Optimal Design of Genetic Studies of Gene Expression with Two-colour Microarrays in Outbred Crosses

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" maximises 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-colour 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.

Key Words: Expression Quantitative Trait Loci (eQTL), optimal design, outbred F2 crosses, two-colour microarray

Online ISSN: 1943-2361  Print ISSN: 0016-6731
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