Transmission electron microscopy of chromosomes by longitudinal section preparation: application to fragile X chromosome analysis.

We developed a method for the preparation of ultrathin longitudinal sections of chromosomes enabling TEM studies of whole chromosomes. By using a novel "repeat chill" method of exposing the glass slide and plastic block interface to liquid nitrogen, it was possible to separate consistently hardened epoxy resin-embedded chromosome spreads from glass slides for ultrathin longitudinal sectioning of entire spreads and of individual chromosomes. The method was applied to analyze the fragile X chromosome. The ultrastructure of centromeres, telomeres, fragile sites and other chromosomal areas can now be studied in detail.