Premium
Translocation frequencies and chromosomal proximities for selected mouse chromosomes in primary B lymphocytes
Author(s) -
Righolt Christiaan H.,
Wiener Francis,
TaylorKashton Cheryl,
Harizanova Jana,
Vermolen Bart J.,
Garini Yuval,
Young Ian T.,
Mai Sabine
Publication year - 2011
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.21038
Subject(s) - chromosomal translocation , biology , microbiology and biotechnology , chromosome , genetics , gene
Abstract Chromosome positions within the nucleus of mammalian cells are nonrandom and it is assumed that chromosomal neighborhoods affect the probability of translocations. Four chromosomes can be involved in c‐myc ‐activating chromosomal translocations in mouse plasmacytoma (PCT): the c‐myc gene on mouse chromosome 15 can be juxtaposed to either one of the immunoglobulin ( Ig ) loci on chromosomes 12 ( IgH ), 16 ( Ig λ), or 6 ( Ig κ). In the BALB/c mouse, the translocation between chromosomes 12 and 15, T(12;15), is most common (90%) while the other two possible translocations, T(6;15) and T(16;15), are much less common (<10%). In contrast, in the BALB/cRb6.15 mouse, T(6;15) is found with the same frequency as T(12;15). We, therefore, examined the distance between chromosomes 15 and 12, 6, and 16 in primary mouse B lymphocytes in order to examine the effect of the chromosome proximity on the translocation frequency. We performed three‐dimensional fluorescent in situ hybridization (3D‐FISH) with chromosome paints. We acquired three‐dimensional image stacks with 90 slices per stack and used constrained iterative deconvolution. The nucleus and chromosomes were segmented from this image stack and the interchromosomal distances were measured. Chromosomes 6 and 15 were found in close proximity in BALB/cRb6.15 mice (82%), whereas they did not share this neighborhood relationship in BALB/c mice. No other chromosome combinations showed such a high percentage of close proximities in either mouse strain. Chromosome positions contribute to translocation frequencies in mouse PCTs. The BALB/cRb6.15 mouse data argue for a proximity relationship of chromosomes that engage in illegitimate recombination. These positions are not, however, the only contributing factor as the T(12;15) translocation preference in BALB/c mice could not be supported by significantly elevated proximity of chromosomes 12 and 15 versus 12 and 16 or 12 and 6. Moreover, while there is a significant increase in T(6;15) in BALB/cRb6.15 mice, T(12;15) still occurs in this mouse strain. © 2011 International Society for Advancement of Cytometry