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Mol Genet Metab. 2013 Sep-Oct;110(1-2):65-72. doi: 10.1016/j.ymgme.2013.06.004. Epub 2013 Jun 13.

Archived neonatal dried blood spot samples can be used for accurate whole genome and exome-targeted next-generation sequencing.

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Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Artillerivej, Copenhagen, Denmark.


Dried blood spot samples (DBSS) have been collected and stored for decades as part of newborn screening programmes worldwide. Representing almost an entire population under a certain age and collected with virtually no bias, the Newborn Screening Biobanks are of immense value in medical studies, for example, to examine the genetics of various disorders. We have previously demonstrated that DNA extracted from a fraction (2×3.2mm discs) of an archived DBSS can be whole genome amplified (wgaDNA) and used for accurate array genotyping. However, until now, it has been uncertain whether wgaDNA from DBSS can be used for accurate whole genome sequencing (WGS) and exome sequencing (WES). This study examined two individuals represented by three different types of samples each: whole-blood (reference samples), 3-year-old DBSS spotted with reference material (refDBSS), and 27- to 29-year-old archived neonatal DBSS (neoDBSS) stored at -20°C in the Danish Newborn Screening Biobank. The reference samples were genotyped using an Illumina Omni2.5M array, and all samples were sequenced on a HighSeq2000 Paired-End flow cell. First, we compared the array single nucleotide polymorphism (SNP) genotype data to the single nucleotide variation (SNV) calls from the WGS and WES SNV calls. We also compared the WGS and WES reference sample SNV calls to the DBSS SNV calls. The overall performance of the archived DBSS was similar to the whole blood reference sample. Plotting the error rates relative to coverage revealed that the error rates of DBSS were similar to that of their reference samples. SNVs called with a coverage<×8 had error rates between 1.5 and 35%, whereas the error rates of SNVs called with a coverage≥8 were <1.5%. In conclusion, the wgaDNA amplified from both new and old neonatal DBSS perform as well as their whole-blood reference samples with regards to error rates, strongly indicating that neonatal DBSS collected shortly after birth and stored for decades comprise an excellent resource for NGS studies of disease.


DBSS; DNSB; Danish Newborn Screening Biobank; E1 error-rate; E2 error-rate; Guthrie cards; NGS; Neonatal dried blood spot samples; Next-generation sequencing; Ref; SNP; SNV; WES; WGS; Whole-exome sequencing; Whole-genome sequencing; adult whole blood gDNA reference sample; adult whole blood reference sample stored as a DBSS; base pair; bp; dried blood spot samples; gDNA; genomic DNA; neoDBSS; neonatal heel-prick whole-blood sample; next generation sequencing; one basepair discrepancy in SNV/SNP genotype calls; refDBSS; single nucleotide polymorphism; single nucleotide variation; two basepairs discrepancy in SNV/SNP genotype calls; wgaDNA; whole exome sequencing; whole-genome amplified DNA; whole-genome sequencing

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