title: Whole genome prediction for preimplantation genetic diagnosis.
abstract: BACKGROUND
  Preimplantation genetic diagnosis (PGD) enables profiling of embryos for genetic disorders prior to implantation. The majority of PGD testing is restricted in the scope of variants assayed or by the availability of extended family members. While recent advances in single cell sequencing show promise, they remain limited by bias in DNA amplification and the rapid turnaround time (<36 h) required for fresh embryo transfer. Here, we describe and validate a method for inferring the inherited whole genome sequence of an embryo for preimplantation genetic diagnosis (PGD).
  
  
  METHODS
  We combine haplotype-resolved, parental genome sequencing with rapid embryo genotyping to predict the whole genome sequence of a day-5 human embryo in a couple at risk of transmitting alpha-thalassemia.
  
  
  RESULTS
  Inheritance was predicted at approximately 3 million paternally and/or maternally heterozygous sites with greater than 99% accuracy. Furthermore, we successfully phase and predict the transmission of an HBA1/HBA2 deletion from each parent.
  
  
  CONCLUSIONS
  Our results suggest that preimplantation whole genome prediction may facilitate the comprehensive diagnosis of diseases with a known genetic basis in embryos.
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195 USA.
authors.forename: Akash
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Natera Inc, San Carlos, CA 94070 USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Ryan
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195 USA.
authors.forename: Jacob O
authors.initials: JO
authors.lastname: Kitzman
authors.affiliation: Natera Inc, San Carlos, CA 94070 USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Wemmer
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195 USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Snyder
authors.affiliation: Natera Inc, San Carlos, CA 94070 USA.
authors.forename: Styrmir
authors.initials: S
authors.lastname: Sigurjonsson
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195 USA.
authors.forename: Choli
authors.initials: C
authors.lastname: Lee
authors.affiliation: Natera Inc, San Carlos, CA 94070 USA.
authors.forename: Milena
authors.initials: M
authors.lastname: Banjevic
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195 USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Zarutskie
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195 USA.
authors.forename: Alexandra P
authors.initials: AP
authors.lastname: Lewis
authors.affiliation: Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195 USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Shendure
authors.affiliation: Natera Inc, San Carlos, CA 94070 USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Rabinowitz