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Sequencing of genomes has led to the discovery of a spectrum of both small-scale and large-scale genetic variation among individuals. Changes in copy-number and genome structural variation are common in most mammalian species and affect a wide range of phenotypic traits. The goal of this symposium will be to explore the relative impact of structural variation to common and rare human genetic diseases; discuss our understanding of ‘normal’ patterns of structural variation and its origin based on examining additional human genomes using new sequencing technologies; explore the extent of intraspecific variation in other organisms and their importance in phenotypic traits; and discuss the adaptive importance of this form of variation during the evolution of mammalian species.