Fiber-fluorescence in situ hybridization analyses as a diagnostic application for orientation of microduplications

Abstract

Microduplications are normally invisible under microscopy and were not recognized before chromosomal microarray testing was available. Although it is difficult to confirm the orientation of duplicated segments by standard fluorescence in situ hybridization (FISH), our data indicates that fiber-FISH analysis has the potential to reveal the orientation of duplicated and triplicated segments of chromosomes. Recurrent microduplications reciprocal to microdeletions show tandem orientations of the duplicated segments, which is consistent with a non-allelic homologous recombination mechanism. Several random duplications showed tandem configurations and inverted duplications are rare. Further analysis is required to fully elucidate the basic mechanisms underlying such duplications/triplications.

Keywords: Chromosomal microarray testing, Copy number variation, Fiber-fluorescence in situ hybridization, Microduplication, Tandem orientation

Core tip: Fiber-fluorescence in situ hybridization analysis has the potential to reveal the orientation of duplicated and triplicated segments of chromosomes. Previously, we reported that interstitial duplications were aligned in tandem configurations, supporting the hypothesized mechanism of non-allelic homologous recombination; however, there were rare cases of inverted duplications. Further analysis is therefore required to fully elucidate the basic mechanisms underlying such duplications/triplications.