Background: Genotyping technology has advanced such that genome-wide association studies of complex diseases based upon dense marker maps are now technically feasible. However, the cost of such projects remains high. Pooled DNA genotyping offers the possibility of applying the same technologies at a fraction of the cost, and there is some evidence that certain ultra-high throughput platforms also perform with an acceptable accuracy. However, thus far, this conclusion is based upon published data concerning only a small number of SNPs.
Results: In the current study we prepared DNA pools from the parents and from the offspring of 30 parent-child trios that have been extensively genotyped by the HapMap project. We analysed the two pools with Affymetrix 10 K Xba 142 2.0 Arrays. The availability of the HapMap data allowed us to validate the performance of 6843 SNPs for which we had both complete individual and pooled genotyping data. Pooled analyses averaged over 5-6 microarrays resulted in highly reproducible results. Moreover, the accuracy of estimating differences in allele frequency between pools using this ultra-high throughput system was comparable with previous reports of pooling based upon lower throughput platforms, with an average error for the predicted allelic frequencies differences between the two pools of 1.37% and with 95% of SNPs showing an error of < 3.2%.
Conclusion: Genotyping thousands of SNPs with DNA pooling using Affymetrix microarrays produces highly accurate results and can be used for genome-wide association studies.