Genome-wide scans using archived neonatal dried blood spot samples.
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.


CONCLUSIONS
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.
Hollegaard
Mads V
MV
Section of Neonatal Screening and Hormones, Statens Serum Institut, Copenhagen, Denmark. mvh@ssi.dk
Grauholm
Jonas
J
Børglum
Anders
A
Nyegaard
Mette
M
Nørgaard-Pedersen
Bent
B
Ørntoft
Torben
T
Mortensen
Preben B
PB
Wiuf
Carsten
C
Mors
Ole
O
Didriksen
Michael
M
Thorsen
Poul
P
Hougaard
David M
DM
D001774:Blood Chemical Analysis / Q000379:methods*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D013048:Specimen Handling
D004247:DNA