An iPSC-based model of 47,XYY Jacobs syndrome reveals a DNA methylation-independent transcriptional dysregulation shared with male X aneuploid cells

Autosomal response to Y Chromosome aneuploidy. (A) Venn diagram of shared DEGs comparing 47,XYY versus 46,XY, across three cell types. Log₂FC > |0.58|, FDR < 0.05. (B) GO analysis of 1306 DEGs shared in at least two comparisons. (C) Venn diagram of DEGs in the 47,XYY versus 46,XY contrast and sensitive to Y Chromosome dosage. Dosage–sensitive genes are listed in Supplemental Data S6. FDR < 0.01 and Pearson's correlation value > |0.48|. (BP) Biological process; (CC) cellular component; (MF) molecular function. (D) Gene Ontology analysis on the DEGs responsive to Y Chromosome number showing significantly enriched biological processes. (E) Network analysis plot of genes belonging to enriched biological processes of the GO analysis shown in D. (F) Linear regression analysis of the TMM normalized gene expression in iPSCs carrying zero (46,XX), one (46,XY), or two (47,XYY) Y Chromosomes. The four top hits of autosomal genes with dosage sensitivity to the Y number are shown. Pearson's correlation coefficient (R), P-value, and FDR are indicated.