Gene expression dysregulation domains are not a specific feature of Down syndrome

• Published in: Nature communications 2019-06, Vol.10 (1), p.2489-2489, Article 2489
• Main Authors: Ahlfors, Helena, Anyanwu, Nneka, Pakanavicius, Edvinas, Dinischiotu, Natalia, Lana-Elola, Eva, Watson-Scales, Sheona, Tosh, Justin, Wiseman, Frances, Briscoe, James, Page, Karen, Fisher, Elizabeth M. C., Tybulewicz, Victor L. J.
• Format: Article
• Language: English
• Subjects: 38; 38/91; 45/91; 631/208/199; 631/208/200; 631/337/100/101; 631/337/572; 64/60; 692/308/1426; Animals; Chromosome 16; Chromosome 21; Chromosomes; Clustering; Disease Models, Animal; Domains; Down syndrome; Down Syndrome - genetics; Down's syndrome; Fibroblasts; Fibroblasts - metabolism; Gene expression; Gene Expression - genetics; Gene Expression Profiling; Genes; Genome; Genomes; Genotype; Genotypes; Hippocampus - metabolism; Humanities and Social Sciences; Mice; multidisciplinary; Multigene Family; Phenotype; Phenotypes; Reproduction (copying); Science; Science (multidisciplinary); Statistical analysis; Transcription; Trisomy; Wildlife conservation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-10129-9

Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), results in a broad range of phenotypes. A recent study reported that DS cells show genome-wide transcriptional changes in which up- or down-regulated genes are clustered in gene expression dysregulation domains (GEDDs). GEDDs were also reported in fibroblasts derived from a DS mouse model duplicated for some Hsa21-orthologous genes, indicating cross-species conservation of this phenomenon. Here we investigate GEDDs using the Dp1Tyb mouse model of DS, which is duplicated for the entire Hsa21-orthologous region of mouse chromosome 16. Our statistical analysis shows that GEDDs are present both in DS cells and in Dp1Tyb mouse fibroblasts and hippocampus. However, we find that GEDDs do not depend on the DS genotype but occur whenever gene expression changes. We conclude that GEDDs are not a specific feature of DS but instead result from the clustering of co-regulated genes, a function of mammalian genome organisation. Gene expression dysregulation domains (GEDDs) have been reported in Down syndrome (DS) cells, where changes in gene expression are clustered. Here the authors find that, while GEDDs are present in DS cells and in the Dp1Tyb mouse model of DS, GEDDs do not depend on the DS genotype and occur whenever gene expression changes, suggesting they result from the clustering of co-regulated genes as a function of mammalian genome organisation.