A new approach for detecting chromosomal inversions, based on the rece
ntly developed technique of chromosome orientation and direction fluor
escence in situ hybridization (GOD-FISH), is presented. GOD-FISH is a
strand-specific modification of standard FISH technology which allows
the hybridization of single-stranded probes to one, and only one, chro
matid of a metaphase chromosome. It can be used to determine the absol
ute 5'-to-3' direction of DNA target sequences with respect to the sho
rt-to-long arm direction of a given chromosome. Since an inversion rev
erses the orientation of DNA sequences within the inverted region, an
inversion becomes detectable as a ''switch'' in probe signal from one
chromatid to the other, when compared to a reference probe outside of
the inverted region. Pericentric inversions in chromosomes 1, 8, 10, a
nd X, which had previously been identified by chromosome banding, were
analyzed by the GOD-FISH technique. The results presented here demons
trate that GOD-FISH can be used for the detection of pericentric inver
sions and that, in some instances, it provides additional information
not obtainable by more conventional methods of cytogenetic analysis. P
ractical limitations of the GOD-FISH technique are also discussed.