Genomes evolve with both mutations and large scale events, such as inversions, translocations, duplications and losses, that modify the structure of a set of chromosomes. In order to study these types of large-scale events, the first task is to select, in different genomes, sub-sequences that are considered “equivalent”. Many approaches have been used to identify equivalent sequences, either based on biological experiments, gene annotations, or sequence alignments. These techniques suffer from a variety of drawbacks that often result in the impossibility, for independent researchers, to reproduce the datasets used in the studies, or to adapt them to newly sequenced genomes. In this paper, we show that carefully selected small probes can be efficiently used to construct datasets. Once a set of probes is identified – and published –, datasets for whole genome comparisons can be produced, and reproduced, with elementary algorithms; decisions about what is considered an occurrence of a probe in a genome can be criticized and reevaluated; and the structure of a newly sequenced genome can be obtained rapidly, without the need of gene annotations or intensive computations.