Breaking TADs: How Alterations of Chromatin Domains Result in Disease

Spatial organization is an inherent property of the vertebrate genome to accommodate the roughly 2 m of DNA in the nucleus of a cell. In this nonrandom organization, topologically associating domains (TADs) emerge as a fundamental structural unit that is thought to guide regulatory elements to their cognate promoters. In this review we summarize the most recent findings about TADs and the boundary regions separating them. We discuss how the disruption of these structures by genomic rearrangements can result in gene misexpression and disease.

TrendsChromosome conformation capture techniques have enabled scientists to study the 3D organization of the genome, identifying topologically associating domains (TADs) as fundamental regulatory units of the genome.TADs and their boundary regions are critical for correct gene expression and their disruption can cause disease.TAD maps of the human genome allow better prediction of the effects of structural variations.CRISPR/Cas technology can be used to model human structural variants and understand their pathomechanisms.