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Whole-genome sequencing can identify clinically relevant variants from a single sub-punch of a dried blood spot specimen

McBride, David J., Fielding, Claire, Newington, Taksina, Vatsiou, Alexandra, Fischl, Harry, Bajracharya, Maya, Thomson, Vicki S., Fraser, Louise J., Fujita, Pauline A., Becq, Jennifer, Kingsbury, Zoya, Ross, Mark T., Moat, Stuart J. and Morgan, Sian 2023. Whole-genome sequencing can identify clinically relevant variants from a single sub-punch of a dried blood spot specimen. International Journal of Neonatal Screening 9 (3) , 52. 10.3390/ijns9030052

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The collection of dried blood spots (DBS) facilitates newborn screening for a variety of rare, but very serious conditions in healthcare systems around the world. Sub-punches of varying sizes (1.5–6 mm) can be taken from DBS specimens to use as inputs for a range of biochemical assays. Advances in DNA sequencing workflows allow whole-genome sequencing (WGS) libraries to be generated directly from inputs such as peripheral blood, saliva, and DBS. We compared WGS metrics obtained from libraries generated directly from DBS to those generated from DNA extracted from peripheral blood, the standard input for this type of assay. We explored the flexibility of DBS as an input for WGS by altering the punch number and size as inputs to the assay. We showed that WGS libraries can be successfully generated from a variety of DBS inputs, including a single 3 mm or 6 mm diameter punch, with equivalent data quality observed across a number of key metrics of importance in the detection of gene variants. We observed no difference in the performance of DBS and peripheral-blood-extracted DNA in the detection of likely pathogenic gene variants in samples taken from individuals with cystic fibrosis or phenylketonuria. WGS can be performed directly from DBS and is a powerful method for the rapid discovery of clinically relevant, disease-causing gene variants.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL:, Type: open-access
Publisher: MDPI
Date of First Compliant Deposit: 10 October 2023
Date of Acceptance: 6 September 2023
Last Modified: 11 Oct 2023 01:43

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