Genetical genomics has been suggested as a powerful approach to study the genotype-phenotype gap. However, the relatively low power of these experiments (usually related to the high cost) has hindered fulfillment of its promise, especially for loci (QTL) of moderate effects.One strategy with which to overcome the issue is to use a targeted approach. It has two clear advantages: (i) it reduces the problem to a simple comparison between different genotypic groups at the QTL and (ii) it is a good starting point from which to investigate downstream effects of the QTL. In this study, from 698 F2 birds used for QTL mapping, gene expression profiles of 24 birds with divergent homozygous QTL genotypes were investigated. The targeted QTL was on chromosome 1 and affected initial pH of breast muscle. The biological mechanisms controlling this trait can be similar to those affecting malignant hyperthermia or muscle fatigue in humans. The gene expression study identified 10 strong local signals that were markedly more significant compared to any genes on the rest of the genome. The differentially expressed genes all mapped to a region ,1 Mb, suggesting a remarkable reduction of the QTL interval. These results, combined with analysis of downstream effect of the QTL using gene network analysis, suggest that the QTL is controlling pH by governing oxidative stress. The results were reproducible with use of as few as four microarrays on pooled samples (with lower significance level). The results demonstrate that this cost-effective approach is promising for characterization of QTL.
EXISTING genetic variation provides a valuable resource for dissection of the genetic architecture of complex traits. Despite rapid developments in genetic and genomic tools, fine dissection of complex traits has remained challenging (Ron and Weller 2007). Many genetic studies have successfully mapped and identified chromosomal regions controlling these traits, but very few succeeded in further characterization and identification of genes and causative mutations. The extent to which protein-coding changes vs. regulatory changes contribute to the variation in complex traits is not clear. However, much of the naturally occurring variation in complex traits is believed to be partially controlled by regulatory elements. Changes in these regulatory elements, either at a single nucleotide level or more complex structural changes in the region, may underlie variations in gene expression (Guryev et al. 2008). Since its formal description (Jansen and Nap 2001), genetical genomics, the combined use of genetic mapping and expression profile (or other genomic information) in segregating populations, has shown to have great potential in addressing the issue. However, the successes to date do not match the original promise. One of the main reasons is the low power of the experiments linked to the low sample size due to high cost of such experiments, especially the genomic part of the study (De Koning and Haley 2005). One of the solutions proposed to address...