Gene expression dysregulation domains are not a specific feature of Down syndrome
Helena Ahlfors
Nnneka Anyanwu
Edvinas Pakanavicius
Natalia Dinischiotu
Eva Lana-Elola
Sheona Watson-Scales
Justin Tosh
Frances Wiseman
James Briscoe
Karen Page
Elizabeth MC Fisher
Victor LJ Tybulewicz
10779/crick.11498973.v1
https://crick.figshare.com/articles/journal_contribution/Gene_expression_dysregulation_domains_are_not_a_specific_feature_of_Down_syndrome/11498973
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.
2020-01-03 12:41:25
Animals
Disease Models, Animal
Down Syndrome
Fibroblasts
Gene Expression
Gene Expression Profiling
Genome
Genotype
Hippocampus
Mice
Multigene Family
Phenotype
Tybulewicz FC001194
Briscoe FC001051
AS-ack
BRF