Comparison of gene editing versus conventional breeding to introgress the POLLED allele into the US dairy cattle population

Authors: MUELLER, MACI - University Of California, Davis; Cole, John; SONSTEGARD, TAD - Recombinetics, Inc; VAN EENENNAAM, ALISON - University Of California, Davis

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/21/2019
Publication Date: 5/1/2019
Citation: Mueller, M.L., Cole, J.B., Sonstegard, T.S., Van Eenennaam, A.L. 2019. Comparison of gene editing versus conventional breeding to introgress the POLLED allele into the US dairy cattle population. Journal of Dairy Science. 102(5):4215-4226. https://doi.org/10.3168/jds.2018-15892.
DOI: https://doi.org/10.3168/jds.2018-15892

Interpretive Summary: Dehorning protects animals and humans from injury but is painful. Breeding for polled (hornlessness) has not been adopted due to the low genetic merit and scarcity of polled dairy sires. Alternatively, gene editing to produce high genetic merit polled sires has been proposed. We simulated the introgression of the POLLED allele into the U.S. dairy cattle population via conventional breeding or gene editing for 20 years. Gene editing only the top 1% of elite artificial insemination sires/year, resulted in the POLLED allele being rapidly disseminated while maintaining genetic diversity and genetic progress, which was superior to using existing polled genetics.

Technical Abstract: Disbudding and dehorning are commonly used cattle management practices to protect animals and humans from injury. They are unpleasant, costly processes subject to increased public scrutiny as an animal welfare issue. Horns are a recessively inherited trait, so one option to eliminate dehorning is to breed for polled (hornlessness). However, due to the low genetic merit and scarcity of polled dairy sires, this approach has not been widely adopted. In March 2018, there were only 3 Holstein and 0 Jersey active homozygous polled sires registered with the National Association of Animal Breeders. Alternatively, gene editing to produce high genetic merit polled sires has been proposed. To further explore this concept, introgression of the POLLED allele into both the U.S. Holstein and Jersey cattle populations via conventional breeding or gene editing (top 1% of bulls/year) was simulated for 3 polled mating schemes and compared to baseline selection on lifetime net merit (NM$) alone, over the course of 20 years. Scenarios were replicated 10 times and the change in HORNED allele frequency, inbreeding, genetic (NM$) gain and number of unique sires used was calculated. Gene editing decreased the frequency of the HORNED allele to < 0.1 after 20 years, which was as fast or faster than conventional breeding for both breeds. In the mating scheme that required the use of only existing homozygous polled sires, inbreeding reached 17% (Holstein) and 14% (Jersey), compared to less than 7% in the baseline scenario. However, gene editing in the same mating scheme resulted in significantly less inbreeding, 9% (Holstein) and 8% (Jersey). Also, gene editing resulted in significantly higher NM$ after 20 years compared to conventional breeding for both breeds. Additionally, the gene editing scenarios of both breeds used a significantly greater number of unique sires compared to either the conventional breeding or baseline scenarios. Overall, our simulations show that, given the current genetic merit of horned and polled dairy sires, the use of conventional breeding methods to decrease the frequency of the HORNED allele will increase inbreeding and slow genetic improvement. Furthermore, this study demonstrates how gene editing could be used to rapidly decrease the frequency of the HORNED allele in U.S. dairy cattle populations while maintaining the rate of genetic gain, constraining inbreeding to acceptable levels, and simultaneously addressing an emerging animal welfare concern.