GABRA1

..Transcriptional activity of this promoter construct was strongly repressed by chronic administration of lorazepam...

..the possibility that the gene for the gamma-aminobutyric acid type A (GABAA) receptor alpha-1 subunit (GABRA1) might be associated with depressive symptomatology in a sample of mood disorder subjects...

..In addition, the regulation of GABAAR-alpha1 expression by c-myc provides a potential direct role for the Myc proteins in neurological processes and neurodegenerative disorders...

..We investigated the expression of four GABA(A) receptor subunits and observed significant reductions in GABRA1, GABRA2, GABRA3, and GABRB3 in parietal cortex (Brodmann's Area 40 (BA40)), while GABRA1 and GABRB3 were ..

..The GABRA1 gene encodes one of the subunits of GABA-A receptor and is located on human chromosome 5q34-q35, which is a region ..

..receptor D2 (DRD2), D4 exon 3 (DRD4), and gamma-aminobutyric acid type A (GABA(A)) receptor alpha-1 subunit (GABRA1) gene variants on the efficacy of lithium prophylaxis in mood disorders...

..The cloned human GABAA receptor subunits induce the formation of GABA-gated chloride channels when expressed in mammalian cells...

..GABA also acts through GABA(A) receptors containing the alpha(1) subunit on specific striatal GABAergic interneurons and on output neurons of the globus pallidus and substantia nigra pars reticulata...

..The present models might be also useful in understanding the basic mechanism of operation of the GABA-A receptors, stimulating novel strategies for developing more specific drugs and better treatments...

Mutations in inhibitory GABAA receptor subunit genes (GABRA1, GABRB3, GABRG2 and GABRD) have been associated with genetic epilepsy syndromes including childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME), pure febrile ..

..were screened in the following genes: GABRG1, GABRA2, GABRA4, and GABRB1 on chromosome 4p12; GABRB2, GABRA6, GABRA1, GABRG2, and GABRP on 5q34-q35.1; GABRR1 and GABRR2 on 6q15; and GABRA5, GABRB3, and GABRG3 on 15q12...

..For the genetic study of complex diseases, association analysis has been recommended because of its higher power than that of the linkage analysis for detecting genes with modest effects on disease...

..the predicted order of the 12 loci is cen-ADRB2-PDEA-CSF1R-RPS14-ANX6-SPARC++ +-GLRA1-GLUR1-ADRA1B-IL12- GABRG2-GABRA1-tel...

..Myoclonic epilepsy is a common epileptic syndrome with high genetic contribution. We described a pedigree in which 10 individuals presented with a non-progressive, adult-onset myoclonic epilepsy...

..abundant gamma-amino-n-butyric acid type A receptor subtype in mammalian brains and the corresponding genes, the GABRA1, GABRB2, and GABRG2 genes, are located in chromosomal region 5q34 that several genome wide scans have implicated ..

..possible explanation for the anxiolytic-like effect of the deletion of the Lsamp gene is a shift in balance in the Gabra1 and Gabra2 genes in the temporal lobe in favor of the Gabra2 transcript, encoding α2 subunit of GABA(A) receptors ..

..of allelic expression in heterozygotes of SNP rs2229944 (C/T) in GABRB2 or rs2290732 (G/A) in the neighboring GABRA1 was compatible with imprinting effects on gene expression...

..Expression of glutamate decarboxylase 1 (GAD1), GABA-A receptor subunit alpha-1 (GABRA1), and potassium channel subfamily K member 15 (KCNK15) was decreased ipsilaterally in the cochlear nucleus and ..

..Among recently reported candidate genes, BDNF, G72, AKT1, GRIN2A, XBP1, GRK3, HTR4, IMPA2 and GABRA1 may have some importance...

..dominant transmission have revealed 11 genes (KCNQ2, KCNQ3, CHRNA4, CHRNA2, CHRNB2, SCN1B, SCN1A, SCN2A, GABRG2, GABRA1, and LGI1) and numerous loci for febrile seizures and epilepsies...

..protein, we compared the protein-level expression and localization of gephyrin and the GABA(A) receptor alpha1 (GABRA1) and gamma2 (GABRG2) subunits...

..For the Rhenish German and Schleswig draft horses, additional QTL on ECA4 and 10 and for the South German draft horses an additional QTL on ECA7 were found...

..mutations and susceptibility alleles determined in the genes that code for the subunits of GABA receptors (GABRG2, GABRA1, GABRB3, GABRA5, GABA(B1) and GABA(B2)), calcium channels (CACNA1A, CACNA1G, CACNA1H, CACNA1I, CACNAB4, CACNAG2 ..

..The aim of our study was to find out the possible role of single nucleotide polymorphisms (SNPs) present in GABRA1 IVS11+15 A>G (rs2279020) and GABRG2 588C>T (rs211037) genes in seizure susceptibility and pharmaco-resistance in ..

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..We conclude that these genes are not a major genetic factor in familial TLE preceded by FS...

..was used to investigate the topographic distribution of the alpha1 subunit of the GABA receptor (GABRA1) in guinea pig inferior colliculus after treatments that caused a unilateral loss of peripheral neural sensitivity ..

..in SCN1A, SCN2A, SCN1B, and GABRG2, autosomal-dominant juvenile myoclonic epilepsy (JME) due to a mutation in GABRA1 and mutations in CLCN2 associated with several IGE sub-types...

..Because both agents have been reported to induce depletion of B cells, we sought to investigate their cytotoxic activity on myeloma cells...

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..In the present study, analysis of cortical GABA(A) subunit expression was performed in control human tissue obtained from infancy through adolescence, and was compared to that from similarly aged children with intractable focal epilepsy...

..0253). These results confirmed our earlier findings, indicating GABRA4 and GABRB1 as genes contributing to autism susceptibility, extending the effect to multiple ethnic groups and suggesting seizures as a stratifying phenotype...

..Mutations in the alpha-1 subunit of the GABAA receptor (GABRA1) and EFHC1 genes have been reported in a few families with autosomal dominant (AD) JME...

..dominant mutation associated with childhood absence epilepsy that generates a PTC in exon 8 of the 9 exon GABRA1 gene that is 74 bp upstream of intron 8...

..dominant transmission have revealed 11 genes (KCNQ2, KCNQ3, CHRNA4, CHRNA2, CHRNB2, SCN1B, SCN1A, SCN2A, GABRG2, GABRA1, and LGI1) and numerous loci for febrile seizures and epilepsies...

..Experimentally naïve Wfs1-deficient animals displayed a significant down-regulation of alpha1 (Gabra1) and alpha2 (Gabra2) subunits of GABA(A) receptors in the temporal lobe and frontal cortex...

..Sensitivity to Zn2+ was restored in the double mutant receptor, alpha1beta2gamma2 (I282H; K285E), in which the competition with lysine was removed and a more favorable Zn2+ binding site was formed...

..It is also associated with a variety of neurological diseases. Changes in GABA(A) receptor alpha1 subunit gene (GABRA1) expression have been reported in animal models of epilepsy, alcohol abuse, withdrawal, and stress...

..been proposed to modulate the pathophysiology of the disease which is represented by the involvement of genes like GABRA1, GABRP, GABRA6 and Reelin...

A gene cluster consisting of the four gamma-aminobutyric acidA (GABAA) receptor subunit genes GABRA1, GABRA6, GABRAB2, and GABRG2 was assigned to a yeast artificial chromosome (YAC) contig of 5q33...

..In this study, we tested the hypothesis that mutations in the GABRA1, GABRB3, and GABRG2 genes encoding the alpha1, beta3, and gamma subunits of the GABA(A) receptor are involved in ..

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..Topping the list of candidate genes, we have three genes involved in GABA neurotransmission (GABRA1, GABBR1, and GAD2), one gene involved in glutamate neurotransmission (GRIA2), one gene involved in neuropeptide ..

..genes encode for some important central nervous system ion channels (KCNJ10, KCNJ3, KCNQ2/KCNQ3, CLCN2, GABRG2, GABRA1, SCN1B, and SCN1A), while many others encode for ubiquitary enzymes that play crucial roles in various metabolic ..

..In the occipital and cerebellar cortex, we did not see disease-specific differences of the mRNA expression of the investigated subunits...

..Our method of phenotype refinement may be useful in studies of other complex psychiatric and non-psychiatric disorders...

..These findings demonstrated that, in addition to causing a heterozygous loss of function of alpha1(AD) subunits, this epilepsy mutation also elicited a modest dominant negative effect that likely shapes the epilepsy phenotype...

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..Finally, it was demonstrated that the sequences investigated cause a selective assembly with certain subunits only and thus influence subunit arrangement within GABA(A) receptors...

..These results suggest that PKC-dependent phosphorylation of the α4 subunit plays a significant role in enhancing the cell surface stability and activity of GABA(A)R subtypes that mediate tonic inhibition...

..The GABAergic system clearly emerges as an attractive target for therapy of the fragile X syndrome, and thus provides an excellent example of how genetic research can lead to unique opportunities for treatment...

..These results suggest that PKCgamma may be involved in GABA(A) receptor adaptations following chronic ethanol consumption...

..We report that an Ala322Asp mutation in GABRA1, encoding the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A (GABA(A)), is found in affected ..

..The MDR method indicated that a combination of four SNPs (rs12658835 and rs35166395 from GABRA1, rs2228622 from EAAT3 and rs2304725 from GAT3) was the best model for predicting susceptibility to AED resistance ..

..into 25 linkage groups, 22 of which could be assigned physically to 18 different chromosomes (ECA1, ECA2, ECA3, ECA4, ECA5, ECA6, ECA7, ECA9, ECA10, ECA11, ECA13, ECA15, ECA16, ECA18, ECA19, ECA21, ECA22, and ECA30)...

..of additional mutations in the GABA(A) receptor by direct sequencing of the complete open reading frame of the GABRA1 and GABRG2 genes from a cohort of French Canadian families with idiopathic generalized epilepsy (IGE)...

..Finally, some compounds were submitted to molecular docking calculations along with molecular dynamics simulations in the Cromer's GABA(A) homology model...

..87 at a theta of 0.069 (males) and 0.100 (females). These results reveal the clustering of GABRA6, GABRA1, and the GABAA receptor gamma 2-subunit gene (GABRG2) on distal chromosome 5q.

..encoding growth factors, growth factor receptors, or hormone receptors (IL3, IL4, IL5, CSF1R, FGFA, ADRB2, GRL, GABRA1, and DRD1) as well as four other loci (FER, SPARC, RPS14, and CD14) to generate a radiation hybrid map of the area ..

..RH mapping eliminated the candidate genes GABRA1 and GABRG2, which encode GABA-A receptor components, by showing that they are telomeric to the target region.

..Thus, an activity-dependent physical and functional interaction between CaN and GABA(A) receptors is both necessary and sufficient for inducing LTD at CA1 individual inhibitory synapses...

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..polymorphisms that are reported here for the first time include AGTRL2, CAT, CHRNA5, CTSG, CYP2D6, DLD, ERCC1, GABRA1, GABRP, HNRPH3, HIP1, IGKV1-9, KCNJ15, KCNK6, KLK1, MSMB, MYOC, NPY2R, NOTCH4, ORM2, PEDF, PTPRCAP, ST16 (IL24), ..

..Here we provide suggestive evidence implicating a sixth member of the gene family, GABRR1 (gene-wide P = 0.0058; experiment-wide corrected significance P = 0.052)...

..Single nucleotide polymorphisms (SNPs) of the GABAA receptor subunits GABRB2, GABRA6, GABRA1, and GABRG2 were examined in 178 male Han Chinese heroin-dependent and 170 male control subjects...

..aimed to validate fluorescent in situ hybridization (FISH) probes to label specific equine chromosomes (ECA2 and ECA4) in interphase nuclei and thereby determine whether numerical chromosome abnormalities occur in horse embryos ..

..047), GABAA-beta2 1412C/C (P = .01), or EAAT2 603G/A (P = .022) genotypes. Combined DRD2TaqI A or B with GABAA-beta2 or EAAT2 G603A genotypes may have a concerted influence in the predisposition to alcoholism...

..levels of a number of GABAA subunits previously shown to be important components of fear processing (Gabra3, Gabra1 and Gabrg2) were also altered...

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..We show that the alpha1 and alpha6 subunits immobilize recombinant GABAAR in transfected cells. This is consistent with the immobility of native receptors in CG cells, which express alpha1 and alpha6...

..This model also correctly predicts the actions of etomidate on GABA(A) receptors containing a point mutation that increases constitutive gating activity...

..Therefore, production of the mutated subunit could cause global hyperexcitability throughout the brain, leading to generalized seizures with juvenile onset...

An Ala322Asp mutation in the GABRA1 gene was recently reported to be responsible for causing the autosomal dominant (AD) form of juvenile myoclonic epilepsy (JME) in a French-Canadian family...

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..Previous studies suggest that pre/probiotics can be used in the prevention and treatment of early allergic disease in newborns and young children...

..cohort of subjects to evaluate the gene for the gamma-aminobutyric acid type A (GABA(A)) receptor alpha-1 subunit (GABRA1)...

..We report here a highly polymorphic (dC-dA)n repeat within the human alpha 1-subunit gene (GABRA1)...

..Three genes (COMT, DRD4, and GABRA1) were associated with METH abuse, nine (ARRB2, BDNF, CYP2D6, GLYT1, GSTM1, GSTP1, PDYN, PICK1, and SLC22A3) with ..

..protein (CREB) family member ICER (inducible cAMP early repressor) to bind with phosphorylated CREB at the Gabra1:CRE site...

..05) extended haplotypes showed an association with AUD that was determined by GABRA2. Our results suggest that there are likely to be independent, complex contributions from both GABRG1 and GABRA2 to alcoholism vulnerability...

..mutation in a multigeneration JME family has been recently found in the alpha1-subunit of the GABAA receptor (GABRA1), predicting the single amino acid substitution A322D...

..Recovery in the paired pulse experiments was faster in HEK293 cells. In conclusion, we provide evidence that recombinant receptors may show functional differences when expressed in different cells...

..Our study provides preliminary evidence that the GABA(A) subunit genes on 5q33 may preferentially contribute to methamphetamine use disorder in females...

..During gating, Asp 149 and Lys 279 seem to move closer to one another, providing a potential mechanism for the coupling of ligand binding to opening of the ion channel...

..These data are consistent with a role for these residues at the extracellular end of TM4 in anesthetic modulation of GABA(A) receptors...

..In addition to predicting the most likely inter-subunit arrangement, the model predicts which residues form the GABA and benzodiazepine binding sites...

..0015). These differences, however, were not significant after Bonferroni correction. These data did not support our hypothesis that polymorphisms of the GABA(B) receptor gene may confer vulnerability for schizophrenia...

..This subunit has a unique distribution, with studies so far suggesting significant expression within monoaminergic neurons of both human and monkey brain...

..We propose that protein phosphorylation at a tyrosine kinase-dependent site, and a distinct unidentified site, which is dephosphorylated by calcineurin, maintains the function of GABAA receptors...

..These data indicate that gamma 3-subunits can combine with most alpha-subunits to form a multiplicity of GABAA receptors with distinct pharmacology...

..gene association approach to investigate a group of gamma-aminobutyric acid (GABA) A receptor subunit genes (GABRA1, GABRA6, GABRB2, GABRG2, and GABRP) within our linkage peak...

..These data are consistent with the prediction that the mutated residue pairs are located close to each other...

..We thus conclude that C-terminal motifs are also important determinants of Cys-loop receptor assembly...

..Epigenetic mechanisms may be involved in the reprogramming of gene expression in response to stressful stimuli. This investigation determined whether epigenetic phenomena might similarly be associated with suicide/depression...

..These results suggest that the mutant subunit can form functional receptors, but that these have a shorter lifetime on the plasma membrane...

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..A-->G) in position 10 in the intron 3 (rs949626) of the EFHC1 gene; and a polymorphism (T-->C) of the exon of the GABRA1 gene, without aminoacidic exchange...

..We performed mutation analysis of all the coding exons of GABA(A) receptor alpha1, beta2 and gamma2 subunit (GABRA1, GABRB2 and GABRG2) genes by direct sequencing to clarify whether there was common molecular biological mechanism ..

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..expression play a critical role in the process of epileptogenesis by re- establishing normal levels of GABRA4 and GABRA1 following pilocarpine-induced SE and determining whether development of spontaneous seizures is subsequently ..

..JME has been shown to be genetically linked to the HLA region of chromosome 6. This JME locus has been designated EJM-1...

..identified long-term changes in GABAR a subunit gene expression, including decreases in expression of the a1 gene (Gabra1) in rat hippocampal dentate granule neurons following status epilepticus (SE) that are associated with later ..

..The DNA from the 782 adults will be used to conduct candidate gene analyses for GABRA2, GABRA1, CHRM2, CRHR1, CNR1, 5HTTLPR, and DRD2 for alcohol and depression phenotypes...

..Building a more complete 3-dimensional model of an anesthetic binding site will allow us to define those molecular properties that confer distinct pharmacologies on volatile anesthetics. ..

..In summary, these computational studies will provide new knowledge about determinants of alcohol binding and efficacy. ..

..The results may reveal general motifs for action in other systems affected by alcohol and aid in the design of alcohol antagonists. ..

..The results may reveal general motifs for action in other systems affected by alcohol and aid in the design of alcohol antagonists. ..

..subjects with bipolar disorder, major depression, and matched controls. Such outcomes will be significant, because they are expected to identify biochemical mechanisms responsible for abnormal brain development. ..

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..The results of this work will help us to understand how variations in the alpha subunit composition of native GABARs can affect the properties of neurons and their responses to GABA. ..

..Such outcomes will be significant, because they will offer a new treatment for smoking cessation in this vulnerable population. ..

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..Such outcomes will be significant, because they are expected to identify biochemical mechanisms responsible for abnormal brain development in early childhood, as seen in autism. ..

..Such outcomes will be significant, because they will offer a new treatment for smoking cessation in this vulnerable population. ..

..Such outcomes will be significant, because they are expected to identify biochemical mechanisms responsible for abnormal brain development in early childhood, as seen in autism. ..

..In addition, it is expected that the results will provide clues that will lead to fundamental advances in our knowledge of the pathogenesis of schizophrenia and, therefore, of how it can be prevented and treated. ..

..Such outcomes will be significant, because they are expected to identify biochemical mechanisms responsible for abnormal brain development in early childhood, as seen in autism. ..

..An Advisory Committee consisting of established investigators within the Department of Neurology will also be assembled to provide additional guidance. ..

..7) Structural bases for the biophysical properties of recombinant GABAR isoforms that are assembled from GABAR subtypes expressed in hippocampal dentate granule cells. ..

..The non-conserved, missense mutation A322D in the GABA-A receptor alpha 1 subunit gene (GABRA1) is associated with an autosomal dominant form of juvenile myoclonic epilepsy (ADJME)...

..Such an environment maximizes the probability that the principal investigator will establish a scientific niche and embark upon a successful independent academic career. ..

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..7) The NT2 and NT2-N GABAR subtype protein phosphorylated by PKA and PKC. 8) The biophysical mechanisms PKA and PKC modification of NT2 and NT2-N GABAR currents. ..

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..The hypotheses to be tested are: 1) because 11 subunit expression increases throughout development, GABRA1 epilepsy mutations will reduce total GABAAR subunit protein and produce neurons with smaller IPSC amplitudes ..

..In addition, it is expected that the results will provide clues that will lead to fundamental advances in our knowledge of the pathogenesis of schizophrenia and, therefore, of how it can be prevented and treated. ..