 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Feb 28, 2020 |
| Title |
Comparative and integrated functional genomics analysis of Klinefelter and Turner syndromes reveals network-wide effects of the sex chromosome dosage changes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Other
|
| Summary |
Background: In both Turner syndrome (TS) and Klinefelter syndrome (KS) copy number aberrations of the X chromosome lead to various developmental symptoms. To date there has not been a comprehensive and directly comparative analysis of TS vs. KS regarding the changes on the molecular level
Methods: We analyzed gene expression patterns with RNA-Seq and DNA methylation patterns with the CpGiant assay in lymphocytes, and chromatin conformation with in situ Hi-C in lymphoblastoid cell lines, from TS and KS patients together with their same gender controls.
Results: In TS, differentially expressed escape genes were downregulated but differentially expressed inactive genes were upregulated. In KS, differentially expressed escape genes were upregulated while inactive genes appeared unchanged. Interestingly, 81 differentially expressed genes (DEGs) were associated with both TS and KS, and uniformly displayed expression changes into opposite directions. DEGs on the X chromosome and the autosomes were coexpressed in both TS and KS, indicating that there are molecular ripple effects of the changes in X chromosome dosage that extend to autosomes. Four potentially candidate genes (RPS4X, SEPT6, NKRF and CX0rf57) for KS were identified on Xq. Broad hypomethylation of the X chromosome is observed in TS whereas hypermethylation of chromosome X is present in KS. Only promoters of inactive genes were differentially methylated in both TS and KS while escape genes remained unchanged. The intrachromosomal contact map of the X chromosome in TS was partitioned into two superdomains and exhibited the structure of an active X chromosome.
Conclusions: Components of the molecular basis of TS and KS were identified on the levels of the transcriptome and the epigenome, with candidate central genes on Xp for TS and on Xq for KS. The discovery of shared DEGs indicates the existence of common molecular mechanisms for gene regulation in TS and KS that are transmitting the gene dosage changes to the transcriptome.
|
| |
|
| Overall design |
A direct comparative analysis of TS versus KS and integrative analysis over three levels of genomic and functional genomic activity, in primary lymphocytes from patients and controls for levels of gene expression and levels of DNA methylation and in LCLs for chromosome folding patterns
|
| |
|
| Contributor(s) |
Zhang X, Hong D, Ma S, Ho M, Ward T, Pattni R, Duren Z, Stankov A, Shrestha S, Hallmayer J, Wong W, Reiss A, Urban A |
| Citation(s) |
32071206 |
| Submission date |
Feb 18, 2019 |
| Last update date |
Feb 28, 2020 |
| Contact name |
Xianglong Zhang |
| Organization name |
Amgen Inc.
|
| Department |
Department of Cardiometabolic Disorders
|
| Street address |
One Amgen Center Dr.
|
| City |
Thousand Oaks |
| State/province |
CA |
| ZIP/Postal code |
91320 |
| Country |
USA |
| |
|
| Platforms (3) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (70)
|
|
| Relations |
| BioProject |
PRJNA523024 |
| SRA |
SRP186190 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE126712_RAW.tar |
863.8 Mb |
(http)(custom) |
TAR (of TSV, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...