Genome editing approaches to augment livestock breeding programs.

The prospect of genome editing offers a number of promising opportunities for livestock breeders. Firstly, these tools can be used in functional genomics to elucidate gene function, and identify causal variants underlying monogenic traits. Secondly, they can be used to precisely introduce useful genetic variation into structured livestock breeding programs. Such variation may include repair of genetic defects, the inactivation of undesired genes, and the moving of useful alleles and haplotypes between breeds in the absence of linkage drag. Editing could also be used to accelerate the rate of genetic progress by enabling the replacement of the germ cell lineage of commercial breeding animals with cells derived from genetically elite lines. In the future, editing may also provide a useful complement to evolving approaches to decrease the length of the generation interval through in vitro generation of gametes. For editing to be adopted, it will need to seamlessly integrate with livestock breeding schemes. This will likely involve introducing edits into multiple elite animals to avoid genetic bottlenecks. It will also require editing of different breeds and lines to maintain genetic diversity, and enable structured cross-breeding. This requirement is at odds with the process-based trigger and event-based regulatory approach that has been proposed for the products of genome editing by several countries. In the absence of regulatory harmony, researchers in some countries will have the ability to use genome editing in food animals, while others will not, resulting in disparate access to these tools, and ultimately the potential for global trade disruptions.

Comparison of economic returns among genetic evaluation strategies in a 2-tiered Charolais-sired beef cattle production system.

The objective of this study was to estimate economic returns and costs associated with 4 scenarios of genetic evaluation that combine genotypes, phenotypes, and pedigree information from a vertically integrated purebred (PB) and commercial (CM) beef cattle system. Inference was to a genetic evaluation for a production system producing Charolais terminal sires for 10,000 CM cows. The first genetic evaluation scenario, denoted PB_A, modeled a genetic evaluation in which pedigree information and phenotypes are available for PB seedstock animals. Scenario PB_H contained the same information as PB_A with the addition of 25K density (GeneSeek Genomic Profiler LD) single nucleotide polymorphism (SNP) genotypes from PB animals. Scenario PBCM_A contained pedigree records and phenotypes from PB and CM cattle. Scenario PBCM_H contained phenotypes, pedigree, and genotypes from the PB and CM animals. Estimates of prediction error variance, (co)variance, and selection index parameters were used to estimate accuracy of selection candidates (rTI) and genetic gain resulting from selection on an economic index in US dollars (ΔG). Annual costs and incomes were used to determine the 30-yr cumulative net present value (CNPV) per CM calf resulting from selection in these genetic evaluation scenarios. Adding genotypes and CM production phenotypes to genetic evaluation increased the rTI of selection candidates and ΔG across all 4 scenarios. Scenario PBCM_H produced the highest annual ΔG in the PB herd at US$11.91 per head. Including CM phenotypes and parentage testing in the genetic evaluation increased the time to breakeven from 12 yr in PB_A to 19 years in PBCM_A after accounting for the cost of that information. Adding CM phenotypes and genotypes increased the breakeven time from 12 yr in PB_H to 18 yr in PBCM_H. Scenario PB_H produced the highest 30-yr CNPV per slaughtered CM calf at US$371.16. These results using field data indicate that economically relevant rTI and ΔG can be realized by adding 25K SNP genotypes and CM phenotypes to genetic evaluation, but the additional cost of that data significantly delays the economic return to the enterprise.

Genetic modification of food animals.

Animal breeders have used a variety of methods in selective breeding programs to genetically improve food animal species. Recently this has included the use of both genetic engineering and genome editing, particularly for targeting improvement in traits for which there is no within-species or within-breed genetic variation. Both intraspecies and interspecies allele substitutions and gene knock-ins have been accomplished with genome editing tools, targeting a number of important traits. The regulatory status of such animals is unclear as the definition of a regulated article is not consistent among different regulatory agencies and organizations. In the absence of a harmonized global regulatory approach to the genetic improvement of animals, it will be difficult for breeders to effectively achieve sustainable breeding objectives.