Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ardlie KG, Kruglyak L, Seielstad M (2002) Patterns of linkage disequilibrium in the human genome. Nat Rev Genet 3:299–309
Carlson CS, Eberle MA, Rieder MJ, Smith JD, Kruglyak L, Nickerson DA (2003) Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans. Nat Genet 33:518–521
Kruglyak L, Nickerson DA (2001) Variation is the spice of life. Nat Genet 27:234–236
Schaid DJ, Guenther JC, Christensen GB, Hebbring S, Rosenow C, Hilker CA, McDonnell SK, Cunningham JM, Slager SL, Blute ML, Thibodeau SN (2004) Comparison of microsatellites versus single-nucleotide polymorphisms in a genome linkage screen for prostate cancer-susceptibility loci. Am J Hum Genet 75(6):948–965
Botstein D, Risch N (2003) Nat Genet 33(Suppl):228–237
Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273:1516–1517
Pearson JV, Huentelman MJ, Halperin RF, Tembe WD, Melquist S, Homer N, Brun M, Szelinger S, Coon KD, Zismann VL, Webster JA, Beach T, Sando SB, Aasly JO, Heun R, Jessen F, Kolsch H, Tsolaki M, Daniilidou M, Reiman EM, Papassotiropoulos A, Hutton ML, Stephan DA, Craig DW (2007) Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies. Am J Hum Genet 80:126–139
Bansal A et al (2002) Association testing by DNA pooling: an effective initial screen. Proc Natl Acad Sci USA 99:16871–16874
Meaburn E, Butcher LM, Schalkwyk LC, Plomin R (2006) Genotyoping pooled DNA using 100K SNP microarrays: a step towards genomewide association scans. Nucleic Acids Res 34:e27
Hinds DA et al (2004) Application of pooled genotyping to scan candidate regions for association with HDL cholesterol levels. Hum Genomics 1:421–434
Barratt BJ et al (2002) Identification of the sources of error in allele frequency estimations from pooled DNA indicates an optimal experimental design. Ann Hum Genet 66:393–405
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Szelinger, S., Pearson, J.V., Craig, D.W. (2011). Microarray-Based Genome-Wide Association Studies Using Pooled DNA. In: DiStefano, J. (eds) Disease Gene Identification. Methods in Molecular Biology, vol 700. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61737-954-3_4
Download citation
DOI: https://doi.org/10.1007/978-1-61737-954-3_4
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-953-6
Online ISBN: 978-1-61737-954-3
eBook Packages: Springer Protocols