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Open AccessArticle

Next Generation Sequencing in Newborn Screening in the United Kingdom National Health Service

1
Sheffield Diagnostic Genetics Service (SDGS), Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield S10 2TH, UK
2
Division of Pharmacy, Diagnostics and Genetics, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield S10 2TH, UK
3
Department of Infection, Immunity & Cardiovascular Disease, Faculty of Medicine, Dentistry & Health University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
4
University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK
9
‖Present address: Sheffield Bioinformatics Core, Sheffield Biomedical Research Centre, The University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Present address: Genetics Centre, Guy’s Hospital, Great Maze Pond, London SE1 9RT, UK.
§
Present address: Pathology Department, Sidra Medicine, Main Hospital, H2M-24091, PO Box 26999, Doha, Qatar.
Int. J. Neonatal Screen. 2019, 5(4), 40; https://doi.org/10.3390/ijns5040040
Received: 1 August 2019 / Revised: 14 October 2019 / Accepted: 24 October 2019 / Published: 5 November 2019
Next generation DNA sequencing (NGS) has the potential to improve the diagnostic and prognostic utility of newborn screening programmes. This study assesses the feasibility of automating NGS on dried blood spot (DBS) DNA in a United Kingdom National Health Service (UK NHS) laboratory. An NGS panel targeting the entire coding sequence of five genes relevant to disorders currently screened for in newborns in the UK was validated on DBS DNA. An automated process for DNA extraction, NGS and bioinformatics analysis was developed. The process was tested on DBS to determine feasibility, turnaround time and cost. The analytical sensitivity of the assay was 100% and analytical specificity was 99.96%, with a mean 99.5% concordance of variant calls between DBS and venous blood samples in regions with ≥30× coverage (96.8% across all regions; all variant calls were single nucleotide variants (SNVs), with indel performance not assessed). The pipeline enabled processing of up to 1000 samples a week with a turnaround time of four days from receipt of sample to reporting. This study concluded that it is feasible to automate targeted NGS on routine DBS samples in a UK NHS laboratory setting, but it may not currently be cost effective as a first line test.
Keywords: newborn screening; next generation sequencing; automation newborn screening; next generation sequencing; automation
MDPI and ACS Style

van Campen, J.C.; Sollars, E.S.A.; Thomas, R.C.; Bartlett, C.M.; Milano, A.; Parker, M.D.; Dawe, J.; Winship, P.R.; Peck, G.; Grafham, D.; Kirk, R.J.; Bonham, J.R.; Goodeve, A.C.; Dalton, A. Next Generation Sequencing in Newborn Screening in the United Kingdom National Health Service. Int. J. Neonatal Screen. 2019, 5, 40.

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