Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro

Senthilkumar A. Natesan, Alex J. Bladon, Serdar Coskun, Wafa Qubbaj, Renata Prates, Santiago Munne, Edith Coonen, Joseph C. F. M. Dreesen, Servi J. C. Stevens, Aimee D. C. Paulussen, Sharyn E. Stock-Myer, Leeanda J. Wilton, Souraya Jaroudi, Dagan Wells, Anthony P. C. Brown, Alan H. Handyside*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Purpose: Our aim was to compare the accuracy of family- or digease-specific targeted haplotyping and direct-mutation-detection strategies with the accuracy of genome-wide mapping of the parental origin of each chromosome, or karyomapping, by single-nudeotide polymorphism genotyping of the parents, a dose relative of known disease status, and the embryo cell(s) used for preimplantation genetic diagnosis of single-gene-defects in. a single cell or small numbers of cells biopsied from human embryos following in vitro fertilization. Methods: Genomic DNA and whole-genome amplification products from. embryo samples, which were previously diagnosed by targeted haplotyping, were genotyped for single-nucleotide polymor phisms genome-wide detection and retrospectively analyzed blind by karyomapping. Results: Single-nucleotide polymorphism genotyping and karyomapping were successful in 213/218 (97.7%) samples from 44 preimplantation genetic diagnosis cycles for 25 single-gene defects with various modes of inheritance distributed widely across the genome. Karyomapping was concordant with targeted haplotyping in 208 (97.7%) samples, and the five nonconcordant samples were all in consanguineous regions with limited or inconsistent haplotyping results. Conclusion: Genome-wide karyomapping is highly accurate and facilitates analysis of the inheritance of almost any single-gene defect, or any combination of loci, at the single-cell level, greatly expanding the range of conditions for which preimplantation genetic diagnosis can be offered Clinically without the need for customized test development.
Original languageEnglish
Pages (from-to)838-845
JournalGenetics in Medicine
Issue number11
Publication statusPublished - Nov 2014


  • karyomapping
  • preimplantation genetic diagnosis
  • single-gene defect
  • single-nucleotide polymorphism
  • whole-genome amplification

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