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Systems genetics is the extension of genetics to the system-level. It aims at understanding the relationship between genotypes and molecular phenotpes at the genome-scale, thus integrating genomics with large-scale molecular and phenotypic profiling. This opens the door to the investigating of the genetic basis of complex traits in a variety of model systems, from yeast growth phenotype to human disease. Taking advantage of natural genetic variation allows to investigate the effect of many mild genetic perturbations, an approach which contrasts with the all-or-none targeted genetic perturbations.