Forero Diego A, Prada Carlos F, Perry George
Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia.
Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Universidad del Tolima. Ibagué, Colombia.
Open Neurol J. 2016 Nov 11;10:143-148. doi: 10.2174/1874205X01610010143. eCollection 2016.
In recent years, a large number of studies around the world have led to the identification of causal genes for hereditary types of common and rare neurological and psychiatric disorders.
To explore the functional and genomic features of known human genes mutated in neuropsychiatric disorders.
A systematic search was used to develop a comprehensive catalog of genes mutated in neuropsychiatric disorders (NPD). Functional enrichment and protein-protein interaction analyses were carried out. A false discovery rate approach was used for correction for multiple testing.
We found several functional categories that are enriched among NPD genes, such as gene ontologies, protein domains, tissue expression, signaling pathways and regulation by brain-expressed miRNAs and transcription factors. Sixty six of those NPD genes are known to be druggable. Several topographic parameters of protein-protein interaction networks and the degree of conservation between orthologous genes were identified as significant among NPD genes.
These results represent one of the first analyses of enrichment of functional categories of genes known to harbor mutations for NPD. These findings could be useful for a future creation of computational tools for prioritization of novel candidate genes for NPD.
近年来，世界各地的大量研究已鉴定出常见和罕见神经及精神疾病遗传类型的致病基因。
探索在神经精神疾病中发生突变的已知人类基因的功能和基因组特征。
采用系统检索方法建立神经精神疾病（NPD）中突变基因的综合目录。进行功能富集和蛋白质-蛋白质相互作用分析。采用错误发现率方法对多重检验进行校正。
我们发现NPD基因中富集了几个功能类别，如基因本体、蛋白质结构域、组织表达、信号通路以及脑表达的微小RNA和转录因子的调控。已知其中66个NPD基因是可成药的。蛋白质-蛋白质相互作用网络的几个拓扑参数以及直系同源基因之间的保守程度在NPD基因中被确定为显著。
这些结果代表了对已知携带NPD突变的基因功能类别富集的首批分析之一。这些发现可能有助于未来创建计算工具，用于对NPD的新型候选基因进行优先级排序。
