Imprinting in the schizophrenia candidate gene GABRB2 encoding GABAA receptor β2 subunit

Pun, Frank W.; Zhao, Cunyou; Lo, Woo-Kuen; Ng, Siu Kin; Tsang, Suk Ying; Nimgaonkar, Vishwajit L.; Chung, Wen-Yu; Ungvári, Gábor S.; Xue, Hong

doi:10.1038/mp.2010.47

Cited by 50 publications

(36 citation statements)

References 47 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, our transcriptome analysis exposed CP-enriched genes and splice isoforms involved in the maturation programs, including dendritic growth, synaptogenesis, exocytosis, and axonogenesis. Furthermore, our analysis uncovered genes associated with tumorigenesis (Sox11) (50), mental retardation (Kirrel3) (51), and schizophrenia (Gabrb2) (52), but their contribution to normal differentiation and signaling processes in the cortex is not yet understood.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing

Ayoub¹,

Xie³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

131

128

View full text Add to dashboard Cite

Characterizing the genetic programs that specify development and evolution of the cerebral cortex is a central challenge in neuroscience. Stem cells in the transient embryonic ventricular and subventricular zones generate neurons that migrate across the intermediate zone to the overlying cortical plate, where they differentiate and form the neocortex. It is clear that not one but a multitude of molecular pathways are necessary to progress through each cellular milestone, yet the underlying transcriptional programs remain unknown. Here, we apply differential transcriptome analysis on microscopically isolated cell populations, to define five transcriptional programs that represent each transient embryonic zone and the progression between these zones. The five transcriptional programs contain largely uncharacterized genes in addition to transcripts necessary for stem cell maintenance, neurogenesis, migration, and differentiation. Additionally, we found intergenic transcriptionally active regions that possibly encode unique zone-specific transcripts. Finally, we present a highresolution transcriptome map of transient zones in the embryonic mouse forebrain.radial glia | pyramidal neurons | cortical development | laser microdissection

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing

Ayoub¹,

Xie³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

131

128

View full text Add to dashboard Cite

show abstract

“…In common with the majority of the epilepsy mutations, many recently described SNPs lead to protein changes that appear to impair the delivery of functional receptors to the cell surface, compromising normal inhibition. For example, hypermethylation occurs in the vicinity of one schizophrenia-associated SNP, and two other SNPs introduce a CpG methylation site (Pun et al, 2011). In both cases, studies of trios indicated that these SNPs, and hence aberrant methylation, may play a role in GABRB2 imprinting and the risk of developing schizophrenia.…”

Section: Gaba a Receptorsmentioning

confidence: 99%

“…GABRB2 can be expressed as a long or short alternative RNA splice variant. Notably, the short isoform lacks exon 10, which encodes residues that form a consensus phosphorylation site for calmodulin protein kinase II (Thr365), which might play a role in receptor retention in the membrane (Pun et al, 2011). Two schizophrenia-linked SNPs reduce the amount of the longer isoform in favor of the shorter, less stable isoform.…”

Section: Gaba a Receptorsmentioning

confidence: 99%

Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

Yuan¹,

Low²,

Moody³

et al. 2015

Mol Pharmacol

186

176

View full text Add to dashboard Cite

The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-D-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases.

show abstract

“…In this context, two www.intechopen.com mental disorders stand out: schizophrenia and bipolar disorder (Basset et al, 2003;Craddock et al, 2010;Pun et al, 2011). Nevertheless, to establish a possible causal relation it is necessary to deepen the study of several issues.…”

Section: Behavioral Phenotype and Psychiatric Phenotypementioning

confidence: 99%

Mood Disorders in Individuals with Genetic Syndromes and Intellectual Disability

Teixeira¹,

Mesquita²,

Araújo³

et al. 2012

Clinical, Research and Treatment Approaches to Affective Disorders

View full text Add to dashboard Cite

Imprinting in the schizophrenia candidate gene GABRB2 encoding GABAA receptor β2 subunit

Cited by 50 publications

References 47 publications

Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing

Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing

Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

Mood Disorders in Individuals with Genetic Syndromes and Intellectual Disability

Contact Info

Product

Resources

About