Expanded clinical validation of Haploseek for comprehensive preimplantation genetic testing

David A. Zeevi*, Daniel Backenroth, Elinor Hakam-Spector, Paul Renbaum, Tzvia Mann, Fouad Zahdeh, Reeval Segel, Sharon Zeligson, Talia Eldar-Geva, Ido Ben-Ami, Adi Ben-Yehuda, Shai Carmi, Gheona Altarescu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Purpose: We previously developed Haploseek, a method for comprehensive preimplantation genetic testing (PGT). However, some key features were missing, and the method has not yet been systematically validated. Methods: We extended Haploseek to incorporate DNA from embryo grandparents and to allow testing of variants on chromosome X or in regions where parents share common haplotypes. We then validated Haploseek on 151 embryo biopsies from 27 clinical PGT cases. We sequenced all biopsies to low coverage (0.2×), and performed single-nucleotide polymorphism (SNP) microarray genotyping on the embryos’ parents and siblings/grandparents. We used the extended Haploseek to predict chromosome copy-number variants (CNVs) and relevant variant-flanking haplotypes in each embryo. We validated haplotype predictions for each clinical sample against polymerase chain reaction (PCR)-based PGT case results, and CNV predictions against established commercial kits. Results: For each of the 151 embryo biopsies, all Haploseek-derived haplotypes and CNVs were concordant with clinical PGT results. The cases included 17 autosomal dominant, 5 autosomal recessive, and 3 X-linked monogenic disorders. In addition, we evaluated 1 Robertsonian and 2 reciprocal translocations, and 17 cases of chromosome copy-number counting were performed. Conclusion: Our results demonstrate that Haploseek is clinically accurate and fit for all standard clinical PGT applications.

Original languageAmerican English
Pages (from-to)1334-1340
Number of pages7
JournalGenetics in Medicine
Issue number7
StatePublished - Jul 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.


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