Modeling three-dimensional genomic organization in evolution and pathogenesis

The regulation of gene expression is mediated via the complex three-dimensional (3D) conformation of the genetic material and its interactions with various intracellular factors. Various experimental and computational approaches have been developed in recent years for understating the relation between the 3D conformation of the genome and the phenotypes of cells in normal condition and diseases. In this review, we will discuss novel approaches for analyzing and modeling the 3D genomic conformation, focusing on deciphering disease-causing mutations that affect gene expression. We conclude that as this is a very challenging mission, an important direction should involve the comparative analysis of various 3D models from various organisms or cells.