title: Supportive evidence for reduced expression of GNB1L in schizophrenia.
abstract: BACKGROUND
  Chromosome 22q11 deletion syndrome (22q11DS) increases the risk of development of schizophrenia more than 10 times compared with that of the general population, indicating that haploinsufficiency of a subset of the more than 20 genes contained in the 22q11DS region could increase the risk of schizophrenia. In the present study, we screened for genes located in the 22q11DS region that are expressed at lower levels in postmortem prefrontal cortex of patients with schizophrenia than in those of controls.
  
  
  METHODS
  Gene expression was screened by Illumina Human-6 Expression BeadChip arrays and confirmed by real-time reverse transcription-polymerase chain reaction assays and Western blot analysis.
  
  
  RESULTS
  Expression of GNB1L was lower in patients with schizophrenia than in control subjects in both Australian (10 schizophrenia cases and 10 controls) and Japanese (43 schizophrenia cases and 11 controls) brain samples. TBX1 could not be evaluated due to its low expression levels. Expression levels of the other genes were not significantly lower in patients with schizophrenia than in control subjects. Association analysis of tag single-nucleotide polymorphisms in the GNB1L gene region did not confirm excess homozygosity in 1918 Japanese schizophrenia cases and 1909 Japanese controls. Haloperidol treatment for 50 weeks increased Gnb1l gene expression in prefrontal cortex of mice.
  
  
  CONCLUSIONS
  Taken together with the impaired prepulse inhibition observed in heterozygous Gnb1l knockout mice reported by the previous study, the present findings support assertions that GNB1L is one of the genes in the 22q11DS region responsible for increasing the risk of schizophrenia.
authors.affiliation: Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. hishigur@md.tsukuba.ac.jp
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Minori
authors.initials: M
authors.lastname: Koga
authors.forename: Yasue
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Emiko
authors.initials: E
authors.lastname: Noguchi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Morikawa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Niizato
authors.forename: Shyuji
authors.initials: S
authors.lastname: Iritani
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nawa
authors.forename: Tadao
authors.initials: T
authors.lastname: Arinami
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D003431:Cross-Cultural Comparison; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012565:Schizophrenic Psychology
chemical_list: C434113:GNB1L protein, human; D047908:Intracellular Signaling Peptides and Proteins