Supportive evidence for reduced expression of GNB1L in schizophrenia.
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.
Ishiguro
Hiroki
H
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. hishigur@md.tsukuba.ac.jp
Koga
Minori
M
Horiuchi
Yasue
Y
Noguchi
Emiko
E
Morikawa
Miyuki
M
Suzuki
Yoshimi
Y
Arai
Makoto
M
Niizato
Kazuhiro
K
Iritani
Shyuji
S
Itokawa
Masanari
M
Inada
Toshiya
T
Iwata
Nakao
N
Ozaki
Norio
N
Ujike
Hiroshi
H
Kunugi
Hiroshi
H
Sasaki
Tsukasa
T
Takahashi
Makoto
M
Watanabe
Yuichiro
Y
Someya
Toshiyuki
T
Kakita
Akiyoshi
A
Takahashi
Hitoshi
H
Nawa
Hiroyuki
H
Arinami
Tadao
T
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
C434113:GNB1L protein, human; D047908:Intracellular Signaling Peptides and Proteins