Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
CNR Institute of Neuroscience, 20129 Milan, Italy.
Biomolecules. 2021 Nov 17;11(11):1713. doi: 10.3390/biom11111713.
The advent of next-generation sequencing (NGS) is heavily changing both the diagnosis of human conditions and basic biological research. It is now possible to dig deep inside the genome of hundreds of thousands or even millions of people and find both common and rare genomic variants and to perform detailed phenotypic characterizations of both physiological organs and experimental models. Recent years have seen the introduction of multiple techniques using NGS to profile transcription, DNA and chromatin modifications, protein binding, etc., that are now allowing us to profile cells in bulk or even at a single-cell level. Although rare and ultra-rare diseases only affect a few people, each of these diseases represent scholarly cases from which a great deal can be learned about the pathological and physiological function of genes, pathways, and mechanisms. Therefore, for rare diseases, state-of-the-art investigations using NGS have double valence: their genomic cause (new variants) and the characterize the underlining the mechanisms associated with them (discovery of gene function) can be found. In a non-exhaustive manner, this review will outline the main usage of NGS-based techniques for the diagnosis and characterization of neurodevelopmental disorders (NDDs), under whose umbrella many rare and ultra-rare diseases fall.
下一代测序（NGS）的出现正在极大地改变人类疾病的诊断和基础生物学研究。现在，我们可以深入研究数十万人甚至数百万人的基因组，发现常见和罕见的基因组变异，并对生理器官和实验模型进行详细的表型特征描述。近年来，已经引入了多种使用 NGS 进行转录组、DNA 和染色质修饰、蛋白质结合等分析的技术，这些技术现在使我们能够对大量细胞甚至单细胞进行分析。尽管罕见和超罕见疾病仅影响少数人，但每种疾病都是一个学术案例，可以从中了解基因、途径和机制的病理和生理功能。因此，对于罕见疾病，使用 NGS 的最先进的研究具有双重价值：可以找到其基因组原因（新变异）以及与之相关的潜在机制（发现基因功能）。本文以非穷尽的方式概述了基于 NGS 的技术在神经发育障碍（NDD）的诊断和特征描述中的主要应用，许多罕见和超罕见疾病都属于这一范畴。
