Challenges of using next generation sequencing in newborn screening

Reinstein, Eyal

doi:10.1017/s0016672315000178

Cited by 22 publications

(20 citation statements)

References 29 publications

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“…Here, we have demonstrated that it is technically feasible to perform targeted NGS on DBS DNA with a sufficiently high throughput and fast turnaround time that the assay could be used in a UK NBS pathway. To assess clinical sensitivity and specificity, the implementation of any targeted NGS assay for NBS should be carefully evaluated through pilot studies in the population to be screened [82,83]. This assessment was not an aim of our study.…”

Section: Discussionmentioning

confidence: 99%

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

Campen

Sollars

Thomas

et al. 2019

IJNS

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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.

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Section: Discussionmentioning

confidence: 99%

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

Campen

Sollars

Thomas

et al. 2019

IJNS

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“…Prenatal diagnosis contains features relating to the health of both the fetus and the parents [77]. Current methods including the combined test and invasive procedures (amniocentesis and chorionic villus sampling (CVS) used to screen the fetus for chromosomal abnormalities pose a risk to mother and fetus [78].…”

Section: Prenatal Diagnosismentioning

confidence: 99%

Strategies, Quality Control and Clinical Applications of Next Generation Sequencing

Khorshidi

Palangi

2018

Multidiscip Cancer Investig

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DNA sequencing is one of the great valuable techniques in molecular biology, which can be used to detect the sequence of nucleotides in a DNA fragment. The high-throughput sequencing known as Next Generation Sequencing (NGS) revolutionized genomic research and molecular biology; therefore, the whole human genome can be sequenced with a low cost in several days. NGS technology is similar to the traditional method, Sanger, which detects small DNA fragments by emitted signals at the time of synthesis of each fragment (from the DNA template), but the difference is that NGS can determine the massive simultaneous sequencing in a few days with high accuracy and the results are directly detected without the need for electrophoresis. In fact, NGS technology combines a variety of steps such as sample preparation, fragmentation of the sample of the studied genome, attachment of adapter to the ends of the fragments, imaging, and data analyses. In recent years, NGS technology continuously expanded the range of applications in different fields by reducing costs, increasing rates, and improving the quality of the data. The current review provided the potential applications of the NGS technology by emphasizing the diagnosis of the genetic diseases, identification of several types of cancers, prenatal screening, epigenetic modifications, personalized medicine, and identification of pathogens.

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“…The widespread availability of whole-genome and whole-exon sequencing in clinical practice and the continuing significant decrease in cost of sequencing have raised the question of whether traditional metabolic newborn screening might be replaced by genome sequencing [ 9 ]. It has been clearly shown that DNA amplified from both old and new dried blood spots performs as well as their whole-blood reference samples with regard to error rates, indicating that DBSs are excellent sources of DNA for next-generation sequencing studies of disease [ 10 ].…”

mentioning

confidence: 99%

Ethical Issues Surrounding Newborn Screening

Howell

2021

IJNS

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It would be difficult to overestimate the importance of persistent, thoughtful parents and their importance in the development of treatments for their children’s rare disorders. Almost a century ago in Norway, observant parents led a brilliant young physician-scientist to his discovery of the underlying cause of their children’s profound developmental delay—i.e., phenylketonuria, or PKU. Decades later, in a recovering war-ravaged Britain, an equally persistent mother pressed the scientists at Birmingham Children’s Hospital to find a way to treat her seriously damaged daughter, Sheila, who suffered from PKU. Living on the financial edge, this mother insisted that Bickel and colleagues develop such a diet, and she volunteered Sheila to be the patient in the trial. The scientists concluded that the low phenylalanine diet helped but needed to be started very early—so, newborn screening was born to permit the implementation of this. Many steps brought us to where we are today, but these courageous parents made it all begin.

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Challenges of using next generation sequencing in newborn screening

Cited by 22 publications

References 29 publications

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

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

Strategies, Quality Control and Clinical Applications of Next Generation Sequencing

Ethical Issues Surrounding Newborn Screening

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