The impact of genome editing on the introduction of monogenic traits in livestock.

BACKGROUND: Genome editing technologies provide new tools for genetic improvement and have the potential to become the next game changer in animal and plant breeding. The aim of this study was to investigate how genome editing in combination with genomic selection can accelerate the introduction of a monogenic trait in a livestock population as compared to genomic selection alone.

METHODS: A breeding population was simulated under genomic selection for a polygenic trait. After reaching Bulmer equilibrium, the selection objective was to increase the allele frequency of a monogenic trait, with or without genome editing, in addition to improving the polygenic trait. Scenarios were compared for time to fixation of the desired allele, selection response for the polygenic trait, and level of inbreeding. The costs, in terms of number of editing procedures, were compared to the benefits of having more animals with the desired phenotype of the monogenic trait. Effects of reduced editing efficiency were investigated.

RESULTS: In a population of 20,000 selection candidates per generation, the total number of edited zygotes needed to reach fixation of the desired allele was 22,118, 7072, or 3912 with, no, moderate, or high selection emphasis on the monogenic trait, respectively. Genome editing resulted in up to four-fold faster fixation of the desired allele when efficiency was 100%, while the loss in long-term selection response for the polygenic trait was up to seven-fold less compared to genomic selection alone. With moderate selection emphasis on the monogenic trait, introduction of genome editing led to a four-fold reduction in the total number of animals showing the undesired phenotype before fixation. However, with a currently realistic editing efficiency of 4%, the number of required editing procedures increased by 72% and loss in selection response increased eight-fold compared to 100% efficiency. With low efficiency, loss in selection response was 29% more compared to genomic selection alone.

CONCLUSIONS: Genome editing strongly decreased the time to fixation for a desired allele compared to genomic selection alone. Reduced editing efficiency had a major impact on the number of editing procedures and on the loss in selection response. In addition to ethical and welfare considerations of genome editing, a careful assessment of its technical costs and benefits is required.