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Robustness of genome-wide scanning using archived dried blood spot samples as a DNA source

Mads V Hollegaard1*, Jakob Grove23, Jonas Grauholm4, Eskil Kreiner-Møller5, Klaus Bønnelykke5, Mette Nørgaard6, Thomas L Benfield78, Bent Nørgaard-Pedersen1, Preben B Mortensen9, Ole Mors10, Henrik T Sørensen6, Zitta B Harboe11, Anders D Børglum2, Ditte Demontis2, Torben F Ørntoft12, Hans Bisgaard5 and David M Hougaard1

  • * Corresponding author: Mads V Hollegaard

Author Affiliations

1 Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Ørestads Boulevard, Copenhagen, DK-2300, Denmark

2 Department of Human Genetics, University of Aarhus, Wilhelm Meyers Allé, DK-8000, Aarhus, Denmark

3 Bioinformatics Research Centre, University of Aarhus, C.F. Møllers Allé, DK-8000 Aarhus, Denmark

4 AROS Applied Biotechnology AS. Science Park Skejby, Brendstrupgaardvej, DK-8200, Aarhus, Denmark

5 Copenhagen Prospective Studies on Asthma in Childhood, Copenhagen University Hospital, Ledreborg Allé, DK-2820, Gentofte, Denmark

6 Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé, DK-8200, Aarhus, Denmark

7 Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark

8 Faculty of health Sciences, University of Copenhagen, Blegdamsvej, DK-2200, Copenhagen, Denmark

9 The National Centre for Register Based Research, Aarhus University, Taasingegade, DK-8000, Aarhus, Denmark

10 Centre for Psychiatric Research, Aarhus University Hospital Risskov, Skovagervej. DK-8240, Aarhus, Denmark

11 Department of Bacteriology, Mycology, and Parasitology, Statens Serum Institut, Ørestads Boulevard, DK-2300, Copenhagen, Denmark

12 Department of Molecular Medicine, Aarhus University Hospital Skejby, Brendstrupgårdsvej, DK-8200, Denmark

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BMC Genetics 2011, 12:58  doi:10.1186/1471-2156-12-58

Published: 4 July 2011



The search to identify disease-susceptible genes requires access to biological material from numerous well-characterized subjects. Archived residual dried blood spot (DBS) samples, also known as Guthrie cards, from national newborn screening programs may provide a DNA source for entire populations. Combined with clinical information from medical registries, DBS samples could provide a rich source for productive research. However, the amounts of DNA which can be extracted from these precious samples are minute and may be prohibitive for numerous genotypings. Previously, we demonstrated that DBS DNA can be whole-genome amplified and used for reliable genetic analysis on different platforms, including genome-wide scanning arrays. However, it remains unclear whether this approach is workable on a large sample scale. We examined the robustness of using DBS samples for whole-genome amplification following genome-wide scanning, using arrays from Illumina and Affymetrix.


This study is based on 4,641 DBS samples from the Danish Newborn Screening Biobank, extracted for three separate genome-wide association studies. The amount of amplified DNA was significantly (P < 0.05) affected by the year of storage and storage conditions. Nine (0.2%) DBS samples failed whole-genome amplification. A total of 4,586 (98.8%) samples met our criterion of success of a genetic call-rate above 97%. The three studies used different arrays, with mean genotyping call-rates of 99.385% (Illumina Infinium Human610-Quad), 99.722% (Illumina Infinium HD HumanOmni1-Quad), and 99.206% (Affymetrix Axiom Genome-Wide CEU). We observed a concordance rate of 99.997% in the 38 methodological replications, and 99.999% in the 27 technical replications. Handling variables such as time of storage, storage conditions and type of filter paper were shown too significantly (P < 0.05) affect the genotype call-rates in some of the arrays, although the effect was minimal.


Our study indicates that archived DBS samples from the Danish Newborn Screening Biobank represent a reliable resource of DNA for whole-genome amplification and subsequent genome-wide association studies. With call-rates equivalent to high quality DNA samples, our results point to new opportunities for using the neonatal biobanks available worldwide in the hunt for genetic components of disease.