論文

査読有り 国際誌
2006年6月

Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar 1 disorder: relevance to neuronal network perturbation

HUMAN MOLECULAR GENETICS
  • Noriaki Nakatani
  • Eiji Hattori
  • Tetsuo Ohnishi
  • Brian Dean
  • Yoshimi Iwayama
  • Izuru Matsumoto
  • Tadafumi Kato
  • Noriko Osumi
  • Teruhiko Higuchi
  • Shin-ichi Niwa
  • Takeo Yoshikawa
  • 全て表示

15
12
開始ページ
1949
終了ページ
1962
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1093/hmg/ddl118
出版者・発行元
OXFORD UNIV PRESS

The limited number of genome-wide transcriptome analyses using the postmortem brains of bipolar disorder sufferers has not produced a clear consensus on the molecular pathways affected by the disorder. To expand the knowledge in this area, we examined the expression levels of more than 12 000 genes in Brodmann's Area (BA), 46 (dorsolateral prefrontal cortex) from bipolar I disorder and control samples using Affymetrix GeneChips. This analysis detected 108 differentially expressed genes in bipolar brains. Validation studies using quantitative RT-PCR on the two original diagnostic cohorts plus tissue from schizophrenic subjects, confirmed the differential expressions of eight genes (RAP1GA1, SST, HLA-DRA, KATNB1, PURA, NDUFV2, STAR and PAFAH1B3) in a bipolar-specific manner and one gene (CCL3) which was downregulated in both bipolar and schizophrenic brains. Of these, protein levels of RAP1GA1 (RAP1 GTPase activating protein 1) showed a trend of increase in BA46 from bipolar brains, in keeping with mRNA transcript levels. Transmission disequilibrium analysis of the nine genes using 43 single nucleotide polymorphisms (SNPs) in 229 National Institute of Mental Health bipolar trios exposed nominal SNP association and modest empirical haplotypic association (P = 0.033) between SST(somatostatin) and disease. Finally, gene network analysis using the currently obtained expression data highlighted cellular growth and nervous system development pathways as potential targets in the molecular pathophysiology of bipolar disorder.

リンク情報
DOI
https://doi.org/10.1093/hmg/ddl118
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/16687443
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000238613900003&DestApp=WOS_CPL
ID情報
  • DOI : 10.1093/hmg/ddl118
  • ISSN : 0964-6906
  • eISSN : 1460-2083
  • PubMed ID : 16687443
  • Web of Science ID : WOS:000238613900003

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