Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and intellectual disability (ID), are common diagnoses with highly heterogeneous phenotypes and etiology. The genetics-first approach to research on NDDs has led to the identification of hundreds of genes conferring risk for ASD, ID, and related symptoms. Although relatively few individuals with NDDs share likely gene-disruptive (LGD) mutations in the same gene, characterization of overlapping functions, protein networks, and temporospatial expression patterns among these genes has led to increased understanding of the neurobiological etiology of NDDs. This shift in focus away from single genes and toward broader gene–brain–behavior pathways has been accelerated by the development of publicly available transcriptomic databases, cell type-specific research methods, and sequencing of non-coding genomic regions. The genetics-first approach to research on NDDs has advanced the identification of critical protein function pathways and temporospatial expression patterns, expanding the impact of this research beyond individuals with single-gene mutations to the broader population of patients with NDDs.

中文翻译：

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对神经发育障碍分子遗传学和神经生物学研究进展的遗传学优先方法的思考

神经发育障碍 (NDD)，包括自闭症谱系障碍 (ASD) 和智力障碍 (ID)，是具有高度异质性表型和病因的常见诊断。以遗传学为先的 NDD 研究方法已鉴定出数百个与 ASD、ID 和相关症状相关的基因。尽管相对较少的 NDD 个体在同一基因中具有可能的基因破坏性 (LGD) 突变，但这些基因之间的重叠功能、蛋白质网络和时空表达模式的特征使人们对 NDD 的神经生物学病因有了更多的了解。公开转录组数据库、细胞类型特异性研究方法和非编码基因组区域测序的发展加速了这种焦点从单一基因转向更广泛的基因-大脑-行为途径的转变。以遗传学为先的 NDD 研究方法促进了关键蛋白质功能途径和时空表达模式的识别，将这项研究的影响范围从具有单基因突变的个体扩展到更广泛的 NDD 患者群体。