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Trisomy 21: How an extra little chromosome throws the entire genome off balance
Date:4/17/2014

ghput sequencing technologies and other biotechnological tools developed within the Department of Genetic Medicine and Development, or in collaboration with scientists in Strasbourg, Barcelona, Amsterdam, and Seattle. They were thus able to eliminate interindividual variations and identify the changes in gene expression exclusively due to trisomy 21.

Small chromosome, big consequences

The researchers noticed that the expression of genes located on all the other chromosomes (outside of chromosome 21) were disturbed in trisomic cells. We were very surprised by this result, explains Audrey Letourneau, who co-authored this study. It does seem that this extra little chromosome has a huge influence on the entire genome.

Generally speaking, chromosomes are divided into domains that contain genes with rather similar levels of RNA production. RNA is the molecule which transmits the information contained in DNA, before this information is translated into proteins with precise functions. In the twin with Down syndrome, the domains are sometimes over-expressed, and sometimes under-expressed when compared with the healthy twin.

By comparing their results with data previously published by other research groups, UNIGE researchers noticed that this specific chromosomes organization correlates with DNA position in the cell nucleus. Therefore, domains over-expressed in the twin with Down syndrome correspond to portions of DNA known to primarily interact with the nucleus periphery.

This study therefore shows for the first time that the DNA position in the nucleus or the biochemical characteristics of DNA-proteins interactions in the trisomic cells is modified, leading to changes in the gene expression profile. Federico Santoni, who co-authored this study, notes that, These changes do not only affect chromosome 21, but the entire genome. The presence of about 1% of extra genetic material in the trisomic cells hence modifies the functi
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Contact: Stylianos Antonarakis
stylianos.antonarakis@unige.ch
41-223-795-708
Universit de Genve
Source:Eurekalert  

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