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Patients' Induced Pluripotent Stem Cells (iPSCs) are a desirable disease model for researching tissues that are difficult to access, such as the brain. We and others have demonstrated that trisomy 21 causes genome-wide transcriptional dysregulations using this method. On chromosome 21, the consequences of gene deletion are substantially less well understood. Here, we employ ring chromosome 21 with two deletions spanning 3.8 Mb at the terminal end of 21q22.3, encompassing 60 protein-coding genes, and patient-derived brain cells from a person with neurodevelopmental delay. We developed patientderived iPSCs from fibroblasts that still had the ring chromosome 21 and then converted those iPSCs into neuroepithelial stem cells to examine the molecular effects of the partial monosomy on neural cells. When compared to euploid NESCs, RNA-Seq study of NESCs with the ring chromosome indicated downregulation of 18 genes in the deleted region as well as overall transcriptome dysregulations. We also compared the dysregulated transcriptome profile with that of two NESC lines with trisomy 21, since the deletions on chromosome 21 indicate a genetic "contrary" to the trisomy of the homologous locus. 23 genes on chromosome 21 as well as 149 genes not on chromosome 21 had opposing expression changes, according to the research. Together, these findings shed light on how a partial monosomy of chromosome 21qter during early neuronal differentiation affects both global and chromosome 21-specific gene expression.
