Validation of concurrent preimplantation genetic testing for polygenic and monogenic disorders, structural rearrangements, and whole and segmental chromosome aneuploidy with a single universal platform.

Preimplantation genetic testing (PGT) has been successfully applied to reduce the risk of miscarriage, improve IVF success rates, and prevent inheritance of monogenic disease and unbalanced translocations. The present study provides the first method capable of simultaneous testing of aneuploidy (PGT-A), structural rearrangements (PGT-SR), and monogenic (PGT-M) disorders using a single platform. Using positive controls to establish performance characteristics, accuracies of 97 to >99% for each type of testing were observed. In addition, this study expands PGT to include predicting the risk of polygenic disorders (PGT-P) for the first time. Performance was established for two common diseases, hypothyroidism and type 1 diabetes, based upon availability of positive control samples from commercially available repositories. Data from the UK Biobank, eMERGE, and T1DBASE were used to establish and validate SNP-based predictors of each disease (7,311 SNPs for hypothyroidism and 82 for type 1 diabetes). Area under the curve of disease status prediction from genotypes alone were 0.71 for hypothyroidism and 0.68 for type 1 diabetes. The availability of expanded PGT to evaluate the risk of polygenic disorders in the preimplantation embryo has the potential to lower the prevalence of common genetic disease in humans.

Applying targeted next generation sequencing to dried blood spot specimens from suspicious cases identified by tandem mass spectrometry-based newborn screening.

BACKGROUND: Tandem mass spectrometry (TMS)-based newborn screening has been proven successful as one of the public healthcare programs, although the practicability has not yet been specifically addressed. METHODS: Sixty residual dried blood spot (DBS) specimens from confirmation/diagnosis-insufficient cases discovered by TMS screening were analyzed by targeted next generation sequencing (TNGS) assay. RESULTS: In total, 26, 11, 9, and 14 cases were diagnosed as positive, high risk, low risk, and negative, respectively. CONCLUSIONS: Applying the DBS-based TNGS assay for the accurate and rapid diagnosis of inborn errors of metabolism (IEMs) is feasible, competent, and advantageous, enabling a simplified TMS screening-based, TNGS assay-integrated newborn screening scheme highlighting an efficient, executable, and one-step screening-to-diagnosis workflow.