CRG:  Trisomy 21: how an extra little chromosome throws the entire genome off balance

CRG: Trisomy 21: how an extra little chromosome throws the entire genome off balance

News from the CRG

Despite much research, the exact mechanisms causing the various symptoms associated with Down syndrome remain a mystery. According to a hypothesis called "gene dosage disequilibrium", the presence of a third chromosome 21 could influence the expression of all the other genes in the genome. That is, this extra genetic material could disrupt the process through which information carried in the genes is decoded, therefore modifying the cellular function.

At the University of Geneva, Stylianos Antonarakis's team has the unique opportunity to examine the genomes of two identical twins with the exact same genetic makeup, except for an extra chromosome 21 present in one of them. Indeed, the chromosome 21 distribution error can take place during an early cellular division, after the original fertilized egg splits in two.

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.'

This study opens the door to a new way of understanding the molecular mechanisms that explain the symptoms of Down syndrome. The vast amount of genomic data obtained with high-through output sequencing techniques offer lots of possibilities for researchers. "This advancement has been possible thanks to the extraordinary development in genomic technologies, that allow us to interrogate the activity of the genome with unprecedented resolution" says Roderic Guigó, coauthor, head of the Computational Biology of RNA Processing group at the CRG and professor at the Universitat Pompeu Fabra (UPF).

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Letourneau, A., et. al. "Domains of genome-wide gene expression dysregulation in Down’s syndrome. Nature Magazine, April 2014. doi:10.1038/nature13200