Completion of the human genome sequence provides a foundation for understanding genetic complexity and how it contributes to diverse phenotypes and disease. It is clear that model organisms will continue to play an invaluable role in the synthesis of this understanding. The pig represents an evolutionary Glade distinct from primates or rodents and thus, provides considerable power in the analysis of DNA sequence and phenotypic diversity. The pig, a domesticated eutherian mammal, has coevolved with humans and represents a taxon with diverse selected phenotypes. The pig has played a central role in the scientific and medical communities, thus providing scientific justification for understanding the porcine genome with respect to physiological models of growth and development, health, and reproduction. The recent ability to genetically modify the porcine genome, genetically manipulate embryonic fibroblasts, and ‘clone’ genetically modified somatic cells through nuclear transfer attests to how the pig can provide relevant genetic models of appropriate phenotypes and to resolve the genetic complexity of quantitative traits.
It has proven to be extremely difficult to identify the causal mutations underlying livestock quantitative trait loci (QTLs) and this has severely handicapped the application of marker-assisted selection (MAS) in commercial livestock species. The availability of a whole genome sequence will assist in the identification of candidate genes within a critical region harboring a QTL and also in the design of PCR primers to screen for diversity within coding and non-coding regulatory regions of targeted candidate genes. However it will not overcome the key problem for quantitative trait nucleotide (QTN) identification; viz., the recognition of the important regulatory regions and the identification of causal mutations within these regions. The central tenet of this paper is that new approaches are required for the successful implementation of MAS within commercial livestock populations. We propose that a useful paradigm will be to conduct whole genome scans for QTL within the populations in which MAS is to be employed allowing the application of MAS using linked-markers within these populations. This approach also has utility for QTN identification since the genome scan will identify unrelated or distantly related animals possessing alternative QTL genotypes which can be sequenced. This approach should provide an increased power for QTN identification over designed experimental crosses which often employ a small number of parents and that result in a limited number of haplotypes within the QTL critical region, often confounding many mutations with the causal QTN. In this paper, we describe our approach to QTL mapping, MAS and QTN identification using the U.S. Angus population as target population.