人类基因组由数百万对碱基组成，是生命的蓝图，编码细胞过程的指令。然而，基因组不仅仅是线性序列；而且是线性序列。相反，DNA 和组蛋白的复合物（称为染色质）在各个层面上表现出复杂的组织，这深刻地影响着基因表达和细胞功能。了解基因组组织的核心是三维 (3D) 基因组研究的新兴领域。利用 Hi-C 等先进技术，研究人员揭示了基因组元件的非随机配置，强调了它们在转录调控和疾病机制中的重要性。拓扑关联结构域 (TAD) 划分了具有优先内部相互作用的染色质区域，在基因调控中发挥着至关重要的作用，并且越来越多地与癌症和精神分裂症等各种疾病有关。然而，它们在神经发育障碍（NDD）中的作用仍然知之甚少。在这里，我们重点关注 NDD 中跨进化和细胞类型之间的 TAD 和 3D 保守。对基因组组织及其对疾病影响的研究在理解 ASD（自闭症谱系障碍）等 NDD 病因学方面取得了重大突破。通过阐明自闭症谱系障碍的广泛表现，研究人员旨在揭示导致其异质性的潜在遗传和表观遗传因素。此外，将 TAD 破坏与 NDD 联系起来的研究强调了空间基因组组织在维持大脑正常发育和功能方面的重要性。总之，这篇综述强调了基因组组织、转录控制和疾病病理学之间错综复杂的相互作用，揭示了基本的生物过程，并提供了对 ASD 等 NDD 背后机制的见解。© 2024。作者获得独家许可德国施普林格出版社 (Springer-Verlag GmbH)，隶属于施普林格自然集团。

The human genome, comprising millions of pairs of bases, serves as the blueprint of life, encoding instructions for cellular processes. However, genomes are not merely linear sequences; rather, the complex of DNA and histones, known as chromatin, exhibits complex organization across various levels, which profoundly influence gene expression and cellular function. Central to understanding genome organization is the emerging field of three-dimensional (3D) genome studies. Utilizing advanced techniques such as Hi-C, researchers have unveiled non-random dispositions of genomic elements, highlighting their importance in transcriptional regulation and disease mechanisms. Topologically Associating Domains (TADs), that demarcate regions of chromatin with preferential internal interactions, play crucial roles in gene regulation and are increasingly implicated in various diseases such as cancer and schizophrenia. However, their role in Neurodevelopmental Disorders (NDDs) remains poorly understood. Here, we focus on TADs and 3D conservation across the evolution and between cell types in NDDs. The investigation into genome organization and its impact on disease has led to significant breakthroughs in understanding NDDs etiology such ASD (Autism Spectrum Disorder). By elucidating the wide spectrum of ASD manifestations, researchers aim to uncover the underlying genetic and epigenetic factors contributing to its heterogeneity. Moreover, studies linking TAD disruption to NDDs underscore the importance of spatial genome organization in maintaining proper brain development and function. In summary, this review highlights the intricate interplay between genome organization, transcriptional control, and disease pathology, shedding light on fundamental biological processes and offering insights into the mechanisms underlying NDDs like ASD.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.