Fractioned DNA Pooling: A New Cost-Effective Strategy for Fine Mapping of Quantitative Trait Loci

Institute of Evolution, University of Haifa, Mount Carmel, Haifa 31905, Israel.
Genetics (Impact Factor: 5.96). 09/2007; 176(4):2611-23. DOI: 10.1534/genetics.106.070011
Source: PubMed


Selective DNA pooling (SDP) is a cost-effective means for an initial scan for linkage between marker and quantitative trait loci (QTL) in suitable populations. The method is based on scoring marker allele frequencies in DNA pools from the tails of the population trait distribution. Various analytical approaches have been proposed for QTL detection using data on multiple families with SDP analysis. This article presents a new experimental procedure, fractioned-pool design (FPD), aimed to increase the reliability of SDP mapping results, by "fractioning" the tails of the population distribution into independent subpools. FPD is a conceptual and structural modification of SDP that allows for the first time the use of permutation tests for QTL detection rather than relying on presumed asymptotic distributions of the test statistics. For situations of family and cross mapping design we propose a spectrum of new tools for QTL mapping in FPD that were previously possible only with individual genotyping. These include: joint analysis of multiple families and multiple markers across a chromosome, even when the marker loci are only partly shared among families; detection of families segregating (heterozygous) for the QTL; estimation of confidence intervals for the QTL position; and analysis of multiple-linked QTL. These new advantages are of special importance for pooling analysis with SNP chips. Combining SNP microarray analysis with DNA pooling can dramatically reduce the cost of screening large numbers of SNPs on large samples, making chip technology readily applicable for genomewide association mapping in humans and farm animals. This extension, however, will require additional, nontrivial, development of FPD analytical tools.

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Available from: Abraham B. Korol
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    • "This approach has also been used to detect significant changes in marker allele frequency through two cycles of recurrent selection (Moreau et al. 2004). A fractioned DNA pooling approach has also been used in which the tails of the population distribution are randomly allocated among a number of independent sub-pools (Sham et al. 2002; Brohede et al. 2005; Korol et al. 2007; Shifman et al. 2008). Selective genotyping and pooled DNA analysis have been shown to have significant advantages in terms of cost savings, compared to entire population analysis, with negligible practical disadvantages in terms of power of detection in medical genomics research (Knight and Sham 2006; Macgregor et al. 2008). "
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