The variability of the human genome sequence and structure has recently been found to be between 10 and 100-fold higher than previous estimations. The concept of a unique human genome structure has been proven to be wrong and the challenge now is to determine the complete structural variability and organization of the human genome in several populations, and to establish their relationships with human diseases and common traits. The European population has a long history, is extremely rich in genetic variability, and has left many marks in its diverse geographic regions, which have materialised in different disease prevalences and phenotypes. This programme aims to study the structural variability of European citizens at the sequence level, with a special focus on common human disorders and traits and with an integration of epidemiology and preventive measures. This goal will be achieved by: a) the integration of population/geographic data; b) the analysis of epidemiological aspects of human disease and common traits; c) the use of high-throughput biology technologies to dissect the human genome of 1000 subjects for ten common human disorders at the sequence level; d) the evaluation of the phenotypic consequences of structural and sequence changes of the human genome; and e) the integration of computational biology data of medical conditions for prevention, diagnosis, treatment of common human diseases. The programme will bring together academic, pharmaceutical and biotech stakeholders fostering the development and implementation of genomic medicine at the individual and collective levels.