Abstract
Since the advent of the chromosome conformation capture technology, our understanding of the human genome 3D organization has grown rapidly and we now know that human interphase chromosomes are folded into multiple layers of hierarchical structures and each layer can play a critical role in transcriptional regulation. Alterations in any one of these finely-tuned layers can lead to unwanted cascade of molecular events and ultimately drive the manifestation of diseases and phenotypes. Here we discuss, starting from chromosome level organization going down to single nucleotide changes, recent studies linking diseases or phenotypes to changes in the 3D genome architecture.