A precise three-dimensional (3D) organization of chromatin is central to achieve the intricate transcriptional patterns that are required to form complex organisms. Growing evidence supports an important role of 3D chromatin architecture in development and delineates its alterations as prominent causes of disease. In this review, we discuss emerging concepts on the fundamental forces shaping genomes in space and on how their disruption can lead to pathogenic phenotypes. We describe the molecular mechanisms underlying a wide range of diseases, from the systemic effects of coding mutations on 3D architectural factors, to the more tissue-specific phenotypes resulting from genetic and epigenetic modifications at specific loci. Understanding the connection between the 3D organization of the genome and its underlying biological function will allow a better interpretation of human pathogenesis.

中文翻译：

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秩序与失调：人类疾病中3D染色质组织异常。

染色质的精确三维（3D）组织对于实现形成复杂生物所需的复杂转录模式至关重要。越来越多的证据支持3D染色质结构在发育中的重要作用，并将其改变描述为疾病的重要原因。在这篇综述中，我们讨论了在空间上塑造基因组的基本力及其破坏如何导致致病表型的新兴概念。我们描述了范围广泛的疾病的分子机制，从对3D建筑因素的编码突变的全身效应，到在特定基因座的遗传和表观遗传修饰产生的组织特异性表型。