Management of Mendelian Traits in Breeding Programs by Gene Editing: A Simulation Study

Cole, J.B.

doi:10.1101/116459

Cited by 7 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The downside of selection against carriers is that the number of sires available for selection is reduced, with associated risks of inbreeding and loss of genetic variation. Van Eenennaam and Kinghorn [72] and Cole [34, 73] have extended mate selection schemes to penalize the use of carrier animals or to prevent matings between carriers. It is possible that such methods could be extended to use genome-wide deleterious load while maintaining diversity in other parts of the genome and maximizing the response to selection for production traits.…”

Section: Discussionmentioning

confidence: 99%

“…Genome editing is a suite of methods to modify the genomic DNA of an organism that allows not just insertion and deletion but replacement of sequences with a higher efficiency than previous methods, which involved difficult procedures such as microinjecting DNA into the nucleus of zygotes that produces engineered embryonic stem cells for implantation into chimeric embryos (reviewed by [30, 31]). Genome editing has shown theoretical promise for improving breeding progress by promoting favorable alleles [32, 33], and for managing recessive lethal variants [34]. Selection against carriers is the strategy of choice for removing monogenic recessive deleterious variants from animal breeding populations [5, 35].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Removal of alleles by genome editing (RAGE) against deleterious load

et al. 2019

View full text Add to dashboard Cite

Background In this paper, we simulate deleterious load in an animal breeding program, and compare the efficiency of genome editing and selection for decreasing it. Deleterious variants can be identified by bioinformatics screening methods that use sequence conservation and biological prior information about protein function. However, once deleterious variants have been identified, how can they be used in breeding? Results We simulated a closed animal breeding population that is subject to both natural selection against deleterious load and artificial selection for a quantitative trait representing the breeding goal. Deleterious load was polygenic and was due to either codominant or recessive variants. We compared strategies for removal of deleterious alleles by genome editing (RAGE) to selection against carriers. When deleterious variants were codominant, the best strategy for prioritizing variants was to prioritize low-frequency variants. When deleterious variants were recessive, the best strategy was to prioritize variants with an intermediate frequency. Selection against carriers was inefficient when variants were codominant, but comparable to editing one variant per sire when variants were recessive. Conclusions Genome editing of deleterious alleles reduces deleterious load, but requires the simultaneous editing of multiple deleterious variants in the same sire to be effective when deleterious variants are recessive. In the short term, selection against carriers is a possible alternative to genome editing when variants are recessive. Our results suggest that, in the future, there is the potential to use RAGE against deleterious load in animal breeding. Electronic supplementary material The online version of this article (10.1186/s12711-019-0456-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Removal of alleles by genome editing (RAGE) against deleterious load

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Computer simulation using the program “geneedit” ( Cole and Mueller, 2019 ) was used to compare introgression of the POLLED allele into the Australian Brahman population via conventional breeding or with the additional use of gene editing.…”

Section: Methodsmentioning

confidence: 99%

Comparison of Gene Editing Versus Conventional Breeding to Introgress the POLLED Allele Into the Tropically Adapted Australian Beef Cattle Population

et al. 2021

Self Cite

View full text Add to dashboard Cite

Dehorning is the process of physically removing horns to protect animals and humans from injury, but the process is costly, unpleasant, and faces increasing public scrutiny. Genetic selection for polled (hornless), which is genetically dominant to horned, is a long-term solution to eliminate the need for dehorning. However, due to the limited number of polled Australian Brahman bulls, the northern Australian beef cattle population remains predominantly horned. The potential to use gene editing to produce high-genetic-merit polled cattle was recently demonstrated. To further explore the concept, this study simulated introgression of the POLLED allele into a tropically adapted Australian beef cattle population via conventional breeding or gene editing (top 1% or 10% of seedstock bulls/year) for 3 polled mating schemes and compared results to baseline selection on genetic merit (Japan Ox selection index, $JapOx) alone, over the course of 20 years. The baseline scenario did not significantly decrease the 20-year HORNED allele frequency (80%), but resulted in one of the fastest rates of genetic gain ($8.00/year). Compared to the baseline, the conventional breeding scenarios where polled bulls were preferentially used for breeding, regardless of their genetic merit, significantly decreased the 20-year HORNED allele frequency (30%), but resulted in a significantly slower rate of genetic gain ($6.70/year, P ≤ 0.05). The mating scheme that required the exclusive use of homozygous polled bulls, resulted in the lowest 20-year HORNED allele frequency (8%), but this conventional breeding scenario resulted in the slowest rate of genetic gain ($5.50/year). The addition of gene editing the top 1% or 10% of seedstock bull calves/year to each conventional breeding scenario resulted in significantly faster rates of genetic gain (up to $8.10/year, P ≤ 0.05). Overall, our study demonstrates that, due to the limited number of polled Australian Brahman bulls, strong selection pressure on polled will be necessary to meaningfully increase the number of polled animals in this population. Moreover, these scenarios illustrate how gene editing could be a tool for accelerating the development of high-genetic-merit homozygous polled sires to mitigate the current trade-off of slower genetic gain associated with decreasing HORNED allele frequency in the Australian Brahman population.

show abstract

“…Geneedit.py ( Cole, 2017 ) simulated introgression of POLLED into the Jersey breed via conventional breeding or gene editing. The base population was 35,000 cows distributed over 200 herds and 350 bulls.…”

Section: Methodsmentioning

confidence: 99%