Preimplantation genetic testing using Karyomapping for a paternally inherited reciprocal translocation: a case study

  • C. E. BeyerEmail author
  • A. Lewis
  • E. Willats
  • J. Mullen



Preimplantation genetic testing (PGT) using Karyomapping is used to screen embryos for single gene disorders prior to implantation. While Karyomapping is not designed to screen for abnormalities in chromosome copy number, this testing is based upon a genome-wide analysis of single nucleotide polymorphisms (SNP) and, as such, some chromosome abnormalities are detected. The aim of this study was to validate whether Karyomapping could provide reliable and accurate PGT for a paternal 46,XY,t(10;19)(p15;p13.3) reciprocal translocation.


Feasibility/validation for PGT was performed using DNA from the couple, as well as DNA from the paternal parents and from a previous unbalanced pregnancy. Karyomapping was performed using Illumina’s HumanKaryomap-12 BeadChip microarray technology. SNP analysis was performed using BlueFuse Multi software (Illumina). Transmission of the translocation was assessed through the analysis of SNP markers on the chromosome regions of interest.


PGT-SR was determined to be feasible as chromosomal SNP analysis could reliably distinguish normal/balanced outcomes from all unbalanced outcomes. The couple transferred a normal/balanced embryo in an elective single embryo transfer procedure following 2 IVF/PGT-SR cycles. A clinical pregnancy was achieved.


This is the first report of PGT-SR test validation using Karyomapping for a 46,XY,t(10;19)(p15;p13.3) reciprocal translocation. Karyomapping may offer a means of detecting unbalanced forms of chromosome rearrangements when other PGT platforms fail.


Preimplantation genetic diagnosis Preimplantation genetic testing Chromosome rearrangement Phasing Karyomapping 



The authors would like to thank all the staff at Monash IVF clinic for referring and coordinating the couple and the genetics staff at Monash IVF for their genetic analysis and contributions towards this paper.

Authors’ roles

Claire E Beyer—case study concept and design, data acquisition, study execution, analysis, manuscript drafting, interpretation of data.

Amy Lewis—data acquisition, study execution, analysis, manuscript drafting, interpretation of data.

Elissa Willats—Manuscript drafting, interpretation of data.

Jayne Mullen—Manuscript review.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Katz MG, Fitzgerald L, Bankie A, Savulescu J, Cram DS. Issues and concerns of couples presenting for preimplantation genetic diagnosis (PGD). Prenat Diagn. 2002;22:1117–22.CrossRefGoogle Scholar
  2. 2.
    Handyside AH, Harton GL, Mariani B, Thornhill AR, Affara N, Shaw MA, et al. Karyomapping: a universal method for genome wide analysis of genetic disease based on mapping crossovers between parental haplotypes. J Med Genet. 2010;47:651–8.CrossRefGoogle Scholar
  3. 3.
    Natesan S, Bladon A, Coskun S, Qubbaj W, Prates R, Munne S, et al. Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro. Genet Med. 2014;16:838–45.CrossRefGoogle Scholar
  4. 4.
    Griffin D, Gould R. What is Karyomapping and where does it fit in the world of preimplantation genetic diagnosis (PGD)? Med Res Arch. 2017;5(6):1–18.CrossRefGoogle Scholar
  5. 5.
    Cuman C, Beyer CE, Brodie D, Fullston T, Lin JI, Willats E, et al. Defining the limits of detection for chromosome rearrangements in the preimplantation embryo using next generation sequencing. Hum Reprod. 2018;33(8):1566–76.CrossRefGoogle Scholar
  6. 6.
    A technical guide to Karyomapping – phasing single gene defects. Illumina; 2015.Google Scholar
  7. 7.
    Infinium Karyomapping Assay Protocol Guide. 2015.Google Scholar
  8. 8.
    Kuliev A, Verlinsky O, Rechitsky S. Safety, accuracy and reproductive outcome of preimplantation genetic diagnosis. J IVF Reprod Med Genet. 2013;1:116.CrossRefGoogle Scholar
  9. 9.
    Natesan S, Handyside A, Thornhill C, Ottolini K, Sage M, Summers M, et al. Live birth after PGD with confirmation by a comprehensive approach (Karyomapping) for simultaneous detection of monogenic and chromosomal disorders. Reprod BioMed Online. 2014;29:600–5.CrossRefGoogle Scholar
  10. 10.
    Sarasa J, Wheeler K, Lansdowne L, Raberi A, Babariya D, Wells D. Clinical experience using single nucleotide polymorphism (SNP) arrays for preimplantation genetic diagnosis (PGD) of chromosomal translocations. Conferene paper P-658. Hum Reprod. 2015;30:403.Google Scholar
  11. 11.
    Giménez C, Sarasa J, Arjona C, Vilamajó E, Martínez-Pasarell O, Wheeler K, et al. Karyomapping allows preimplantation genetic diagnosis of a de-novo deletion undetectable using conventional PGD technology. Reprod BioMed Online. 2015;31(6):770–5.CrossRefGoogle Scholar
  12. 12.
    Stock-Myer S, Twomey A, Tang P, Kohfahl A, Martic M. PGD for reciprocal translocation and CNVs using Karyomapping. Australian Society of Diagnostic Genomics Abstract, 2017.Google Scholar
  13. 13.
    Colls P, Escudero T, Fischer J, Cekleniak NA, Ben-Ozer S, Meyer B, et al. Validation of array comparative genome hybridization for diagnosis of translocations in preimplantation human embryos. Reprod BioMed Online. 2012;24(6):621–9.CrossRefGoogle Scholar
  14. 14.
    Lai H, Chuang T, Wong L, Lee M, Hsieh C, Wang H, et al. Identification of mosaic and segmental aneuploidies by next-generation sequencing in preimplantation genetic screening can improve clinical outcomes compared to array-comparative genomic hybridization. Mol Cytogenet. 2017;10:14.CrossRefGoogle Scholar
  15. 15.
    Vera-Rodriguez M, Michel C, Mercader A, Bladon A, Rodrigo L, Kokocinski F, et al. Distribution patterns of segmental aneuploidies in human blastocysts identified by next-generation sequencing. Fertil Steril. 2016;105(4):1047–55.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Monash IVFClaytonAustralia

Personalised recommendations