Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, United States of America.
Bioinformatics and Genomics Program, Pennsylvania State University, University Park, Pennsylvania, United States of America.
PLoS Genet. 2019 Jan 17;15(1):e1007879. doi: 10.1371/journal.pgen.1007879. eCollection 2019 Jan.
Variably expressive copy-number variants (CNVs) are characterized by extensive phenotypic heterogeneity of neuropsychiatric phenotypes. Approaches to identify single causative genes for these phenotypes within each CNV have not been successful. Here, we posit using multiple lines of evidence, including pathogenicity metrics, functional assays of model organisms, and gene expression data, that multiple genes within each CNV region are likely responsible for the observed phenotypes. We propose that candidate genes within each region likely interact with each other through shared pathways to modulate the individual gene phenotypes, emphasizing the genetic complexity of CNV-associated neuropsychiatric features.
变异性表达的拷贝数变异 (CNVs) 以神经精神表型的广泛表型异质性为特征。在每个 CNV 中识别这些表型的单一致病基因的方法尚未成功。在这里,我们假设使用多种证据,包括致病性指标、模式生物的功能测定和基因表达数据,每个 CNV 区域内的多个基因可能负责观察到的表型。我们提出,每个区域内的候选基因可能通过共享途径相互作用,以调节个体基因表型,强调与 CNV 相关的神经精神特征的遗传复杂性。