Whole-genome analysis of a putative rare and complex interchromosomal reciprocal insertion: thorough investigations for a straightforward interpretation

Published:November 29, 2021DOI:


      Research question

      Should whole-genome investigations be considered systematically before a complex chromosomal abnormality preimplantation genetic testing for structural chromosomal rearrangements (PGT-SR) management is carried out using conventional cytogenetic techniques?


      A male carrying a putative rare interchromosomal reciprocal insertion (IRI) 46,XY,ins(14;?)(q11;?).ish der(14)ins(14;22)(q11.2;q11.2q11.2)(xcp14+,xcp22+,N25+,3’TRA/D+),der(22)ins(22;14)(q11.2;q11.2q11.2)(xcp22+,xcp14+,N25-,5’TRA/D+), and his partner were referred to our centre for preimplantation genetic testing analysis after three spontaneous miscarriages. Whole-genome sequencing was used to distinguish between the proposed IRI and an alternative explanation of reciprocal translocation. Fluorescence in-situ hybridization was used to detect all chromosome segments involved in this chromosomal rearrangement, to identify transferable normal and balanced embryos.


      Whole-genome sequencing allowed the determination of the number of chromosomal breakpoints involved in chromosomal rearrangement between chromosomes 14 and 22. Finally, only two breakpoints were identified instead of four in IRI rearrangements, which suggests a reciprocal translocation rearrangement. A probe strategy was established to highlight all chromosomal imbalances, whether IRI or reciprocal translocation, and preimplantation genetic testing cycles were achieved.


      Conventional cytogenetic techniques are not capable of identifying all complex chromosomal rearrangements, especially those involving centromeric regions and short arms of acrocentric chromosomes. The advent of new sequencing technologies has allowed for a better appreciation of genome complexity. In this study, whole-genome analysis provided additional information to explain the occurrence of genomic events and confirmed that the initial diagnosis of IRI identified by conventional cytogenetic techniques was, in fact, a simple reciprocal translocation. A reliable PGT-SR strategy was proposed for this couple to achieve their parental project.


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      Reda Zenagui, PhD, is a graduate in molecular genetics from Montpellier University, France. He currently works at the Preimplantation Genetic Testing (PGT) unit at Montpellier Hospital. His research focus is on improving reproductive care in patients with chromosomal abnormalities.
      Key message
      Whole-genome investigations of a putative interchromosomal reciprocal insertion by paired-end sequencing technologies have been beneficial for chromosomal rearrangement identification as a reciprocal translocation and genetic counselling improvement technique. These investigations have provided a targeted preimplantation genetic testing of structural rearrangement (PGT-SR) strategy to avoid embryonic risks related to unbalanced chromosomes.