1. Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro.
- Author
-
Natesan SA, Bladon AJ, Coskun S, Qubbaj W, Prates R, Munne S, Coonen E, Dreesen JC, Stevens SJ, Paulussen AD, Stock-Myer SE, Wilton LJ, Jaroudi S, Wells D, Brown AP, and Handyside AH
- Subjects
- Blastocyst, Female, Genome, Human, Humans, In Vitro Techniques, Male, Parents, Polymorphism, Single Nucleotide, Reproducibility of Results, Retrospective Studies, Chromosome Mapping methods, Genotyping Techniques methods, Karyotyping methods, Preimplantation Diagnosis methods
- Abstract
Purpose: Our aim was to compare the accuracy of family- or disease-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-nucleotide polymorphism genotyping of the parents, a close 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 polymorphisms 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.
- Published
- 2014
- Full Text
- View/download PDF