The Francis Crick Institute
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Gene expression dysregulation domains are not a specific feature of Down syndrome

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journal contribution
posted on 2020-01-03, 12:41 authored by 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
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.


Crick (Grant ID: 10194, Grant title: Tybulewicz FC001194) Crick (Grant ID: 10051, Grant title: Briscoe FC001051) Wellcome Trust (Grant ID: 098328/B/12/Z, Grant title: WT 098328/B/12/Z)