Pluto Biosciences, Inc

GSE64840: Questioned validity of GEDDs in DS

Bulk RNA sequencing

Recently, in studies examining fibroblasts obtained from the tissues of one set of monozygotic twins (i.e. fetuses derived from the same egg) discordant for trisomy 21 (Down syndrome; DS), Letourneau et al. reported the presence of a defined pattern of dysregulation within specific genomic domains they referred to as Gene Expression Dysregulated Domains (GEDDs). GEDDs were described as alternating segments of increased or decreased gene expression affecting all chromosomes. Strikingly, GEDDs in fibroblasts were largely conserved in induced pluripotent cells (iPSCs) generated from the twins fibroblasts as well as in fibroblasts from the Ts65Dn mouse model of DS. Our recent analysis failed to find GEDDs. We reexamined human iPSCs RNAseq data from Letourneau et al., and data from this same research group published earlier examining iPSCs from the same monozygotic twins. In addition, an independent analysis of RNAseq data from Ts65Dn fibroblasts also failed to confirm presence of GEDDs. Our analysis questions the validity of GEDDs in DS. SOURCE: Long,H,Do (lhdo@ucsd.edu) - William Mobley University of California, San Diego, School of Medicine

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