Methodology article

Genome-wide scans using archived neonatal dried blood spot samples

Mads V Hollegaard^1,2 , Jonas Grauholm³ , Anders Børglum⁴ , Mette Nyegaard⁴ , Bent Nørgaard-Pedersen¹ , Torben Ørntoft^3,5 , Preben B Mortensen⁶ , Carsten Wiuf⁷ , Ole Mors⁸ , Michael Didriksen⁹ , Poul Thorsen¹⁰ and David M Hougaard¹

¹  Section of Neonatal Screening and Hormones, Statens Serum Institut, Copenhagen, DK-2300, Denmark

²  Department of Epidemiology, University of Aarhus, Aarhus, DK-8000, Denmark

³  AROS Applied Biotechnology A/S, Aarhus, DK-8000, Denmark

⁴  Institute of Human Genetics, University of Aarhus, Aarhus, DK-8000, Denmark

⁵  Department of Clinical Biochemistry, Skejby Sygehus, Aarhus, DK-8000, Denmark

⁶  The National Centre for Register Based Research, University of Aarhus, Aarhus, DK-8000, Denmark

⁷  Bioinformatics Research Center, University of Aarhus, Aarhus, DK-8000, Denmark

⁸  Centre for Psychiatric Research, Aarhus University Hospital Risskov, Aarhus, DK-8000, Denmark

⁹  Lundbeck A/S, Taastrup, DK-2630, Denmark

¹⁰  Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

author email corresponding author email

BMC Genomics 2009, 10:297doi:10.1186/1471-2164-10-297

Published:	4 July 2009

Abstract

Background

Identification of disease susceptible genes requires access to DNA from numerous well-characterised subjects. Archived residual dried blood spot samples from national newborn screening programs may provide DNA from entire populations and medical registries the corresponding clinical information. The amount of DNA available in these samples is however rarely sufficient for reliable genome-wide scans, and whole-genome amplification may thus be necessary. This study assess the quality of DNA obtained from different amplification protocols by evaluating fidelity and robustness of the genotyping of 610,000 single nucleotide polymorphisms, using the Illumina Infinium HD Human610-Quad BeadChip. Whole-genome amplified DNA from 24 neonatal dried blood spot samples stored between 15 to 25 years was tested, and high-quality genomic DNA from 8 of the same individuals was used as reference.

Results

Using 3.2 mm disks from dried blood spot samples the optimal DNA-extraction and amplification protocol resulted in call-rates between 99.15% – 99.73% (mean 99.56%, N = 16), and conflicts with reference DNA in only three per 10,000 genotype calls.

Conclusion

Whole-genome amplified DNA from archived neonatal dried blood spot samples can be used for reliable genome-wide scans and is a cost-efficient alternative to collecting new samples.