title: A family-based association study and gene expression analyses of netrin-G1 and -G2 genes in schizophrenia.
abstract: BACKGROUND
  The netrin-G1 (NTNG1) and -G2 (NTNG2) genes, recently cloned from mouse, play a role in the formation and/or maintenance of glutamatergic neural circuitry. Accumulating evidence strongly suggests that disturbances of neuronal development and the N-methyl-d-aspartate receptor-mediated signaling system might represent a potential pathophysiology in schizophrenia. We therefore set out to examine the genetic contribution of human NTNG1 and NTNG2 to schizophrenia.
  
  
  METHODS
  Twenty-one single nucleotide polymorphisms (SNPs) from NTNG1 and 10 SNPs from NTNG2 were analyzed in 124 schizophrenic pedigrees. All genotypes were determined with the TaqMan assay. The expression levels of NTNG1 and NTNG2 were examined in the frontal (Brodmann's Area [BA]11 and BA46) and temporal (BA22) cortices from schizophrenic and control postmortem brains. The isoform-specific expression of NTNG1 splice variants was assessed in these samples.
  
  
  RESULTS
  Specific haplotypes encompassing alternatively spliced exons of NTNG1 were associated with schizophrenia, and concordantly, messenger ribonucleic acid isoform expression was significantly different between schizophrenic and control brains. An association between NTNG2 and schizophrenia was also observed with SNPs and haplotypes that clustered in the 5' region of the gene.
  
  
  CONCLUSIONS
  The NTNG1 and NTNG2 genes might be relevant to the pathophysiology of schizophrenia.
authors.affiliation: Laboratories for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Aoki-Suzuki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Joanne
authors.initials: J
authors.lastname: Meerabux
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama-Shigeno
authors.forename: Hisako
authors.initials: H
authors.lastname: Ohba
authors.forename: Kazuya
authors.initials: K
authors.lastname: Iwamoto
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takao
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Suto
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nakatani
authors.forename: Brian
authors.initials: B
authors.lastname: Dean
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nishimura
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Seki
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Kato
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Toru
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D005091:Exons; D005192:Family Health; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000379:methods; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008297:Male; D051379:Mice; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000075385:Netrins; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075385:Netrins; D020033:Protein Isoforms; D012333:RNA, Messenger; C413653:netrin-G1; C088894:netrin-2