Strategies for accommodating gene-edited sires and their descendants in genetic evaluations

Abstract

AbstractGene editing has the potential to expedite the rate of genetic gain for complex traits. However, changing nucleotides (i.e., QTN) in the genome can affect the additive genetic relationship among individuals and, consequently, impact genetic evaluations. Therefore, the objectives of this study were to estimate the impact of including gene-edited individuals in the genetic evaluation and investigate modeling strategies to mitigate potential errors. For that, a beef cattle population was simulated for nine generations (N = 13,100). Gene-edited sires (1, 25, or 50) were introduced in generation 8. The number of edited QTN was 1, 3, or 13. Genetic evaluations were performed using pedigree, genomic data, or a combination of both. Relationships were weighted based on the effect of the edited QTN. Comparisons were made using the accuracy, average absolute bias, and dispersion of the estimated breeding values (EBV). In general, the EBV of the first generation of progeny of gene-edited sires were associated with greater average absolute bias and overdispersion than the EBV of the progeny of non-gene-edited sires (P ≤ 0.001). Weighting the relationship matrices increased (P ≤ 0.001) the accuracy of EBV when the gene-edited sires were introduced by 3% and decreased (P ≤ 0.001) the average absolute bias and dispersion for the progeny of gene-edited sires. For the second generation of descendants of gene-edited sires, the absolute bias increased as the number of edited alleles increased; however, the rate of increase in absolute bias was 0.007 for each allele edited when the relationship matrices were weighted compared with 0.10 when the relationship matrices were not weighted. Overall, when gene-edited sires are included in genetic evaluations, error is introduced in the EBV, such that the EBV of progeny of gene-edited sires are underestimated. Hence, the progeny of gene-edited sires would be less likely to be selected to be parents of the next generation than what was expected based on their true genetic merit. Therefore, modeling strategies such as weighting the relationship matrices are essential to avoid incorrect selection decisions if animals that have been edited for QTN underlying complex traits are introduced into genetic evaluations.