Researchers have been interested in proteins synthesized from genes in cells to better understand trisomy 21. The deregulation of the secretion of these proteins in all cells could explain the disorders.
Research on trisomy 21, the most common genetic disease, is progressing. Researchers at the University of Geneva have achieved a world first by showing the responsibility for the uncontrolled deregulation of proteins inside all cells of the body in Down syndrome. The results of their research were published in the journal Nature Communications.
Their work reveals that trisomy 21 affects all the proteins encoded from other chromosomes and not just those of the extra chromosome 21 in this disease. Cell function is overwhelmed by excess protein synthesized from triplicate genes and they cannot regulate it.
A remarkable advance
To conduct their research, scientists had to overcome significant technical difficulties. Two teams worked together, one from the University of Geneva, and another from ETH Zurich.
Together, they succeeded in quantifying 4000 of the 10,000 proteins that are normally synthesized by skin cells. To better understand the differences between a person with Down’s syndrome and a person who does not, the researchers compared the genetic backgrounds of two twins, one of whom has Down’s syndrome.
An overdose of protein in cells
They realized that trisomy 21 causes an “overdose of messenger RNAs and proteins” inside all the cells of the body, which results in the disruption of the functioning of all cells. This explains why trisomy 21 has such extensive consequences (changes in morphology and intellectual functioning, poor muscle tone and congenital heart abnormalities), while chromosome 21 is very small and encodes few proteins.
Dysregulation and lack of cellular energy
But they also observed that, in the case of a person with Down’s syndrome, the cellular mechanism that regulates protein production is malfunctioning. In addition, people with Down’s syndrome are also affected by a lower presence of proteins that are used to build the mitochondria, the powerhouses of the cell. The functioning of all cells is therefore affected.
Now, researchers want to understand the precise roles of each of these cellular proteins, to better understand their link with each of the symptoms of Down’s syndrome.
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