In the personal genome era, an increasing number of variations outside the coding portion of the genome is found. Studies of specific human genetic disorders have been very useful to uncover disease-causing disruptions of the regulatory code, also called "cisruptions". The aim of this project is to identify novel cis-ruptions in three specific developmental disorders. Newly identified cis-ruptions, such as genetic changes in highly conserved non-coding elements, will be validated using in vitro assays (reporter assays; chromosome conformation study) and in vivo assays (zebrafish, mouse). An extensive validation of these genetic defects is of utmost importance before interpreting them in a clinical context. Finally, this CIS-CODE project will contribute to cracking the regulatory code in our gemone, and new cis-ruption mechanisms may serve as a model for other genetic, acquired and complex disorders.