Tabarés-Seisdedos R, Rubenstein J L R
Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, CIBER-SAM, University of Valencia, Valencia, Spain.
Mol Psychiatry. 2009 Jun;14(6):563-89. doi: 10.1038/mp.2009.2. Epub 2009 Feb 10.
Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. 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, PLAT, PPP3CC, SFRP1 and VMAT1/SLC18A1) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, 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, schizophrenia 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.
遗传和发育过程中的缺陷被认为会增加患自闭症和精神分裂症的易感性。据推测，由于病因复杂，确定易感性基因和发育异常一直很困难。然而，8号染色体短臂（8p）区域内的基因对神经精神疾病和癌症的重要性已得到充分证实。8p上有484个注释基因；其中许多很可能是癌基因和肿瘤抑制基因。分子遗传学和发育研究已经在该区域鉴定出21个基因（ADRA1A、ARHGEF10、CHRNA2、CHRNA6、CHRNB3、DKK4、DPYSL2、EGR3、FGF17、FGF20、FGFR1、FZD3、LDL、NAT2、NEF3、NRG1、PCM1、PLAT、PPP3CC、SFRP1和VMAT1/SLC18A1），这些基因最有可能导致神经精神疾病（精神分裂症、自闭症、双相情感障碍和抑郁症）、神经退行性疾病（帕金森病和阿尔茨海默病）和癌症。此外，至少有7种非蛋白质编码RNA（微小RNA）位于8p。8p上的结构变异，如拷贝数变异、微缺失或微重复，也可能导致自闭症、精神分裂症和其他人类疾病，包括癌症。在这篇综述中，我们考虑了细胞遗传学、连锁分析、关联研究、基因表达和内表型研究的现有证据，以探讨这些8p基因在神经精神疾病中的作用。我们还描述了8p基因（Fgf17）中的一个突变如何导致一只小鼠在社交行为的特定组成部分出现缺陷，以及其背内侧前额叶皮质缩小。尽管这些证据存在缺陷，但我们最后讨论了8p与神经精神疾病和癌症的生物学联系。
