The 3D genome in medicine: Technological advances, disease mechanisms, and translational challenges

Three-dimensional (3D) genome organization has reshaped our understanding of human disease by revealing regulatory mechanisms that cannot be explained by the linear genome alone. Rapid advances in chromosome-conformation technologies, single-cell genomics, spatial multi-omics and artificial intelligence have enabled increasingly precise characterization of genome architecture and uncovered common principles of chromatin dysregulation across diverse diseases. However, translating these discoveries into clinical practice remains challenging because of limited causal evidence, functional validation and standardized analytical frameworks. This review discusses recent technological advances in medical 3D genomics, summarizes the shared mechanisms of chromatin dysregulation in human diseases, and highlights emerging opportunities for molecular diagnosis, variant interpretation and therapeutic target discovery. It further examines the major challenges that must be overcome before genome architecture can be routinely integrated into precision medicine.