Complex traits analysis of chicken growth using targeted genetical genomics.

Dissecting the genetic control of complex trait variation remains very challenging, despite many advances in technology. The aim of this study was to use a major growth quantitative trait locus (QTL) in chickens mapped to chromosome 4 as a model for a targeted approach to dissect the QTL. We applied a variant of the genetical genomics approach to investigate genome-wide gene expression differences between two contrasting genotypes of a marked QTL. This targeted approach allows the direct quantification of the link between the genotypes and the genetic responses, thus narrowing the QTL-phenotype gap using fewer samples (i.e. microarrays) compared with the genome-wide genetical genomics studies. Four differentially expressed genes were localized under the region of the QTL. One of these genes is a potential positional candidate gene (AADAT) that affects lysine and tryptophan metabolism and has alternative splicing variants between the two genotypes. In addition, the lysine and glycolysis metabolism pathways were significantly enriched for differentially expressed genes across the genome. The targeted approach provided a complementary route to fine mapping of QTL by characterizing the local and the global downstream effects of the QTL and thus generating further hypotheses about the action of that QTL.

Genetical genomics: combining gene expression with marker genotypes in poultry.

Microarrays have been widely implemented across the life sciences, although there is still debate on the most effective uses of such transcriptomics approaches. In genetical genomics, gene expression measurements are treated as quantitative traits, and genome regions affecting expression levels are denoted as expression QTL (eQTL). The detected eQTL can represent a locus that lies close to the gene that is being controlled (cis-acting) or one or more loci that are unlinked to the gene that is being controlled (trans-acting). One powerful outcome of genetical genomics is the reconstruction of genetic pathways underlying complex trait variation. Because of the modest size of experiments to date, genetical genomics may fall short of its promise to unravel genetic networks. We propose to combine expression studies with fine mapping of functional trait loci. This synergistic approach facilitates the implementation of genetical genomics for species without inbred resources but is equally applicable to model species. Among livestock species, poultry is well placed to embrace this technology with the availability of the chicken genome sequence, microarrays for various platforms, as well as experimental populations in which QTL have been mapped. In the buildup toward full-blown eQTL studies, we can study the effects of known candidate genes or marked QTL at the gene expression level in more focused studies. To demonstrate the potential of genetical genomics, we have identified the cis and trans effects for a functional BW QTL on chicken chromosome 4 in breast tissue samples from chickens with contrasting QTL genotypes.