SNP array-based copy number and genotype analyses for preimplantation genetic diagnosis of human unbalanced translocations

Chris M. J. van Uum, Servi J. C. Stevens*, Joseph C. F. M. Dreesen, Marion Drusedau, Hubert J. Smeets, Bertien Hollanders-Crombach, Christine E. M. de Die-Smulders, Joep P. M. Geraedts, John J. M. Engelen, Edith Coonen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Web of Science)


Preimplantation genetic diagnosis (PGD) for chromosomal rearrangements (CR) is mainly based on fluorescence in situ hybridisation (FISH). Application of this technique is limited by the number of available fluorochromes, the extensive preclinical work-up and technical and interpretative artefacts. We aimed to develop a universal, off-the-shelf protocol for PGD by combining single-nucleotide polymorphism (SNP) array-derived copy number (CN) determination and genotyping for detection of unbalanced translocations in cleavage-stage embryos. A total of 36 cleavage-stage embryos that were diagnosed as unbalanced by initial PGD FISH analysis were dissociated (n=146) and amplified by multiple displacement amplification (MDA). SNP CNs and genotypes were determined using SNP array. Epstein-Barr Virus-transformed cell lines with known CR were used for optimising the genomic smoothing (GS) length setting to increase signal to noise ratio. SNP CN analysis showed 23 embryos (64%) that were unbalanced in all blastomeres for the chromosomes involved in the translocation, 5 embryos (14%) that were normal or balanced in all blastomeres and 8 embryos (22%) that were mosaic. SNP genotyping, based on analysis of informative SNP loci with opposing homozygous parental genotypes, confirmed partial monosomies associated with inheritance of unbalanced translocation in surplus embryos. We have developed a universal MDA-SNP array technique for chromosome CN analysis in single blastomeres. SNP genotyping could confirm partial monosomies. This combination of techniques showed improved diagnostic specificity compared with FISH and may provide more reliable PGD analysis associated with higher embryo transfer rate. European Journal of Human Genetics (2012) 20, 938-944; doi:10.1038/ejhg.2012.27; published online 29 February 2012
Original languageEnglish
Pages (from-to)938-944
JournalEuropean Journal of Human Genetics
Issue number9
Publication statusPublished - Sept 2012


  • preimplantation genetic diagnosis
  • SNP array
  • chromosomal translocations
  • whole-genome amplification
  • genotyping
  • blastomeres

Cite this