Molecular Cytogenetic Characterization of Rare but Repeatedly Observed Inversions in German Population.

Introduction: The term inversion refers to an aberration caused by two breakage and fusion events found in one or both arms of a chromosome. The presence of such aberrations can but must not be associated with infertility or unbalanced products of conception. Normally, inversions are not associated with phenotypic alterations for the carrier. Despite the fact that most such inversions are de novo and unique, recurrent breakpoints have also been reported.

Methods: Here two recurrent paracentric inversions in the long arm of chromosomes 11 and 12 and a pericentric one in chromosome 10 were studied in at least 10 unrelated (infertile) patients, each. Breakpoints were narrowed down by fluorescence in situ hybridization applying locus-specific bacterial artificial chromosome-derived probes.

Results: Molecular cytogenetically identical breakpoints could be characterized for all three studied inversions. Pericentric inversion inv(10)(p11.21q21.2), previously reported to be of single origin and distributed mainly in Northern Europe, could be found to be present all over Germany, too. In the studied cases with paracentric inversion inv(11)(q21q23.3), recurrent breakpoints were found in all parts of Germany, as well; however, additional 2 cases with slightly different breakpoints were characterized besides. Most interestingly, inversion inv(12)(q14.1∼14.2q24.11∼24.13) had always the same recurrent breakpoints and presented an exclusive occurrence in North-Western part of Germany.

Conclusion: Overall, (at least) three different cytogenetically detectable recurrent inversions were characterized here. This highlights that such events may be more frequent in human population than yet suggested. Accordingly, such events might even spread in (middle European) human population. Specific impact on reproduction and fitness of inversion carriers characterized here seems to be negligible. Nonetheless, such recurrent rearrangements need more attention as they may provide valuable information for genetic counseling in future.