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

Martin Johnsson, Robert Gaynor, Janez Jenko, Gregor Gorjanc, Dirk-Jan De Koning, John Hickey

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
JournalGenetics Selection Evolution
Early online date17 Apr 2019
Publication statusE-pub ahead of print - 17 Apr 2019


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