Whole-Genome Sequencing Can Identify Clinically Relevant Variants from a Single Sub-Punch of a Dried Blood Spot Specimen
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 D...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/9/3/52 |
| _version_ | 1797579560657616896 |
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| author | David J. McBride Claire Fielding Taksina Newington Alexandra Vatsiou Harry Fischl Maya Bajracharya Vicki S. Thomson Louise J. Fraser Pauline A. Fujita Jennifer Becq Zoya Kingsbury Mark T. Ross Stuart J. Moat Sian Morgan |
| author_facet | David J. McBride Claire Fielding Taksina Newington Alexandra Vatsiou Harry Fischl Maya Bajracharya Vicki S. Thomson Louise J. Fraser Pauline A. Fujita Jennifer Becq Zoya Kingsbury Mark T. Ross Stuart J. Moat Sian Morgan |
| author_sort | David J. McBride |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T22:38:51Z |
| format | Article |
| id | doaj.art-1d0d217ac1d54d599cdda8b46aabf21d |
| institution | Directory Open Access Journal |
| issn | 2409-515X |
| language | English |
| last_indexed | 2024-03-10T22:38:51Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj.art-1d0d217ac1d54d599cdda8b46aabf21d2023-11-19T11:12:32ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2023-09-01935210.3390/ijns9030052Whole-Genome Sequencing Can Identify Clinically Relevant Variants from a Single Sub-Punch of a Dried Blood Spot SpecimenDavid J. McBride0Claire Fielding1Taksina Newington2Alexandra Vatsiou3Harry Fischl4Maya Bajracharya5Vicki S. Thomson6Louise J. Fraser7Pauline A. Fujita8Jennifer Becq9Zoya Kingsbury10Mark T. Ross11Stuart J. Moat12Sian Morgan13Illumina Cambridge Ltd., Cambridge CB21 6DF, UKIllumina Cambridge Ltd., Cambridge CB21 6DF, UKIllumina Cambridge Ltd., Cambridge CB21 6DF, UKIllumina Cambridge Ltd., Cambridge CB21 6DF, UKIllumina Cambridge Ltd., Cambridge CB21 6DF, UKIllumina Cambridge Ltd., Cambridge CB21 6DF, UKIllumina Cambridge Ltd., Cambridge CB21 6DF, UKIllumina Cambridge Ltd., Cambridge CB21 6DF, UKIllumina Inc., San Diego, CA 92122, USAIllumina Cambridge Ltd., Cambridge CB21 6DF, UKIllumina Cambridge Ltd., Cambridge CB21 6DF, UKIllumina Cambridge Ltd., Cambridge CB21 6DF, UKWales Newborn Screening Laboratory, University Hospital of Wales, Cardiff CF14 4XW, UKAll Wales Genetics Laboratory, University Hospital of Wales, Cardiff CF14 4XW, UKThe 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.https://www.mdpi.com/2409-515X/9/3/52whole genome sequencingnewborn screeningdried blood spotsDNA sequencingcystic fibrosisphenylketonuria |
| spellingShingle | David J. McBride Claire Fielding Taksina Newington Alexandra Vatsiou Harry Fischl Maya Bajracharya Vicki S. Thomson Louise J. Fraser Pauline A. Fujita Jennifer Becq Zoya Kingsbury Mark T. Ross Stuart J. Moat Sian Morgan Whole-Genome Sequencing Can Identify Clinically Relevant Variants from a Single Sub-Punch of a Dried Blood Spot Specimen International Journal of Neonatal Screening whole genome sequencing newborn screening dried blood spots DNA sequencing cystic fibrosis phenylketonuria |
| title | Whole-Genome Sequencing Can Identify Clinically Relevant Variants from a Single Sub-Punch of a Dried Blood Spot Specimen |
| title_full | Whole-Genome Sequencing Can Identify Clinically Relevant Variants from a Single Sub-Punch of a Dried Blood Spot Specimen |
| title_fullStr | Whole-Genome Sequencing Can Identify Clinically Relevant Variants from a Single Sub-Punch of a Dried Blood Spot Specimen |
| title_full_unstemmed | Whole-Genome Sequencing Can Identify Clinically Relevant Variants from a Single Sub-Punch of a Dried Blood Spot Specimen |
| title_short | Whole-Genome Sequencing Can Identify Clinically Relevant Variants from a Single Sub-Punch of a Dried Blood Spot Specimen |
| title_sort | whole genome sequencing can identify clinically relevant variants from a single sub punch of a dried blood spot specimen |
| topic | whole genome sequencing newborn screening dried blood spots DNA sequencing cystic fibrosis phenylketonuria |
| url | https://www.mdpi.com/2409-515X/9/3/52 |
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