Two isoforms of GABAA receptor β2 subunit with different electrophysiological properties: differential expression and genotypical correlations in schizophrenia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-09-19

AUTHORS

C Zhao, Z Xu, J Chen, Z Yu, K-L Tong, W-S Lo, F W Pun, S-K Ng, S-Y Tsang, H Xue

ABSTRACT

Single nucleotide polymorphisms in type A γ-aminobutyric acid (GABAA) receptor β2 subunit gene (GABRB2) were found to be associated with schizophrenia in Chinese, German, Japanese and Portuguese. To explore potential functional consequences of these DNA sequence polymorphisms, this study examined the expression and electrophysiological properties of two alternatively spliced products of GABRB2 along with genotypical disease association analysis. Real-time quantitative polymerase chain reaction, performed with a cohort of 31 schizophrenics and 31 controls of US population, showed 21.7% reduction in the expression of the long isoform β2L, 13.4% in the short isoform β2S and 15.8% in the sum of the two isoforms β2T in postmortem schizophrenic brain. Furthermore, two independent mRNA quantitation methods showed that the relative expression of the long over the short isoforms was significantly decreased, suggesting the occurrence of altered splicing, in schizophrenia. In male schizophrenics, the heterozygous genotypes of rs1876071 (T/C) and rs1876072 (A/G) were correlated with reduced expression of β2L, β2S and β2T, and the heterozygous of rs2546620 (A/G) and homozygous-minor of rs1876071 (C/C) and rs1876072 (G/G) were correlated with reduced expression of β2T. Significant correlations of expression levels with different alleles and haplotypes were also indicated by quantitative trait analysis. Recombinant GABAA receptors expressed in HEK293 human cells containing β2L underwent a steeper current rundown upon repetitive GABA activation than receptors containing β2S. The results thus revealed genotype-dependent expression of the alternatively spliced isoforms of GABAA receptor β2 subunit, giving rise to electrophysiological consequences that could play an important role in the pathogenesis mechanism of schizophrenia. More... »

PAGES

1092-1105

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.mp.4001899

DOI

http://dx.doi.org/10.1038/sj.mp.4001899

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049554769

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16983389


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Genetics", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Alternative Splicing", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Line", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cohort Studies", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Gene Expression Regulation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Heterozygote", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Homozygote", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Membrane Potentials", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Protein Isoforms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "RNA, Messenger", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptors, GABA-A", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Schizophrenia", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
          "id": "http://www.grid.ac/institutes/grid.24515.37", 
          "name": [
            "Bioengineering Graduate Program, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
            "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zhao", 
        "givenName": "C", 
        "id": "sg:person.01333001006.89", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01333001006.89"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
          "id": "http://www.grid.ac/institutes/grid.24515.37", 
          "name": [
            "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Xu", 
        "givenName": "Z", 
        "id": "sg:person.0731074743.52", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0731074743.52"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
          "id": "http://www.grid.ac/institutes/grid.24515.37", 
          "name": [
            "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chen", 
        "givenName": "J", 
        "id": "sg:person.01335437475.73", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01335437475.73"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Atmospheric, Marine and Coastal Environmental Program, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
          "id": "http://www.grid.ac/institutes/grid.24515.37", 
          "name": [
            "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
            "Atmospheric, Marine and Coastal Environmental Program, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yu", 
        "givenName": "Z", 
        "id": "sg:person.01153375044.92", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01153375044.92"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
          "id": "http://www.grid.ac/institutes/grid.24515.37", 
          "name": [
            "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Tong", 
        "givenName": "K-L", 
        "id": "sg:person.01052164367.49", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01052164367.49"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
          "id": "http://www.grid.ac/institutes/grid.24515.37", 
          "name": [
            "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lo", 
        "givenName": "W-S", 
        "id": "sg:person.01061474417.47", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01061474417.47"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
          "id": "http://www.grid.ac/institutes/grid.24515.37", 
          "name": [
            "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Pun", 
        "givenName": "F W", 
        "id": "sg:person.0621507367.88", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0621507367.88"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
          "id": "http://www.grid.ac/institutes/grid.24515.37", 
          "name": [
            "Bioengineering Graduate Program, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
            "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ng", 
        "givenName": "S-K", 
        "id": "sg:person.01216552406.43", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01216552406.43"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
          "id": "http://www.grid.ac/institutes/grid.24515.37", 
          "name": [
            "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Tsang", 
        "givenName": "S-Y", 
        "id": "sg:person.01177117617.46", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177117617.46"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China", 
          "id": "http://www.grid.ac/institutes/grid.24515.37", 
          "name": [
            "Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Xue", 
        "givenName": "H", 
        "id": "sg:person.013017622740.09", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013017622740.09"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/sj.mp.4001461", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002445384", 
          "https://doi.org/10.1038/sj.mp.4001461"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.mp.4000411", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002412585", 
          "https://doi.org/10.1038/sj.mp.4000411"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.mp.4001434", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048744032", 
          "https://doi.org/10.1038/sj.mp.4001434"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ng1669", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042975627", 
          "https://doi.org/10.1038/ng1669"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00702-005-0338-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045606305", 
          "https://doi.org/10.1007/s00702-005-0338-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/377344a0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045447920", 
          "https://doi.org/10.1038/377344a0"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/bf01734359", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044065382", 
          "https://doi.org/10.1007/bf01734359"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.mp.4001558", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036287924", 
          "https://doi.org/10.1038/sj.mp.4001558"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.mp.4001739", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004137794", 
          "https://doi.org/10.1038/sj.mp.4001739"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/gb-2002-3-7-research0034", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1039751959", 
          "https://doi.org/10.1186/gb-2002-3-7-research0034"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2006-09-19", 
    "datePublishedReg": "2006-09-19", 
    "description": "Single nucleotide polymorphisms in type A \u03b3-aminobutyric acid (GABAA) receptor \u03b22 subunit gene (GABRB2) were found to be associated with schizophrenia in Chinese, German, Japanese and Portuguese. To explore potential functional consequences of these DNA sequence polymorphisms, this study examined the expression and electrophysiological properties of two alternatively spliced products of GABRB2 along with genotypical disease association analysis. Real-time quantitative polymerase chain reaction, performed with a cohort of 31 schizophrenics and 31 controls of US population, showed 21.7% reduction in the expression of the long isoform \u03b22L, 13.4% in the short isoform \u03b22S and 15.8% in the sum of the two isoforms \u03b22T in postmortem schizophrenic brain. Furthermore, two independent mRNA quantitation methods showed that the relative expression of the long over the short isoforms was significantly decreased, suggesting the occurrence of altered splicing, in schizophrenia. In male schizophrenics, the heterozygous genotypes of rs1876071 (T/C) and rs1876072 (A/G) were correlated with reduced expression of \u03b22L, \u03b22S and \u03b22T, and the heterozygous of rs2546620 (A/G) and homozygous-minor of rs1876071 (C/C) and rs1876072 (G/G) were correlated with reduced expression of \u03b22T. Significant correlations of expression levels with different alleles and haplotypes were also indicated by quantitative trait analysis. Recombinant GABAA receptors expressed in HEK293 human cells containing \u03b22L underwent a steeper current rundown upon repetitive GABA activation than receptors containing \u03b22S. The results thus revealed genotype-dependent expression of the alternatively spliced isoforms of GABAA receptor \u03b22 subunit, giving rise to electrophysiological consequences that could play an important role in the pathogenesis mechanism of schizophrenia.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/sj.mp.4001899", 
    "inLanguage": "en", 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1115540", 
        "issn": [
          "1359-4184", 
          "1476-5578"
        ], 
        "name": "Molecular Psychiatry", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "12", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "11"
      }
    ], 
    "keywords": [
      "electrophysiological properties", 
      "reduced expression", 
      "recombinant GABAA receptors", 
      "different electrophysiological properties", 
      "postmortem schizophrenic brains", 
      "GABAA receptor \u03b22 subunit", 
      "real-time quantitative polymerase chain reaction", 
      "GABAA receptor \u03b22", 
      "quantitative polymerase chain reaction", 
      "polymerase chain reaction", 
      "GABAA receptors", 
      "schizophrenic brain", 
      "electrophysiological consequences", 
      "US population", 
      "genotype-dependent expression", 
      "GABA activation", 
      "male schizophrenics", 
      "disease association analysis", 
      "pathogenesis mechanisms", 
      "schizophrenia", 
      "single nucleotide polymorphisms", 
      "chain reaction", 
      "potential functional consequences", 
      "\u03b22 subunit", 
      "significant correlation", 
      "expression levels", 
      "\u03b22 subunit gene", 
      "relative expression", 
      "heterozygous genotype", 
      "functional consequences", 
      "receptors", 
      "schizophrenics", 
      "nucleotide polymorphisms", 
      "differential expression", 
      "expression", 
      "short isoform", 
      "isoforms", 
      "\u03b22", 
      "polymorphism", 
      "human cells", 
      "cohort", 
      "brain", 
      "important role", 
      "subunit gene", 
      "quantitative trait analysis", 
      "genotypical correlations", 
      "heterozygous", 
      "GABRB2", 
      "association analysis", 
      "activation", 
      "altered splicing", 
      "correlation", 
      "quantitation method", 
      "cells", 
      "population", 
      "different alleles", 
      "genotypes", 
      "alleles", 
      "sequence polymorphisms", 
      "levels", 
      "consequences", 
      "control", 
      "haplotypes", 
      "study", 
      "role", 
      "genes", 
      "spliced products", 
      "occurrence", 
      "reduction", 
      "analysis", 
      "mechanism", 
      "subunits", 
      "types", 
      "rise", 
      "results", 
      "steeper", 
      "DNA sequence polymorphisms", 
      "reaction", 
      "trait analysis", 
      "method", 
      "splicing", 
      "products", 
      "properties", 
      "sum", 
      "HEK293 human cells", 
      "aminobutyric acid (GABAA) receptor \u03b22 subunit gene", 
      "acid (GABAA) receptor \u03b22 subunit gene", 
      "receptor \u03b22 subunit gene", 
      "genotypical disease association analysis", 
      "long isoform \u03b22L", 
      "isoform \u03b22L", 
      "\u03b22L", 
      "short isoform \u03b22S", 
      "isoform \u03b22S", 
      "isoforms \u03b22T", 
      "\u03b22T", 
      "independent mRNA quantitation methods", 
      "mRNA quantitation methods", 
      "rs1876071", 
      "heterozygous of rs2546620", 
      "rs2546620", 
      "\u03b22T.", 
      "repetitive GABA activation", 
      "\u03b22S.", 
      "receptor \u03b22 subunit", 
      "receptor \u03b22"
    ], 
    "name": "Two isoforms of GABAA receptor \u03b22 subunit with different electrophysiological properties: differential expression and genotypical correlations in schizophrenia", 
    "pagination": "1092-1105", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1049554769"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/sj.mp.4001899"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "16983389"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/sj.mp.4001899", 
      "https://app.dimensions.ai/details/publication/pub.1049554769"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-01-01T18:16", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220101/entities/gbq_results/article/article_428.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/sj.mp.4001899"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/sj.mp.4001899'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/sj.mp.4001899'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.mp.4001899'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.mp.4001899'


 

This table displays all metadata directly associated to this object as RDF triples.

330 TRIPLES      22 PREDICATES      156 URIs      138 LITERALS      21 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/sj.mp.4001899 schema:about N01ace046f9794bd9b77d1e13497fd56b
2 N0db1b88169b64acd8f3ccab23c27d6ee
3 N2b4ce530176b440bb1c5a91a2740aff7
4 N2b9e91766c024229873f9e7f3e3be401
5 N46955d9062f746e5b79f9da30d32267a
6 N634964bc22d440288f524e0f9d69ec6b
7 N6cd59acc85bf47f58f0d49ef926b361d
8 N78d0f236c9fd4ef7a078e3af1aa340ed
9 Nae246aebf86c4ae888955a2a0ccea5b3
10 Nbd5f30e80a814e718524f8225e8e0241
11 Nc359ca3dec354c51938b8c620612c38a
12 Nc6c7347b9c3749caa3d4b52e26958487
13 Ndd076bdb70e14063af55fa5e16046eba
14 Ndf68aeafa396485a84f1147f9cbedb7d
15 anzsrc-for:06
16 anzsrc-for:0604
17 schema:author N0dc85674d6244228a0e80129ece4e6e4
18 schema:citation sg:pub.10.1007/bf01734359
19 sg:pub.10.1007/s00702-005-0338-9
20 sg:pub.10.1038/377344a0
21 sg:pub.10.1038/ng1669
22 sg:pub.10.1038/sj.mp.4000411
23 sg:pub.10.1038/sj.mp.4001434
24 sg:pub.10.1038/sj.mp.4001461
25 sg:pub.10.1038/sj.mp.4001558
26 sg:pub.10.1038/sj.mp.4001739
27 sg:pub.10.1186/gb-2002-3-7-research0034
28 schema:datePublished 2006-09-19
29 schema:datePublishedReg 2006-09-19
30 schema:description Single nucleotide polymorphisms in type A γ-aminobutyric acid (GABAA) receptor β2 subunit gene (GABRB2) were found to be associated with schizophrenia in Chinese, German, Japanese and Portuguese. To explore potential functional consequences of these DNA sequence polymorphisms, this study examined the expression and electrophysiological properties of two alternatively spliced products of GABRB2 along with genotypical disease association analysis. Real-time quantitative polymerase chain reaction, performed with a cohort of 31 schizophrenics and 31 controls of US population, showed 21.7% reduction in the expression of the long isoform β2L, 13.4% in the short isoform β2S and 15.8% in the sum of the two isoforms β2T in postmortem schizophrenic brain. Furthermore, two independent mRNA quantitation methods showed that the relative expression of the long over the short isoforms was significantly decreased, suggesting the occurrence of altered splicing, in schizophrenia. In male schizophrenics, the heterozygous genotypes of rs1876071 (T/C) and rs1876072 (A/G) were correlated with reduced expression of β2L, β2S and β2T, and the heterozygous of rs2546620 (A/G) and homozygous-minor of rs1876071 (C/C) and rs1876072 (G/G) were correlated with reduced expression of β2T. Significant correlations of expression levels with different alleles and haplotypes were also indicated by quantitative trait analysis. Recombinant GABAA receptors expressed in HEK293 human cells containing β2L underwent a steeper current rundown upon repetitive GABA activation than receptors containing β2S. The results thus revealed genotype-dependent expression of the alternatively spliced isoforms of GABAA receptor β2 subunit, giving rise to electrophysiological consequences that could play an important role in the pathogenesis mechanism of schizophrenia.
31 schema:genre article
32 schema:inLanguage en
33 schema:isAccessibleForFree true
34 schema:isPartOf Nb731ef84a7124276a10de0b48259ea98
35 Nfe63cd61466946e09f36dc0e8584d6ba
36 sg:journal.1115540
37 schema:keywords DNA sequence polymorphisms
38 GABA activation
39 GABAA receptor β2
40 GABAA receptor β2 subunit
41 GABAA receptors
42 GABRB2
43 HEK293 human cells
44 US population
45 acid (GABAA) receptor β2 subunit gene
46 activation
47 alleles
48 altered splicing
49 aminobutyric acid (GABAA) receptor β2 subunit gene
50 analysis
51 association analysis
52 brain
53 cells
54 chain reaction
55 cohort
56 consequences
57 control
58 correlation
59 different alleles
60 different electrophysiological properties
61 differential expression
62 disease association analysis
63 electrophysiological consequences
64 electrophysiological properties
65 expression
66 expression levels
67 functional consequences
68 genes
69 genotype-dependent expression
70 genotypes
71 genotypical correlations
72 genotypical disease association analysis
73 haplotypes
74 heterozygous
75 heterozygous genotype
76 heterozygous of rs2546620
77 human cells
78 important role
79 independent mRNA quantitation methods
80 isoform β2L
81 isoform β2S
82 isoforms
83 isoforms β2T
84 levels
85 long isoform β2L
86 mRNA quantitation methods
87 male schizophrenics
88 mechanism
89 method
90 nucleotide polymorphisms
91 occurrence
92 pathogenesis mechanisms
93 polymerase chain reaction
94 polymorphism
95 population
96 postmortem schizophrenic brains
97 potential functional consequences
98 products
99 properties
100 quantitation method
101 quantitative polymerase chain reaction
102 quantitative trait analysis
103 reaction
104 real-time quantitative polymerase chain reaction
105 receptor β2
106 receptor β2 subunit
107 receptor β2 subunit gene
108 receptors
109 recombinant GABAA receptors
110 reduced expression
111 reduction
112 relative expression
113 repetitive GABA activation
114 results
115 rise
116 role
117 rs1876071
118 rs2546620
119 schizophrenia
120 schizophrenic brain
121 schizophrenics
122 sequence polymorphisms
123 short isoform
124 short isoform β2S
125 significant correlation
126 single nucleotide polymorphisms
127 spliced products
128 splicing
129 steeper
130 study
131 subunit gene
132 subunits
133 sum
134 trait analysis
135 types
136 β2
137 β2 subunit
138 β2 subunit gene
139 β2L
140 β2S.
141 β2T
142 β2T.
143 schema:name Two isoforms of GABAA receptor β2 subunit with different electrophysiological properties: differential expression and genotypical correlations in schizophrenia
144 schema:pagination 1092-1105
145 schema:productId N255dc3fd1d82472ea3c769a339e98dcd
146 N96d5e1bde8244a10bbed54f1980a34df
147 Nf31e33e4ee2f41f6b986513010d884ed
148 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049554769
149 https://doi.org/10.1038/sj.mp.4001899
150 schema:sdDatePublished 2022-01-01T18:16
151 schema:sdLicense https://scigraph.springernature.com/explorer/license/
152 schema:sdPublisher N5e7e734812854e568c817165f5d8b1ca
153 schema:url https://doi.org/10.1038/sj.mp.4001899
154 sgo:license sg:explorer/license/
155 sgo:sdDataset articles
156 rdf:type schema:ScholarlyArticle
157 N01ace046f9794bd9b77d1e13497fd56b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
158 schema:name RNA, Messenger
159 rdf:type schema:DefinedTerm
160 N04fbae0ba77b457789e2b152b5ffa638 rdf:first sg:person.0621507367.88
161 rdf:rest Nd9ccb219a466444599a3abcc21ac5afe
162 N0db1b88169b64acd8f3ccab23c27d6ee schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
163 schema:name Homozygote
164 rdf:type schema:DefinedTerm
165 N0dc85674d6244228a0e80129ece4e6e4 rdf:first sg:person.01333001006.89
166 rdf:rest N51a31c6a81a04bc0aae987b115dd02ae
167 N22eefeac05164d8c9ce8eeb45b5fa56a rdf:first sg:person.01153375044.92
168 rdf:rest N5c5572c729d947a2a3aef4bd51f83875
169 N255dc3fd1d82472ea3c769a339e98dcd schema:name dimensions_id
170 schema:value pub.1049554769
171 rdf:type schema:PropertyValue
172 N29d677e10370404489d572580de2c67c rdf:first sg:person.01061474417.47
173 rdf:rest N04fbae0ba77b457789e2b152b5ffa638
174 N2b4ce530176b440bb1c5a91a2740aff7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
175 schema:name Protein Isoforms
176 rdf:type schema:DefinedTerm
177 N2b9e91766c024229873f9e7f3e3be401 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
178 schema:name Cell Line
179 rdf:type schema:DefinedTerm
180 N3c3acd46ea7e475f8756a0fbd961859d rdf:first sg:person.01177117617.46
181 rdf:rest N5c0a0751f3854831a9cf47bf9acdf7ab
182 N46955d9062f746e5b79f9da30d32267a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
183 schema:name Alternative Splicing
184 rdf:type schema:DefinedTerm
185 N51a31c6a81a04bc0aae987b115dd02ae rdf:first sg:person.0731074743.52
186 rdf:rest Na34d39f347ed482db098b53f5a367376
187 N5c0a0751f3854831a9cf47bf9acdf7ab rdf:first sg:person.013017622740.09
188 rdf:rest rdf:nil
189 N5c5572c729d947a2a3aef4bd51f83875 rdf:first sg:person.01052164367.49
190 rdf:rest N29d677e10370404489d572580de2c67c
191 N5e7e734812854e568c817165f5d8b1ca schema:name Springer Nature - SN SciGraph project
192 rdf:type schema:Organization
193 N634964bc22d440288f524e0f9d69ec6b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
194 schema:name Schizophrenia
195 rdf:type schema:DefinedTerm
196 N6cd59acc85bf47f58f0d49ef926b361d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
197 schema:name Cohort Studies
198 rdf:type schema:DefinedTerm
199 N78d0f236c9fd4ef7a078e3af1aa340ed schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
200 schema:name Heterozygote
201 rdf:type schema:DefinedTerm
202 N96d5e1bde8244a10bbed54f1980a34df schema:name doi
203 schema:value 10.1038/sj.mp.4001899
204 rdf:type schema:PropertyValue
205 Na34d39f347ed482db098b53f5a367376 rdf:first sg:person.01335437475.73
206 rdf:rest N22eefeac05164d8c9ce8eeb45b5fa56a
207 Nae246aebf86c4ae888955a2a0ccea5b3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
208 schema:name Membrane Potentials
209 rdf:type schema:DefinedTerm
210 Nb731ef84a7124276a10de0b48259ea98 schema:volumeNumber 11
211 rdf:type schema:PublicationVolume
212 Nbd5f30e80a814e718524f8225e8e0241 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
213 schema:name Gene Expression Regulation
214 rdf:type schema:DefinedTerm
215 Nc359ca3dec354c51938b8c620612c38a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
216 schema:name Male
217 rdf:type schema:DefinedTerm
218 Nc6c7347b9c3749caa3d4b52e26958487 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
219 schema:name Receptors, GABA-A
220 rdf:type schema:DefinedTerm
221 Nd9ccb219a466444599a3abcc21ac5afe rdf:first sg:person.01216552406.43
222 rdf:rest N3c3acd46ea7e475f8756a0fbd961859d
223 Ndd076bdb70e14063af55fa5e16046eba schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
224 schema:name Female
225 rdf:type schema:DefinedTerm
226 Ndf68aeafa396485a84f1147f9cbedb7d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
227 schema:name Humans
228 rdf:type schema:DefinedTerm
229 Nf31e33e4ee2f41f6b986513010d884ed schema:name pubmed_id
230 schema:value 16983389
231 rdf:type schema:PropertyValue
232 Nfe63cd61466946e09f36dc0e8584d6ba schema:issueNumber 12
233 rdf:type schema:PublicationIssue
234 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
235 schema:name Biological Sciences
236 rdf:type schema:DefinedTerm
237 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
238 schema:name Genetics
239 rdf:type schema:DefinedTerm
240 sg:journal.1115540 schema:issn 1359-4184
241 1476-5578
242 schema:name Molecular Psychiatry
243 schema:publisher Springer Nature
244 rdf:type schema:Periodical
245 sg:person.01052164367.49 schema:affiliation grid-institutes:grid.24515.37
246 schema:familyName Tong
247 schema:givenName K-L
248 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01052164367.49
249 rdf:type schema:Person
250 sg:person.01061474417.47 schema:affiliation grid-institutes:grid.24515.37
251 schema:familyName Lo
252 schema:givenName W-S
253 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01061474417.47
254 rdf:type schema:Person
255 sg:person.01153375044.92 schema:affiliation grid-institutes:grid.24515.37
256 schema:familyName Yu
257 schema:givenName Z
258 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01153375044.92
259 rdf:type schema:Person
260 sg:person.01177117617.46 schema:affiliation grid-institutes:grid.24515.37
261 schema:familyName Tsang
262 schema:givenName S-Y
263 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01177117617.46
264 rdf:type schema:Person
265 sg:person.01216552406.43 schema:affiliation grid-institutes:grid.24515.37
266 schema:familyName Ng
267 schema:givenName S-K
268 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01216552406.43
269 rdf:type schema:Person
270 sg:person.013017622740.09 schema:affiliation grid-institutes:grid.24515.37
271 schema:familyName Xue
272 schema:givenName H
273 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013017622740.09
274 rdf:type schema:Person
275 sg:person.01333001006.89 schema:affiliation grid-institutes:grid.24515.37
276 schema:familyName Zhao
277 schema:givenName C
278 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01333001006.89
279 rdf:type schema:Person
280 sg:person.01335437475.73 schema:affiliation grid-institutes:grid.24515.37
281 schema:familyName Chen
282 schema:givenName J
283 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01335437475.73
284 rdf:type schema:Person
285 sg:person.0621507367.88 schema:affiliation grid-institutes:grid.24515.37
286 schema:familyName Pun
287 schema:givenName F W
288 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0621507367.88
289 rdf:type schema:Person
290 sg:person.0731074743.52 schema:affiliation grid-institutes:grid.24515.37
291 schema:familyName Xu
292 schema:givenName Z
293 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0731074743.52
294 rdf:type schema:Person
295 sg:pub.10.1007/bf01734359 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044065382
296 https://doi.org/10.1007/bf01734359
297 rdf:type schema:CreativeWork
298 sg:pub.10.1007/s00702-005-0338-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045606305
299 https://doi.org/10.1007/s00702-005-0338-9
300 rdf:type schema:CreativeWork
301 sg:pub.10.1038/377344a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045447920
302 https://doi.org/10.1038/377344a0
303 rdf:type schema:CreativeWork
304 sg:pub.10.1038/ng1669 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042975627
305 https://doi.org/10.1038/ng1669
306 rdf:type schema:CreativeWork
307 sg:pub.10.1038/sj.mp.4000411 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002412585
308 https://doi.org/10.1038/sj.mp.4000411
309 rdf:type schema:CreativeWork
310 sg:pub.10.1038/sj.mp.4001434 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048744032
311 https://doi.org/10.1038/sj.mp.4001434
312 rdf:type schema:CreativeWork
313 sg:pub.10.1038/sj.mp.4001461 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002445384
314 https://doi.org/10.1038/sj.mp.4001461
315 rdf:type schema:CreativeWork
316 sg:pub.10.1038/sj.mp.4001558 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036287924
317 https://doi.org/10.1038/sj.mp.4001558
318 rdf:type schema:CreativeWork
319 sg:pub.10.1038/sj.mp.4001739 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004137794
320 https://doi.org/10.1038/sj.mp.4001739
321 rdf:type schema:CreativeWork
322 sg:pub.10.1186/gb-2002-3-7-research0034 schema:sameAs https://app.dimensions.ai/details/publication/pub.1039751959
323 https://doi.org/10.1186/gb-2002-3-7-research0034
324 rdf:type schema:CreativeWork
325 grid-institutes:grid.24515.37 schema:alternateName Atmospheric, Marine and Coastal Environmental Program, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China
326 Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China
327 schema:name Atmospheric, Marine and Coastal Environmental Program, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China
328 Bioengineering Graduate Program, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China
329 Department of Biochemistry and Applied Genomics Laboratory, Hong Kong University of Science & Technology, Clear Water Bay, Hong Kong, China
330 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...