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        Microarray-Based Genome-Wide Association Studies Using Pooled DNA

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        Pooling genomic DNA samples within clinical classes of disease for use in whole-genome single nucleotide polymorphism (SNP) genotyping allows for rapid and inexpensive genome-wide association studies (GWAS). We describe here a general outline for combining hundreds of genomic DNA samples prior to genotyping on commercially available high-density SNP microarrays. The pool construction approach is universal, and independent of the SNP genotyping platform utilized, and therefore provides a quick, efficient, and low-cost alternative to interrogating thousands of individual samples on singular SNP microarrays. While the strategy for pooled DNA genotyping on SNP microarrays is straightforward, the success of such studies is critically dependent upon the accuracy of allelic frequency calculations, the �ability to identify falsely positive results arising from assay variability, and the willingness to better resolve association signals through investigation of neighboring SNPs.
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