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.
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 humanNTNG1 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: Heather I Fraser; Calliope A Dendrou; Barry Healy; Daniel B Rainbow; Sarah Howlett; Luc J Smink; Simon Gregory; Charles A Steward; John A Todd; Laurence B Peterson; Linda S Wicker Journal: J Immunol Date: 2010-04-02 Impact factor: 5.422
Authors: Gilles Maussion; Cristiana Cruceanu; Jill A Rosenfeld; Scott C Bell; Fabrice Jollant; Jin Szatkiewicz; Ryan L Collins; Carrie Hanscom; Ilaria Kolobova; Nicolas Menjot de Champfleur; Ian Blumenthal; Colby Chiang; Vanessa Ota; Christina Hultman; Colm O'Dushlaine; Steve McCarroll; Martin Alda; Sebastien Jacquemont; Zehra Ordulu; Christian R Marshall; Melissa T Carter; Lisa G Shaffer; Pamela Sklar; Santhosh Girirajan; Cynthia C Morton; James F Gusella; Gustavo Turecki; Dimitri J Stavropoulos; Patrick F Sullivan; Stephen W Scherer; Michael E Talkowski; Carl Ernst Journal: Am J Med Genet A Date: 2016-10-19 Impact factor: 2.802
Authors: Tiffany A Greenwood; Laura C Lazzeroni; Monica E Calkins; Robert Freedman; Michael F Green; Raquel E Gur; Ruben C Gur; Gregory A Light; Keith H Nuechterlein; Ann Olincy; Allen D Radant; Larry J Seidman; Larry J Siever; Jeremy M Silverman; William S Stone; Catherine A Sugar; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; David L Braff Journal: Schizophr Res Date: 2015-11-18 Impact factor: 4.939