Genetics: Up and down in Down's syndrome.

Abstract

A comparison of identical human twins, only one of whom has Down's syndrome, reveals a genome-wide flattening of gene-expression levels in the affected individual. See Article p.345 Down's syndrome is thought to be caused by gene expression disturbances, so to understand the molecular mechanisms that underlie the phenotype requires an understanding of the transcriptome differences in cells and tissues carrying the total or partial trisomy of chromosome 21 that is typical of the condition. This study of the transcriptome of fetal cells of monozygotic twins discordant for trisomy 21 shows that differential expression between the twins is organized in domains along all chromosomes. These gene expression dysregulation domains are conserved in the mouse model of Down's syndrome and correlate with the lamina-associated domains and replication domains. Although the overall genome topology is not altered in trisomic cells, the authors report modifications of the chromatin environment influencing the overall transcriptome and suggest that the dysregulation domains they identify may therefore contribute to some Down's syndrome phenotypes.