlo method based on the theory of algebraic statistics to assign significance. The mFISH data we analyze have already appeared in the literature [2,15,34].…”

“…In this type of studies frequency tables were densely populated and with large entries, therefore chi-square statistics were used to find significant clusters of chromosomes. In [2,15] similar tables were generated employing mFISH data. Although more accurate in some respects, the latter data were more sparse and with small entries.…”