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Background  F REGENE  simulates sequence-level data over large genomic regions in large populations. Because, unlike coalescent simulators, it works forwards through time, it allows complex scenarios of selection, demography, and recombination to be modelled simultaneously. Detailed tracking of sites under selection is implemented in F REGENE  and provides the opportunity to test theoretical predictions and gain new insights into mechanisms of selection. We describe here main functionalities of both F REGENE  and S AMPLE , a companion program that can replicate association study datasets.    Results  We report detailed analyses of six large simulated datasets that we have made publicly available. Three demographic scenarios are modelled: one panmictic, one substructured with migration, and one complex scenario that mimics the principle features of genetic variation in major worldwide human populations. For each scenario there is one neutral simulation, and one with a complex pattern of selection.    Conclusion  F REGENE  and the simulated datasets will be valuable for assessing the validity of models for selection, demography and population genetic parameters, as well as the efficacy of association studies. Its principle advantages are modelling flexibility and computational efficiency. It is open source and object-oriented. As such, it can be customised and the range of models extended.

Fregene: Simulation of realistic sequence-level data in populations and ascertained samples