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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.


Cumulative response to selection across 21 generations of recent historical breeding based on genomic selection only (GS only) and 20 generations of future breeding based on GS only or genomic selection plus the promotion of alleles by genome editing (GS + PAGE) when a 125, b 250, or c 500 edits per generation were distributed across all of the 25 or the top 5 selected sires
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Fig6: Cumulative response to selection across 21 generations of recent historical breeding based on genomic selection only (GS only) and 20 generations of future breeding based on GS only or genomic selection plus the promotion of alleles by genome editing (GS + PAGE) when a 125, b 250, or c 500 edits per generation were distributed across all of the 25 or the top 5 selected sires

Mentions: When the total resources for PAGE were a limiting factor, the GS + PAGE scenarios in which a fixed number of QTNe per generation was distributed across a small number of sires, resulted in considerably more cumulative response to selection, compared to scenarios in which the same fixed number of QTNe per generation was distributed across a greater number of the sires (Fig. 6). For example, after 20 generations of GS + PAGE with 500 QTNe per generation, the cumulative response to selection for scenario T5se with 100 QTNe per sire was 4.12 times greater than that of GS only; while the cumulative response to selection for the scenario A25se with 20 QTNe per sire was only 2.00 times greater than that of GS only (Table 2). Therefore, the benefit of spreading the 500 QTNe per generation across the top five sires was 2.06 (i.e., 2.06 = 4.12/2.00) times greater than spreading them across all 25 sires. These trends were consistent across the range of total PAGE resources (i.e., totals of 125, 250, or 500 QTNe per generation). There was a noticeable difference in the shape of the response to selection across the generations of selection between scenarios A25se and the scenarios in which the PAGE resources were distributed across a small number of sires (T5se). In the first generation, distributing the edits across a small number of sires (T5se) never led to better results than distributing them across all sires (A25se) [See Additional file 1: Figure S1]. In the following generations, distributing the edits across a small number of sires improved response much more.Fig. 6


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)

Cumulative response to selection across 21 generations of recent historical breeding based on genomic selection only (GS only) and 20 generations of future breeding based on GS only or genomic selection plus the promotion of alleles by genome editing (GS + PAGE) when a 125, b 250, or c 500 edits per generation were distributed across all of the 25 or the top 5 selected sires
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: Cumulative response to selection across 21 generations of recent historical breeding based on genomic selection only (GS only) and 20 generations of future breeding based on GS only or genomic selection plus the promotion of alleles by genome editing (GS + PAGE) when a 125, b 250, or c 500 edits per generation were distributed across all of the 25 or the top 5 selected sires
Mentions: When the total resources for PAGE were a limiting factor, the GS + PAGE scenarios in which a fixed number of QTNe per generation was distributed across a small number of sires, resulted in considerably more cumulative response to selection, compared to scenarios in which the same fixed number of QTNe per generation was distributed across a greater number of the sires (Fig. 6). For example, after 20 generations of GS + PAGE with 500 QTNe per generation, the cumulative response to selection for scenario T5se with 100 QTNe per sire was 4.12 times greater than that of GS only; while the cumulative response to selection for the scenario A25se with 20 QTNe per sire was only 2.00 times greater than that of GS only (Table 2). Therefore, the benefit of spreading the 500 QTNe per generation across the top five sires was 2.06 (i.e., 2.06 = 4.12/2.00) times greater than spreading them across all 25 sires. These trends were consistent across the range of total PAGE resources (i.e., totals of 125, 250, or 500 QTNe per generation). There was a noticeable difference in the shape of the response to selection across the generations of selection between scenarios A25se and the scenarios in which the PAGE resources were distributed across a small number of sires (T5se). In the first generation, distributing the edits across a small number of sires (T5se) never led to better results than distributing them across all sires (A25se) [See Additional file 1: Figure S1]. In the following generations, distributing the edits across a small number of sires improved response much more.Fig. 6

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.