Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies

Pearson, John V. and Huentelman, Matthew J. and Halperin, Rebecca F. and Tembe, Waibhav D. and Melquist, Stacey and Homer, Nils and Brun, Marcel and Szelinger, Szabolcs and Coon, Keith D. and Zismann, Victoria L. and Webster, Jennifer A. and Beach, Thomas and Sando, Sigrid B. and Aasly, Jan O. and Heun, Reinhard and Jessen, Frank and Kolsch, Heike and Tsolaki, Magdalini and Daniilidou, Makrina and Reiman, Eric M. and Papassotiropoulos, Andreas and Hutton, Michael L. and Stephan, Dietrich A. and Craig, David W.. (2007) Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studies. American journal of human genetics, Vol. 80, H. 1. pp. 126-139.

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Official URL: http://edoc.unibas.ch/dok/A5257159

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We report the development and validation of experimental methods, study designs, and analysis software for pooling-based genomewide association (GWA) studies that use high-throughput single-nucleotide-polymorphism (SNP) genotyping microarrays. We first describe a theoretical framework for establishing the effectiveness of pooling genomic DNA as a low-cost alternative to individually genotyping thousands of samples on high-density SNP microarrays. Next, we describe software called "GenePool," which directly analyzes SNP microarray probe intensity data and ranks SNPs by increased likelihood of being genetically associated with a trait or disorder. Finally, we apply these methods to experimental case-control data and demonstrate successful identification of published genetic susceptibility loci for a rare monogenic disease (sudden infant death with dysgenesis of the testes syndrome), a rare complex disease (progressive supranuclear palsy), and a common complex disease (Alzheimer disease) across multiple SNP genotyping platforms. On the basis of these theoretical calculations and their experimental validation, our results suggest that pooling-based GWA studies are a logical first step for determining whether major genetic associations exist in diseases with high heritability.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Life Sciences Training Facility (Papassotiropoulos)
07 Faculty of Psychology > Departement Psychologie > Ehemalige Einheiten Psychologie > Molecular Neuroscience (Papassotiropoulos)
UniBasel Contributors:Papassotiropoulos, Andreas
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Univ. of Chicago Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:22
Deposited On:22 Mar 2012 13:28

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