Optimizing Sequencing Resources in Genotyped Livestock Populations Using Linear Programming.

Low-cost genome-wide single-nucleotide polymorphisms (SNPs) are routinely used in animal breeding programs. Compared to SNP arrays, the use of whole-genome sequence data generated by the next-generation sequencing technologies (NGS) has great potential in livestock populations. However, sequencing a large number of animals to exploit the full potential of whole-genome sequence data is not feasible. Thus, novel strategies are required for the allocation of sequencing resources in genotyped livestock populations such that the entire population can be imputed, maximizing the efficiency of whole genome sequencing budgets. We present two applications of linear programming for the efficient allocation of sequencing resources. The first application is to identify the minimum number of animals for sequencing subject to the criterion that each haplotype in the population is contained in at least one of the animals selected for sequencing. The second application is the selection of animals whose haplotypes include the largest possible proportion of common haplotypes present in the population, assuming a limited sequencing budget. Both applications are available in an open source program LPChoose. In both applications, LPChoose has similar or better performance than some other methods suggesting that linear programming methods offer great potential for the efficient allocation of sequencing resources. The utility of these methods can be increased through the development of improved heuristics.