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Originally published as Genetics Published Articles Ahead of Print on September 14, 2008.
Genetics, Vol. 180, 1691-1698, November 2008, Copyright © 2008
doi:10.1534/genetics.108.090308
Optimal Design of Genetic Studies of Gene Expression With Two-Color Microarrays in Outbred Crosses
Alex C. Lam*,
,1,
Jingyuan Fu
,
Ritsert C. Jansen,
Chris S. Haley* and
Dirk-Jan de Koning*
* Roslin Institute (Edinburgh) and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin Biocentre, Roslin, Midlothian EH25 9PS, United Kingdom, Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom and Groningen Bioinformatics Centre, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9751 NN, Haren, The Netherlands
1 Corresponding author: Roslin Institute (Edinburgh), Roslin, Midlothian EH25 9PS, United Kingdom.
E-mail: alex.lam{at}roslin.ed.ac.uk
Combining global gene-expression profiling and genetic analysis of natural allelic variation (genetical genomics) has great potential in dissecting the genetic pathways underlying complex phenotypes. Efficient use of microarrays is paramount in experimental design as the cost of conducting this type of study is high. For those organisms where recombinant inbred lines are available for mapping, the "distant pair design" maximizes the number of informative contrasts over all marker loci. Here, we describe an extension of this design, named the "optimal pair design," for use with F2 crosses between outbred lines. The performance of this design is investigated by simulation and compared to several other two-color microarray designs. We show that, for a given number of microarrays, the optimal pair design outperforms all other designs considered for detection of expression quantitative trait loci (eQTL) with additive effects by linkage analysis. We also discuss the suitability of this design for outbred crosses in organisms with large genomes and for detection of dominance.