Utility of the pooling approach as applied to whole genome association scans with high-density Affymetrix microarrays.
BACKGROUND
We report an attempt to extend the previously successful approach of combining SNP (single nucleotide polymorphism) microarrays and DNA pooling (SNP-MaP) employing high-density microarrays. Whereas earlier studies employed a range of Affymetrix SNP microarrays comprising from 10 K to 500 K SNPs, this most recent investigation used the 6.0 chip which displays 906,600 SNP probes and 946,000 probes for the interrogation of CNVs (copy number variations). The genotyping assay using the Affymetrix SNP 6.0 array is highly demanding on sample quality due to the small feature size, low redundancy, and lack of mismatch probes.


RESULTS
In the first study published so far using this microarray on pooled DNA, we found that pooled cheek swab DNA could not accurately predict real allele frequencies of the samples that comprised the pools. In contrast, the allele frequency estimates using blood DNA pools were reasonable, although inferior compared to those obtained with previously employed Affymetrix microarrays. However, it might be possible to improve performance by developing improved analysis methods.


CONCLUSIONS
Despite the decreasing costs of genome-wide individual genotyping, the pooling approach may have applications in very large-scale case-control association studies. In such cases, our study suggests that high-quality DNA preparations and lower density platforms should be preferred.
MRC SGDP Centre, Institute of Psychiatry, King's College London, London, UK. alexandra.schosser@kcl.ac.uk.
Alexandra
A
Schosser
Katrina
K
Pirlo
Darya
D
Gaysina
Sarah
S
Cohen-Woods
Leonard C
LC
Schalkwyk
Amanda
A
Elkin
Ania
A
Korszun
Cerisse
C
Gunasinghe
Joanna
J
Gray
Lisa
L
Jones
Emma
E
Meaburn
Anne E
AE
Farmer
Ian W
IW
Craig
Peter
P
McGuffin