title: Potential of promotion of alleles by genome editing to improve quantitative traits in livestock breeding programs.
abstract: BACKGROUND
  Genome editing (GE) is a method that enables specific nucleotides in the genome of an individual to be changed. To date, use of GE in livestock has focussed on simple traits that are controlled by a few quantitative trait nucleotides (QTN) with large effects. The aim of this study was to evaluate the potential of GE to improve quantitative traits that are controlled by many QTN, referred to here as promotion of alleles by genome editing (PAGE).
  
  
  METHODS
  Multiple scenarios were simulated to test alternative PAGE strategies for a quantitative trait. They differed in (i) the number of edits per sire (0 to 100), (ii) the number of edits per generation (0 to 500), and (iii) the extent of use of PAGE (i.e. editing all sires or only a proportion of them). The base line scenario involved selecting individuals on true breeding values (i.e., genomic selection only (GS only)-genomic selection with perfect accuracy) for several generations. Alternative scenarios complemented this base line scenario with PAGE (GS + PAGE). The effect of different PAGE strategies was quantified by comparing response to selection, changes in allele frequencies, the number of distinct QTN edited, the sum of absolute effects of the edited QTN per generation, and inbreeding.
  
  
  RESULTS
  Response to selection after 20 generations was between 1.08 and 4.12 times higher with GS + PAGE than with GS only. Increases in response to selection were larger with more edits per sire and more sires edited. When the total resources for PAGE were limited, editing a few sires for many QTN resulted in greater response to selection and inbreeding compared to editing many sires for a few QTN. Between the scenarios GS only and GS + PAGE, there was little difference in the average change in QTN allele frequencies, but there was a major difference for the QTN with the largest effects. The sum of the effects of the edited QTN decreased across generations.
  
  
  CONCLUSIONS
  This study showed that PAGE has great potential for application in livestock breeding programs, but inbreeding needs to be managed.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, Scotland, UK. janez.jenko@roslin.ed.ac.uk.
authors.forename: Janez
authors.initials: J
authors.lastname: Jenko
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, Scotland, UK. gregor.gorjanc@roslin.ed.ac.uk.
authors.forename: Gregor
authors.initials: G
authors.lastname: Gorjanc
authors.affiliation: , Genus plc.,100 Bluegrass Commons Blvd., Suite 2200, Hendersonville, TN, 37075, USA. matthew.cleveland@genusplc.com.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cleveland
authors.affiliation: International Crop Research Institute for the Semi-Arid Tropics (ICRISAT), Patancheru, India. r.k.varshney@cgiar.org.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Varshney
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, Scotland, UK. bruce.whitelaw@roslin.ed.ac.uk.
authors.forename: C Bruce A
authors.initials: CB
authors.lastname: Whitelaw
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, Scotland, UK. john.woolliams@roslin.ed.ac.uk.
authors.forename: John A
authors.initials: JA
authors.lastname: Woolliams
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian, Scotland, UK. john.hickey@roslin.ed.ac.uk.
authors.forename: John M
authors.initials: JM
authors.lastname: Hickey
mesh_terms: D000818:Animals; D005787:Gene Frequency; D014644:Genetic Variation; D016678:Genome; D058751:Livestock / Q000235:genetics*; D008957:Models, Genetic; D040641:Quantitative Trait Loci; D012641:Selection, Genetic; D000068618:Selective Breeding / Q000235:genetics*