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| Status |
Public on Nov 06, 2018 |
| Title |
Integrated network analysis reveals genotype-phenotype correlations in Williams syndrome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Williams Syndrome (WS) is a rare neurodevelopmental disorder caused by heterozygous deletions in a chromosome 7q11.23 region typically encompassing 26-28 genes. WS patients exhibit a wide spectrum of symptoms, including cardiovascular disease, intellectual disability, visuospatial deficits and hypersociability a behavioral profile that contrasts with autism spectrum disorder (ASD). However, the relationship between neuropsychiatric phenotypes and dysregulated gene networks caused by the 7q11.23 deletion is unknown. We report results from a large-scale integrated transcriptome analysis of peripheral blood in clinically evaluated subjects with WS, ASD and matched controls. We identified significantly differential expressed genes in WS as compared with ASD or controls, even after removing genes spanning the 7q11.23 region. Using weighted gene co-expression network analysis (WGCNA), we found that three co-expression modules were upregulated in WS, and were significantly associated with the intermediate phenotypes such as anxiety and attention problems. Notably, these three co-expression modules were only composed of genes located outside of 7q11.23 critical region. One module was associated with immune systems and B cell proliferation. Its top hub gene, BCL11A, is implicated in ASD and chromatin modification. Another module was enriched with genes associated with astrocytes and oligodendrocytes, and the third module was associated with RNA processing and neurons. MicroRNA (miRNA) profiling revealed differentially expressed miRNAs whose targets were enriched in each co-expression module associated with WS. These results identify genes and potential driver miRNAs, located outside of 7q11.23 critical region, that are novel candidates for mediating the neuropsychiatric phenotypes in WS.
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| Overall design |
We profiled gene expression from 32 WS patients, 32 ASD patients and 30 controls using peripheral blood.
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| Contributor(s) |
Kimura R, Hagiwara M |
| Citation(s) |
30362171, 31541176 |
| Submission date |
Nov 07, 2016 |
| Last update date |
Oct 08, 2019 |
| Contact name |
Ryo Kimura |
| E-mail(s) |
kimura.ryo.2w@kyoto-u.ac.jp
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| Organization name |
Kyoto University Graduate School of Medicine
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| Department |
Anatomy and Developmental Biology
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| Street address |
Yoshida-Konoe-cho
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| City |
Kyoto |
| ZIP/Postal code |
606-8501 |
| Country |
Japan |
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| Platforms (1) |
| GPL16699 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Feature Number version) |
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| Samples (94)
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| Relations |
| BioProject |
PRJNA352678 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE89594_RAW.tar |
286.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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