The relationships between genetic or radiation hybrid (RH) and sequence maps of chromosome 22 have been reconsidered based on the sequence map. Integrated maps have been constructed by retaining only common markers between genetic or RH maps and the sequence map. Local inversions of markers have been detected. Ratios between either genetic or RH distances and sequence-based distances have been calculated for each map interval. Hot zones for recombination or radiation breakage have been delineated by merging together intervals displaying high distance ratios and located close to each other for sequence-constrained RH maps, and for female and male genetic maps. A statistically significant positive correlation was found between the distribution of disease-related genes and the hot zones for recombination or radiation breakage on both female genetic and Stanford-G3 RH maps. This observation indicates that investigation of chromosomal regions displaying inconsistencies between RH or genetic linkage and sequence-based maps can accelerate the initial phase of identification of disease-associated genes.