Utility of whole-genome sequencing for detection of newborn screening disorders in a population cohort of 1,696 neonates View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-03

AUTHORS

Dale L. Bodian, Elisabeth Klein, Ramaswamy K. Iyer, Wendy S. W. Wong, Prachi Kothiyal, Daniel Stauffer, Kathi C. Huddleston, Amber D. Gaither, Irina Remsburg, Alina Khromykh, Robin L. Baker, George L. Maxwell, Joseph G. Vockley, John E. Niederhuber, Benjamin D. Solomon

ABSTRACT

PURPOSE: To assess the potential of whole-genome sequencing (WGS) to replicate and augment results from conventional blood-based newborn screening (NBS). METHODS: Research-generated WGS data from an ancestrally diverse cohort of 1,696 infants and both parents of each infant were analyzed for variants in 163 genes involved in disorders included or under discussion for inclusion in US NBS programs. WGS results were compared with results from state NBS and related follow-up testing. RESULTS: NBS genes are generally well covered by WGS. There is a median of one (range: 0-6) database-annotated pathogenic variant in the NBS genes per infant. Results of WGS and NBS in detecting 28 state-screened disorders and four hemoglobin traits were concordant for 88.6% of true positives (n = 35) and 98.9% of true negatives (n = 45,757). Of the five infants affected with a state-screened disorder, WGS identified two whereas NBS detected four. WGS yielded fewer false positives than NBS (0.037 vs. 0.17%) but more results of uncertain significance (0.90 vs. 0.013%). CONCLUSION: WGS may help rule in and rule out NBS disorders, pinpoint molecular diagnoses, and detect conditions not amenable to current NBS assays. More... »

PAGES

221

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/gim.2015.111

DOI

http://dx.doi.org/10.1038/gim.2015.111

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017168184

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26334177


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HOW TO GET THIS DATA PROGRAMMATICALLY:

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curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/gim.2015.111'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/gim.2015.111'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/gim.2015.111'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/gim.2015.111'


 

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