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Potential of promotion of alleles by genome editing to improve quantitative traits in livestock breeding programs.

Jenko J, Gorjanc G, Cleveland MA, Varshney RK, Whitelaw CB, Woolliams JA, Hickey JM - Genet. Sel. Evol. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Overall design of the simulation
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Fig1: Overall design of the simulation

Mentions: Simulations were used to evaluate the potential of PAGE to increase the response to selection for quantitative traits in livestock breeding programs. Ten replicates of several scenarios were performed with the overall simulation scheme in Fig. 1. The simulations were designed to: (i) generate whole-genome sequence data, (ii) generate QTN that affect phenotypes, (iii) generate pedigree structures for a livestock population, and (iv) test different selection and PAGE strategies. Conceptually, the simulation scheme was divided into a historical and a future component. The historical component represented historical evolution and recent historical breeding efforts up to the present day under the assumption that livestock populations have been evolving for tens of thousands of years, followed by 21 recent generations of modern animal breeding with selection on breeding values for the simulated trait only. The future component represented 20 future generations of modern animal breeding in which the breeders had different options and technologies at their disposal (i.e., PAGE and GS). The historical animal breeding generations were denoted generations–20 to 0 and the future animal breeding generations were denoted 1 to 20.Fig. 1


Potential of promotion of alleles by genome editing to improve quantitative traits in livestock breeding programs.

Jenko J, Gorjanc G, Cleveland MA, Varshney RK, Whitelaw CB, Woolliams JA, Hickey JM - Genet. Sel. Evol. (2015)

Overall design of the simulation
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4487592&req=5

Fig1: Overall design of the simulation
Mentions: Simulations were used to evaluate the potential of PAGE to increase the response to selection for quantitative traits in livestock breeding programs. Ten replicates of several scenarios were performed with the overall simulation scheme in Fig. 1. The simulations were designed to: (i) generate whole-genome sequence data, (ii) generate QTN that affect phenotypes, (iii) generate pedigree structures for a livestock population, and (iv) test different selection and PAGE strategies. Conceptually, the simulation scheme was divided into a historical and a future component. The historical component represented historical evolution and recent historical breeding efforts up to the present day under the assumption that livestock populations have been evolving for tens of thousands of years, followed by 21 recent generations of modern animal breeding with selection on breeding values for the simulated trait only. The future component represented 20 future generations of modern animal breeding in which the breeders had different options and technologies at their disposal (i.e., PAGE and GS). The historical animal breeding generations were denoted generations–20 to 0 and the future animal breeding generations were denoted 1 to 20.Fig. 1

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.