A family-based association study and gene expression analyses of netrin-G1 and-G2 genes in schizophrenia
A family-based association study and gene expression analyses of netrin-G1 and-G2 genes in schizophrenia
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DOI：
10.1016/j.biopsych.2004.11.022
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发表时间：
2005-02-15
影响因子：
10.6
通讯作者：
Yoshikawa, T
中科院分区：
文献类型：
--
作者：
Aoki-Suzuki, M;Yamada, K;Yoshikawa, T
背景资料：netrin-G1（NTNG 1）和-G2（NTNG 2）基因是最近从小鼠中克隆的，在神经元能神经回路的形成和/或维持中起作用。越来越多的证据表明，神经元发育和N-甲基-D-天冬氨酸受体介导的信号系统的紊乱可能是精神分裂症的一个潜在的病理生理机制。因此，我们着手研究人类NTNG 1和NTNG 2的遗传贡献精神分裂症。方法：21个单核苷酸多态性（SNPs）从NTNG 1和10个SNPs从NTNG 2分析了124个精神分裂症家系。所有基因型均采用TaqMan检测。NTNG 1和NTNG 2的表达水平进行了检查，在额叶（布罗德曼区[BA]11和BA 46）和颞叶（BA 22）皮质从精神分裂症和控制死后的大脑。NTNG 1剪接变异体的亚型特异性表达进行了评估，在这些samples.Results：特异性单倍型，包括选择性剪接的NTNG 1外显子与精神分裂症，一致，信使核糖核酸亚型表达显着不同精神分裂症和对照组的大脑。NTNG 2与精神分裂症的相关性也被观察到，SNPs和单倍型聚集在基因的5'区域。结论：NTNG 1和NTNG 2基因可能与精神分裂症的病理生理有关。
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: Specfic 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.