Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Mar;18(3):221-30.
doi: 10.1038/gim.2015.111. Epub 2015 Sep 3.

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

Dale L Bodian  1 , Elisabeth Klein  1 , Ramaswamy K Iyer  1   2 , Wendy S W Wong  1 , Prachi Kothiyal  1 , Daniel Stauffer  1 , Kathi C Huddleston  1 , Amber D Gaither  3 , Irina Remsburg  3 , Alina Khromykh  1 , Robin L Baker  4 , George L Maxwell  5   6   7 , Joseph G Vockley  1   2 , John E Niederhuber  1   8 , Benjamin D Solomon  1   3   9
Affiliations
Free article

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

Dale L Bodian et al. Genet Med. 2016 Mar.
Free article

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.

PubMed Disclaimer

References

    1. Sci Transl Med. 2012 Oct 3;4(154):154ra135 - PubMed
    1. Bioinformatics. 2013 Aug 15;29(16):2041-3 - PubMed
    1. Nucleic Acids Res. 2014 Jan;42(Database issue):D764-70 - PubMed
    1. Genet Med. 2013 Nov;15(11):910-1 - PubMed
    1. J Pediatr. 2014 Jan;164(1):14-9 - PubMed

Publication types

LinkOut - more resources