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. 2015 Jun;23(2):285-98.
doi: 10.1007/s10577-015-9467-7. Epub 2015 Feb 3.

Expression of the DYRK1A gene correlates with its 3D positioning in the interphase nucleus of Down syndrome cells

Nerea Paz  1 , Izaskun Felipe-Blanco, Félix Royo, Amaia Zabala, Isabel Guerra-Merino, África García-Orad, José L Zugaza, Luis A Parada
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Expression of the DYRK1A gene correlates with its 3D positioning in the interphase nucleus of Down syndrome cells

Nerea Paz et al. Chromosome Res. 2015 Jun.

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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