Integrated functional genomic analyses of Klinefelter and Turner syndromes reveal global network effects of altered X chromosome dosage

• DOI: 10.1073/pnas.1910003117
• Publication Date: 2020-02-18T23:15:21Z
• Authors: Xianglong Zhang; David Hong; Shining Ma; Thomas Ward; Marcus Ho; Reenal Pattni; Zhana Duren; Atanas Stankov; Sharon Bade Shrestha; Joachim Hallmayer; Wing Hung Wong; Allan L. Reiss; Alexander E. Urban
• Keywords: Klinefelter syndrome; Gene dosage

In both Turner syndrome (TS) and Klinefelter (KS) copy number aberrations of the X chromosome lead to various developmental symptoms. We report a comparative analysis TS vs. KS regarding differences at genomic network level measured in primary samples by analyzing gene expression, DNA methylation, chromatin conformation. X-chromosome inactivation (XCI) silences transcription from one female mammals, on which most genes are inactive, some escape XCI. TS, almost all differentially expressed down-regulated but inactive up-regulated. KS, up-regulated while majority appear unchanged. Interestingly, 94 (DEGs) overlapped between male comparisons; these uniformly display expression changes into opposite directions. DEGs autosomes coexpressed syndromes, indicating that there molecular ripple effects dosage. Six potential candidate (