title: Genome-wide karyomapping accurately identifies the inheritance of single-gene defects in human preimplantation embryos in vitro.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Illumina, Cambridge, UK.
authors.forename: Senthilkumar A
authors.initials: SA
authors.lastname: Natesan
authors.affiliation: Illumina, Cambridge, UK.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Bladon
authors.affiliation: Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Serdar
authors.initials: S
authors.lastname: Coskun
authors.affiliation: Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Wafa
authors.initials: W
authors.lastname: Qubbaj
authors.affiliation: Reprogenetics, Livingston, New Jersey, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Prates
authors.affiliation: Reprogenetics, Livingston, New Jersey, USA.
authors.forename: Santiago
authors.initials: S
authors.lastname: Munne
authors.affiliation: 1] Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, Maastricht, The Netherlands [2] GROW, School for Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Edith
authors.initials: E
authors.lastname: Coonen
authors.affiliation: 1] GROW, School for Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands [2] Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Joseph C F M
authors.initials: JC
authors.lastname: Dreesen
authors.affiliation: 1] GROW, School for Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands [2] Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Servi J C
authors.initials: SJ
authors.lastname: Stevens
authors.affiliation: 1] GROW, School for Oncology and Developmental Biology, University of Maastricht, Maastricht, The Netherlands [2] Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Aimee D C
authors.initials: AD
authors.lastname: Paulussen
authors.affiliation: Preimplantation Genetics, Melbourne IVF, East Melbourne, Victoria, Australia.
authors.forename: Sharyn E
authors.initials: SE
authors.lastname: Stock-Myer
authors.affiliation: Preimplantation Genetics, Melbourne IVF, East Melbourne, Victoria, Australia.
authors.forename: Leeanda J
authors.initials: LJ
authors.lastname: Wilton
authors.affiliation: Reprogenetics UK, Institute of Reproductive Sciences, Oxford, UK.
authors.forename: Souraya
authors.initials: S
authors.lastname: Jaroudi
authors.affiliation: Reprogenetics UK, Institute of Reproductive Sciences, Oxford, UK.
authors.forename: Dagan
authors.initials: D
authors.lastname: Wells
authors.affiliation: Illumina, Cambridge, UK.
authors.forename: Anthony P C
authors.initials: AP
authors.lastname: Brown
authors.affiliation: 1] Illumina, Cambridge, UK [2] The Bridge Centre, London, UK.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Handyside
mesh_terms: D001755:Blastocyst; D002874:Chromosome Mapping / Q000379:methods*; D005260:Female; D015894:Genome, Human; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D007621:Karyotyping / Q000379:methods*; D008297:Male; D010290:Parents; D020641:Polymorphism, Single Nucleotide; D019836:Preimplantation Diagnosis / Q000379:methods*; D015203:Reproducibility of Results; D012189:Retrospective Studies