Gene expression meta-analysis reveals the down-regulation of three GABA receptor subunits in the superior temporal gyrus of patients with schizophrenia

2020 ◽  
Vol 220 ◽  
pp. 29-37
Author(s):  
Assaf Frajman ◽  
Nicola Maggio ◽  
Inna Muler ◽  
Vahram Haroutunian ◽  
Pavel Katsel ◽  
...  
Author(s):  
O. V. Varlamova ◽  
A. V. Babkin ◽  
I. S. Berdinskih ◽  
A. K. Nazarov ◽  
A. S. Sadovnikova ◽  
...  

The article presents the results of determining the level of expression of genes encoding GABA receptor subunits GABRA1, GABRB2, and GABRG2 in the hippocampus of rats 24 hours after a single intramuscular administration of the antagonist of the chloro-ion channel of GABA receptor of kloflubicin in a dose of LD25, LD40, LD50, and LD75. It is revealed that kloflubicin has no influence on the relative level of GABRG2 gene expression. At the same time, the relative level of GABRA1 gene expression increases 7,5, 7,0, and 5,0 times after administration of kloflubicin in a dose of LD40, LD50, and LD75, respectively. The relative level of GABRB2 gene expression also increases 3,6 and 2,6 times after administration of kloflubicin in a dose of LD50 and LD75, respectively. It is assumed that increase in the level of gene expression of GABRA1 and GABRB2 in rats after administration of kloflubicin in doses above LD25 is a compensatory reaction of the body to the effect of physiologically active substance, and subunits encoded by these genes α1 and β2, respectively, are included in the mechanism of convulsive effect.


2017 ◽  
Vol 27 (10) ◽  
pp. 1054-1063 ◽  
Author(s):  
Mirko Manchia ◽  
Ignazio S. Piras ◽  
Matthew J. Huentelman ◽  
Federica Pinna ◽  
Clement C. Zai ◽  
...  

2021 ◽  
Vol 22 (14) ◽  
pp. 7624
Author(s):  
Mohammad Saeed ◽  
Alejandro Ibáñez-Costa ◽  
Alejandra María Patiño-Trives ◽  
Laura Muñoz-Barrera ◽  
Eduardo Collantes Estévez ◽  
...  

Objectives: This study employed genetic and functional analyses using OASIS meta-analysis of multiple existing GWAS and gene-expression datasets to identify novel SLE genes. Methods: Four hundred and ten genes were mapped using SNIPPER to 30 SLE GWAS loci and investigated for expression in three SLE GEO-datasets and the Cordoba GSE50395-dataset. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes were used. Confirmatory qPCR on SLE monocytes was performed. The entire 12p11 locus was investigated for genetic association using two additional GWAS. Expression of 150 genes at this locus was assessed. Based on this significance, qPCRs for DNM1L and KRAS were performed. Results: Fifty genes were differentially expressed in at least two SLE GEO-datasets, with all probes directionally aligned. DDX11, an RNA helicase involved in genome stability, was downregulated in both GEO and Cordoba datasets. The most significant SNP, rs3741869 in OASIS locus 12p11.21, containing DDX11, was a cis-eQTL regulating DDX11 expression. DDX11 was found repressed. The entire 12p11 locus showed three association peaks. Gene expression in GEO datasets identified DNM1L and KRAS, besides DDX11. Confirmatory qPCR validated DNM1L as an SLE susceptibility gene. DDX11, DNM1L and KRAS interact with each other and multiple known SLE genes including STAT1/STAT4 and major components of IFN-dependent gene expression, and are responsible for signal transduction of cytokines, hormones, and growth-factors, deregulation of which is involved in SLE-development. Conclusion: A genomic convergence approach with OASIS analysis of multiple GWAS and expression datasets identified DDX11 and DNM1L as novel SLE-genes, the expression of which is altered in monocytes from SLE patients. This study lays the foundation for understanding the pathogenic involvement of DDX11 and DNM1L in SLE by identifying them using a systems-biology approach, while the 12p11 locus harboring these genes was previously missed by four independent GWAS.


2017 ◽  
Vol 8 ◽  
Author(s):  
Sumbul Afroz ◽  
Jeevan Giddaluru ◽  
Sandeep Vishwakarma ◽  
Saima Naz ◽  
Aleem Ahmed Khan ◽  
...  

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