Chromosomes are predominantly located randomly with respect to each other in interphase human cells

Abstract

To test quantitatively whether there are systematic chromosome–chromosome associations within human interphase nuclei, interchanges between all possible heterologous pairs of chromosomes were measured with 24-color whole-chromosome painting (multiplex FISH), after damage to interphase lymphocytes by sparsely ionizing radiation in vitro. An excess of interchanges for a specific chromosome pair would indicate spatial proximity between the chromosomes comprising that pair. The experimental design was such that quite small deviations from randomness (extra pairwise interchanges within a group of chromosomes) would be detectable. The only statistically significant chromosome cluster was a group of five chromosomes previously observed to be preferentially located near the center of the nucleus. However, quantitatively, the overall deviation from randomness within the whole genome was small. Thus, whereas some chromosome–chromosome associations are clearly present, at the whole-chromosomal level, the predominant overall pattern appears to be spatially random.

Spatial genome organization in the formation of chromosomal translocations

“…The major histocompatibility complex (MHC) class II locus protrudes from the HSA6 chromosome territory when actively transcribing [56,62] and preferentially extends into HSA1, 2 and 9 but not the HSA8 territory [62], indicating preferred neighbors of HSA6 in fibroblasts. The analysis of radiation-induced translocations in human lymphocytes further supports preferred relative positioning of chromosomes [87][88][89][90]. However, some of these studies find a randomness with respect to relative positioning overall, but find a cluster of gene rich chromosomes (HSA1, 16,17,19,22) in the nuclear interior [88,90].…”

“…The analysis of radiation-induced translocations in human lymphocytes further supports preferred relative positioning of chromosomes [87][88][89][90]. However, some of these studies find a randomness with respect to relative positioning overall, but find a cluster of gene rich chromosomes (HSA1, 16,17,19,22) in the nuclear interior [88,90]. Arsuaga et al, [88] found evidence of a cluster of acrocentric, nucleolus-associated, chromosomes, whereas Cornforth et al, [90] did not find a significant level of clustering for these chromosomes.…”

“…However, some of these studies find a randomness with respect to relative positioning overall, but find a cluster of gene rich chromosomes (HSA1, 16,17,19,22) in the nuclear interior [88,90]. Arsuaga et al, [88] found evidence of a cluster of acrocentric, nucleolus-associated, chromosomes, whereas Cornforth et al, [90] did not find a significant level of clustering for these chromosomes. Multicolor imaging experiments on non-irradiated fibroblasts suggest a random positioning of chromosomes with respect to each other, save for 3 pairs of chromosomes (HSA1-2, 2-3 and 13-15) [14].…”

Interphase chromosome folding determines spatial proximity of genes participating in carcinogenic RET/PTC rearrangements

“…It has been suggested that chromosomal loci prone to undergo interchromosomal exchanges may be positioned close to each other due to a nonrandom pairing of the respective chromosome territories (Cremer et al, 1996;Cornforth et al, 2002;Parada et al, 2002). When the genes involved in rearrangements are on the same chromosome, it is reasonable to postulate that structure of the chromatin within a territory determines the positioning of the genes with respect to each other.…”

Parental genomes mix in mule and human cell nuclei

“…A precise antiparallel positioning of chromosome sets was claimed for the mitotic rosette and interphase nuclei, thus advocating a separation of haploid genomes (Nagele et al 1995(Nagele et al , 1998(Nagele et al , 1999. While an antiparallel order could not be confirmed by other groups (Allison and Nestor 1999;Cornforth et al 2002;Bolzer et al 2005;Mayer et al 2005), whether or not parental genomes are separated in another pattern remained unclear.…”