Studies of metaphase and interphase chromosomes using fluorescence in situ hybridization.

Our measurements have bearing on the resolution with which maps can be constructed and abnormalities can be detected by studying the proximity of DNA sequences in metaphase and interphase chromosomes. The results of our analyses are summarized in Figure 8. Metaphase chromosomes are compacted sufficiently that it is impractical to order sequences separated by less than approximately 1 Mbp. In contrast, 100-kbp resolution can be obtained in interphase chromosomes. Distance measurements reveal that interphase chromatin behaves as a random polymer over distances up to 1-2 Mbp. At greater distances, higher order constraints, perhaps the dimensions of the individual chromosome domains, come into play. A caveat remains: Because the effect of the FISH procedure on native chromosome organization is not well understood, these conclusions may not be applicable to native chromatin. We have illustrated that FISH, with appropriately chosen probes, can supplement conventional cytogenetics in the study of chromosome abnormalities. The technique is increasingly being applied in research laboratories to detect and characterize chromosome abnormalities and point the way to the location of genes involved in human disease.