EGAGenomicsIllumina HiSeq 2000;https://ega-archive.org/datasets/EGAD000010022573EGA dataset EGAD00001002257EGA<h4>Background</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Our results suggest that preimplantation whole genome prediction may facilitate the comprehensive diagnosis of diseases with a known genetic basis in embryos.Whole genome prediction for preimplantation genetic diagnosis.Kumar Akash A, Ryan Allison A, Kitzman Jacob O JO, Wemmer Nina N, Snyder Matthew W MW, Sigurjonsson Styrmir S, Lee Choli C, Banjevic Milena M, Zarutskie Paul W PW, Lewis Alexandra P AP, Shendure Jay J, Rabinowitz Matthew MVasp, VASP, Data Set., DmelCG15112, ENHANCER OF ATNSI ACTIVITY, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, ENA/VASPNewborn Infants, Neonates, NEWBORN (0-27 DAYS), Neonatal, study, Industrial, Pan-genome, Industrial Arts, Data Set, Infants, Genomes, Core Genome, read., Arts, Newborns, Accessory Genome, sequence, Newborn Infant, Newborn, Neonate, whole genome, Father, Pangenome, primary structure of sequence macromoleculeDiagnoses and Examination, Antemortem Diagnoses, screening, Postmortem Diagnoses, Antemortem Diagnosis, findings, familial, signs, whole genome, Diagnoses and Examinations, Diagnosis, Examination and Diagnoses, Diagnoses, genetic, Postmortem, Screenings, Mass Screenings, Examinations and Diagnoses, Mass, symptoms, Screening, inherited genetic, Antemortem, Diagnoses., Postmortem Diagnosis, constitutitional genetic, hereditary, DiagnoseNetworks, Scientific Bias, Antemortem Diagnosis, Prenatal Structures, Disorders, Inheritance, Extended, Kinship, Approximate, PHGDHD, plant germ, Suggestion, Greater Than, EMBRYO, Fresh Specimen, Thalassemia-alpha, Diagnosis, Long Term, A10, Status, Relative, Techniques, Single-Gene, SERA, PRIOR, A-THAL, Prior Medication Usage, sequencing assay, diseases, Method, Epidemiologic Biase, symptoms, Life Cycle, Embryologic, diseases and disorders, Ecological, Prior, Transfer, Effect, alpha-Thalassemias, Family Life Cycle, Ecological Biases, human disease, heterozygous genotype, Kinship Network, Genomes, Implantation Method of Administration, availability, Defects, NLS, A-thalassemia, 4930479N23, procedures, NLS1, Defect, Thalassemia alpha, hba2, Fast, genetic, CD31, Single-Gene Defect, Methodological Studies, Statistical Biases, Familiar, Rapid, Ecological Bias, Homo sapiens disease, Systematic, Family Life Cycles, Epidemiologic Biases, Heterozygote, Long-Term Effects, Tubal Embryo Transfer, And/Or, Comprehensive, Diagnose, PGAD, Presumptive, screening, Pre, Constraint, Hba, sequencing_assay, HBAM, Scientific, embryo, Genetic Disorders, Step Parents, Epidemiologic, HBH, familial, Longterm Effect, MT (more than), Limitation, PARENT, Ecological Fallacies, developing organism, Resolution of Pathologic Process, Hba-a1, Procedure, alpha-Thalassemia, Hba-a2, Stepparent, Haplotype, results, PGDH, predicted, Diagnoses, Outcome Measurement Errors, Parenthood, Experimental, Postmortem, Screenings, Tubal Embryo Stage Transfer, Hba1, Examinations and Diagnoses, Relative Risks, Alpha thalassaemia, Diseases, About, Step-Parents, Inborn Genetic Disease, NOS, Administration via Implantation, Genetic Disorder, Truncation Bias, Postmortem Diagnosis, Filiation, Inborn, Diagnoses and Examination, Postmortem Diagnoses, Parent, Bias, Rapidly, Risk, Nucleic Acid Sequencing, prior_drugs, Parental Age, SPCPJ732.04c, PDG, signs, Parental Ages, Coupled, Methodological, whole genome, Based., Outcome Measurement, Hemoglobin H, Methodological Study, Prenatal Structure, A-Thalassemia, Million, Age, Leading, Requisite, Experimental Bias, Life Cycles, Genetic Diseases, Outcome Measurement Error, disease, 10E6, Thalassemia, Hereditary, GT, Extension, inherited genetic, Scope, Alpha, Sequence Analysis, Pathology Resolution, Single-Gene Defects, Fresh, Resolved License, other disease, Restricted, Family Member, Procedures, Effects, Ecological Fallacy, FRESH, Truncation, Prenatal, Systematic Bias, Hereditary Diseases, Network, alpha-thalassemia trait, Hbat1, method, SEQUENCING, Blastocyst Transfer, Biopolymer Sequencing, Alpha Thalassemia, Embryo Transfers, PGD, method used in an experiment, 6PGD, Heterozygosity, Sites, Mass, Studies, Screening, Requirement, disease or disorder, million, Parenthood Status, Antemortem, Technique, Stepparents, Fallacies, Site, Couple, Genetic, Pathologic Process Resolution, Research, Longterm, Suggest, Inborn Genetic, Aggregation, Diagnoses and Examinations, Long-Term, Coupling, Structure, Sequencing, Solution, α-thalassemia, non-neoplastic, Study, embryonic organism, Implantation, Ages, Disorder, Presumptive Structure, Resolve, Embryonic Structure, Physiologic Resolution, disorder, Long-Term Effect, Approximately, Kinship Networks, Known, constitutitional genetic, Family, Single Gene Defects, Biase, HEL-S-113, Antemortem Diagnoses, Fallacy, Disease, Molecular Biology, Human Embryo, Genetic Disease, findings, Family Research, Heterozygous, More Than, Preceding, Parental, disorders, Truncation Biases, medical condition, 3PGDH, Resolved, Examination and Diagnoses, Testing, Family Members, Implant, MT, One Million, Mass Screenings, Embryos, Long Term Effects, Errors, sequence, Step-Parent, condition, 3-PGDH, prior drugs, Extend, background, techniques, alpha thalassemia, Relative Risk, Mandatory, Resolution, Before, Embryonic, Basic, Embryo, 1000000, Risks, Basis, Biases, Required, primary structure of sequence macromolecule, introduction, Longterm Effects, NUCLEIC ACID SEQUENCING, Presumptive Structures, plan specification, 10^6, Hemoglobin H Disease, Hereditary Disease, developmental tissue, Error, Aggregation Bias, DEL, Families, Inborn Genetic Diseases, Statistical Bias, GRO:0005343, Restriction, BEFORE, Statistical, Transfers, HBA-T3, HBA-T2, hereditary, Relatives, methodologyfalseena-DATASET-EMSEQ-23-07-2016-16:45:57:226-24 - samplesThis dataset includes whole genome sequence information for three individuals (Mother, Father and Newborn) used in this study. Genomes were sequenced using Illumina HiSeq technology. Files included are fastq files in paired read format.2017-07-26 15:39:29EGAD00001002257960626019723EGAC00001000265EGAS00001001020