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

Abstract：

: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.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

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,Papassotiropoul

doi

10.1086/510686

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

126-39

issue

1

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(07)60927-6

journal_volume

80

pub_type

杂志文章

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