Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs

Background
This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome copying itself onto its homologous chromosome.

Methods
We used simulation to explore how gene drives can increase genetic gain. We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on TBV where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive.
For each scenario we evaluated genetic gain, genetic variance (, rate of change in inbreeding (), number of distinct QTN edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles.

Results
Gene drives enhanced the benefits of genome editing in seven ways:
i. They amplified the increase in genetic gain brought about by genome editing,
ii. They amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them,
iii. They enabled more rapid targeting of lesser effect QTN for genome editing,
iv. They distributed fixed editing resources across a larger number of distinct QTN across generations,
v. They focussed editing on a smaller number of QTN within a given generation,
vi. They reduced the level of inbreeding when editing a subset of the sires, and
vii. They increased the efficiency of converting genetic variation into genetic gain.

Conclusions
Genome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency caused by editing, which results in even higher genetic gain over a shorter period of time with no impact on inbreeding.