| Abstract |
Defects in genetic and developmental processes are thought to contribute susceptibility to autism and精神分裂症. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20, FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1,平台, PPP3CC, SFRP1 and VMAT1/SLC18A1) that are most likely to contribute to neuropsychiatric disorders (精神分裂症, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson's and Alzheimer's disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism,精神分裂症and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (Fgf17) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence. |
| Abstract |
As精神分裂症-like symptoms are produced by administration of phencyclidine (PCP), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, PCP-responsive genes could be involved in the pathophysiology of精神分裂症. We injected PCP to Wistar rats and isolated five different parts of the brain in 1 and 4?hr after the injection. We analyzed the gene expression induced by the PCP treatment of these tissues using the AGILENT rat cDNA microarray system. We observed changes in expression level in 90 genes and 21 ESTs after the treatment. Out of the 10 genes showing >2-fold expressional change evaluated by qRT-PCR, we selected 7 genes as subjects for the locus-wide association study to identify susceptibility genes for精神分裂症in the Japanese population. In haplotype analysis, significant associations were detected in combinations of two SNPs of BTG2 (P?=?1.4?�?10(-6) ), PDE4A (P?=?1.4?�?10(-6) ), and平台(P?=?1?�?10(-3) ), after false discovery rate (FDR) correction. Additionally, we not only successfully replicated the haplotype associations in PDE4A (P?=?6.8?�?10(-12) ) and平台(P?=?0.015), but also detected single-point associations of one SNP in PDE4A (P?=?0.0068) and two SNPs in平台(P?=?0.0260 and 0.0104) in another larger sample set consisting of 2,224 cases and 2,250 controls. These results indicate that PDE4A and平台may be susceptibility genes for精神分裂症in the Japanese population. |