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

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.