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Author Hollegaard, M.V.; Grove, J.; Grauholm, J.; Kreiner-Moller, E.; Bonnelykke, K.; Norgaard, M.; Benfield, T.L.; Norgaard-Pedersen, B.; Mortensen, P.B.; Mors, O.; Sorensen, H.T.; Harboe, Z.B.; Borglum, A.D.; Demontis, D.; Orntoft, T.F.; Bisgaard, H.; Hougaard, D.M. url  doi
  Title Robustness of genome-wide scanning using archived dried blood spot samples as a DNA source Type Journal Article
  Year (down) 2011 Publication BMC Genetics Abbreviated Journal BMC Genet  
  Volume 12 Issue Pages 58  
  Keywords Blood Specimen Collection; DNA/analysis/*blood; Denmark; Female; Genetic Predisposition to Disease/*genetics; Genetic Testing/*methods; *Genome-Wide Association Study; Humans; Infant, Newborn; Male; Polymorphism, Single Nucleotide; Sequence Analysis, DNA/methods; Specimen Handling  
  Abstract BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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.  
  Address Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Orestads Boulevard, Copenhagen, DK-2300, Denmark.  
  Corporate Author Thesis  
  Impact Factor 02,397 First Author Hollegaard, M.V. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Hougaard, D.M.  
  ISSN 1471-2156 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:21726430; PMCID:PMC3142526 Approved no  
  Call Number Serial 63  
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