Prospects for Positional Cloning of QTL in General Pedigrees using the Bovine Whole Genome Sequence

Abstract

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.