Abstract
Down syndrome is a common birth defect caused by trisomy of chromosome 21. Chromosomes occupy distinct territories in interphase nuclei, and their distribution within the nuclear space is nonrandom. In humans with Down syndrome, two chromosomes 21 frequently localize proximal to one another and distant from the third chromosome. Here, we investigated the nuclear organization of DYRK1A and SOD1, two genes mapping to chromosome 21 that greatly contribute to the pathology. We found that DYRK1A conserves its central positioning between normal and trisomic cells, whereas SOD1 adopts more peripheral distribution in trisomic cells. We also found that the relative position of these genes with respect to each other varies among the different copies of chromosome territories 21 within a cell, and that this distinct distribution is associated with differences in their expression levels. All together, our results may explain, at least in part, the difference in the expression level of these two genes implicated in the pathogenesis of Down syndrome.
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Abbreviations
- CT:
-
Chromosome territories
- DAPI:
-
4’,6-Diamidino-2-phenylindole
- DNA:
-
Deoxyribonucleic acid
- DS:
-
Down syndrome
- DSCR:
-
Down syndrome critical region
- FISH:
-
Fluorescence in situ hybridization
- Immuno-FISH:
-
Indirect immunofluorescence combined with FISH
- NOR:
-
Nucleolar organizing region
- PCR:
-
Polymerase chain reaction
- PBS:
-
Phosphate-buffered saline
- SSC:
-
Saline-sodium citrate
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Acknowledgments
We would like to thank Dr Karen Meaburn and Dr Sylvia Ritter for critical reading of the manuscript. This work was supported by funding from National Council of Sciences and Technologies (CONICET); Argentine Agency for Science and Technology (ANPCyT – FONCyT: PICT-2011-1897). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Paz, N., Felipe-Blanco, I., Royo, F. et al. Expression of the DYRK1A gene correlates with its 3D positioning in the interphase nucleus of Down syndrome cells. Chromosome Res 23, 285–298 (2015). https://doi.org/10.1007/s10577-015-9467-7
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DOI: https://doi.org/10.1007/s10577-015-9467-7