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Familial haplotyping and embryo analysis for Preimplantation Genetic Diagnosis (PGD) using DNA microarrays: a proof of principle study



Development of PGD assays for molecular disorders is based on analysis of a familial mutation together with linked polymorphic STR markers; a process which is lengthy and requires the identification of multiple informative markers prior to PGD analysis. On the other hand, whole genome amplification (WGA), in conjunction with microarray platforms, allows the use of a universal assay for the analysis of a very large number of SNP markers at once. The aim of this study was to test high throughput pre-PGD familial haplotyping for in-case blastomere analysis in order to eliminate time-consuming pre-case preparations for each family.


A PGD cycle was performed for a couple with paternal Charcot Marie Tooth 1A (CMT1A) using a classic multiplex nested PCR approach. Mutant embryos from the case were blindly reanalyzed, as single or multi-cell biopsies, using a multiple displacement amplification-based WGA protocol and microarray SNP analysis. In parallel, relevant genomic DNA samples from the family were also analyzed by SNP microarray.


After applying a ‘unique informative allele’ selection algorithm to the data, this array-based assay reconfirmed the initial diagnosis in all samples.


We describe a PGD method that is both accurate and feasible during the time-frame required for embryo transfer. This strategy greatly reduces the time for pre-case haplotype preparation.

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We thank Rabbi David and Mrs. Anita Fuld for their generous and ongoing support.

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The authors declare that they have no conflict of interest.

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Correspondence to G. Altarescu.

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Capsule The classic STR-based method for PGD of monogenic disorders requires time consuming pre-case preparations. In this proof of principle investigation, we describe a SNP microarray-based methodology that accomplishes pre-PGD case preparations in a fraction of the time without compromising on diagnostic accuracy.

G. Altarescu and D. A. Zeevi are equal contributing authors

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Altarescu, G., Zeevi, D.A., Zeligson, S. et al. Familial haplotyping and embryo analysis for Preimplantation Genetic Diagnosis (PGD) using DNA microarrays: a proof of principle study. J Assist Reprod Genet 30, 1595–1603 (2013).

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  • Preimplantation genetic diagnosis
  • SNP microarray
  • Single cell
  • Haplotyping
  • Whole genome amplification