Centromeric association of small supernumerary marker chromosomes with their sister-chromosomes detected by three dimensional molecular cytogenetics

Abstract

BackgroundSmall supernumerary marker chromosomes (sSMC) are detected in 0.043% of general population and can be characterized for their chromosomal origin, genetic content and shape by molecular cytogenetic approaches. Even though recently progress was achieved towards genotype-phenotype-correlations of sSMC, nothing is known on the influence that an additional derivative extra chromosome has on the nuclear architecture.ResultsHere we present the first three-dimensional interphase fluorescence in situ hybridization (FISH) studies for the nuclear architecture of sSMC. It could be shown that sSMC derived from chromosomes 15, 16 or 18 preferentially colocalized with one of their corresponding sister chromosomes. This was true in B- and T-lymphocytes as well as in skin fibroblasts. Additionally, a case with a complex sSMC with a karyotype 47,XY,+der(18)t(8;18)(8p23.2 ~ 23.1;18q11.1) was studied. Here the sSMC co-localized with one homologous chromosome 8 instead of 18.ConclusionOverall, there is a kind of "attraction" between an sSMC and one of its homologous sister chromosomes. This seems to be transmitted by the euchromatic part of the sSMC rather than its heterochromatic one.

Small supernumerary marker chromosomes and the nuclear architecture of sperm – a study in a fertile and an infertile brother

“…The latter is in concordance with a previous observation of sSMC positioning in peripheral blood lymphocytes [Klein et al 2012]. However, chromosomes 21 and Y were positioned more centrally in both brothers in comparison to the normal scenario (Figure 2), with both chromosomes being displaced towards the central and/or tail part in the brother I (Figure 3).…”

“…Furthermore chromosome 19 was displaced from the head/middle to the middle/tail region (Figure 3). This data supports the idea that sSMC influences the nuclear architecture [Klein et al 2012]. Also it seems to be obvious that other factors besides sSMC presence can modulate the impact of the latter on the nuclear architecture, as the identical sSMC led to different effects in the two studied cases.…”

“…Also further impact of nuclear architecture on genome function is suggested [Mateos-Langerak et al 2007]. In a previous study we have shown that sSMC-presence has an impact on the nuclear architecture of peripheral blood cells as well as fibroblasts [Klein et al 2012]. Thus, we applied here for the first time 3-dimensional interphase fluorescence in situ hybridization (3D-FISH) for the determination of positioning of sSMC with respect to their sister-and selected other chromosomes in the sperm of two sSMC carriers, brothers with the identical sSMC derived from chromosome 15.…”

To see an interphase chromosome or: How a disease can be associated with specific nuclear genome organization

“…Its application allows the analysis of chromosome (chromosomal loci) positioning in interphase and chromosomal associations at "subchromosomal" resolution in a given nucleus (for more details see [4][5][6][7][8][9]). Evidently, analyzing each chromosomal region is likely to provide more reliable information in contrast to analyzing homogenously painted chromosomes or a single chromosomal region.…”

“…The development of interphase chromosome-specific multicolor banding (ICS-MCB) has led the way towards the high-resolution interphase cytogenetic analysis for Visualization of interphase chromosomes studying chromosomal numbers, structure and spatial arrangement within the nucleus [4][5][6][7]. Using ICS-MCB, chromosome architecture was evaluated in some tissues at "subchromosomal" resolution and specific positioning of chromosomal loci was shown to be linked to generation and behavior of rearranged chromosomes in interphase [8][9][10]. Interestingly, specific chromosome positioning was previously suggested to predispose to cancer-causing chromosomal aberrations [11].…”