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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.


Mean frequency of the favourable alleles at all QTN that segregated at generation 0 or at the 20 QTN with the largest effect that segregated at generation 0 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 20 QTN were edited in all of the 25 selected sires
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Fig7: Mean frequency of the favourable alleles at all QTN that segregated at generation 0 or at the 20 QTN with the largest effect that segregated at generation 0 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 20 QTN were edited in all of the 25 selected sires

Mentions: In generation–20, the average frequency of favourable alleles at all QTN was 0.50. Selection using GS only increased the average frequency of favourable alleles by 0.05 from generation–20 to 0 (Fig. 7). Between generations 0 and 20, the frequency of favourable alleles increased by 0.02 for GS only and by 0.04 for the GS + PAGE scenario A25se with 20 QTNe per sire. GS only and GS + PAGE had different patterns of change in the average frequency of the favourable alleles at the QTN with the largest effects and these were also noticeably different from the change in the average frequency of the favourable alleles at all QTN. The average frequency of the favourable alleles at the 20 QTN with the largest effects for the GS + PAGE scenario A25se with 20 QTNe per sire, increased rapidly in the first three to four generations of GS + PAGE (Fig. 7). By generation 5, the average allele frequencies were already higher than 0.99, and full fixation was reached within 12 generations. For GS only, the favourable allele frequency of the 20 QTN with the largest effects increased approximately linearly up to generation 12, but at a considerably lower rate than for GS + PAGE scenarios. After generation 12, the rate of fixation of favourable alleles of the 20 QTN with the largest effects started to plateau at a value of less than 0.8 for GS only. As the number of QTNe increased, the trends of fixation for the other GS + PAGE scenarios became more similar to those for 20 QTNe per sire [See Additional file 2: Figure S2].Fig. 7


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)

Mean frequency of the favourable alleles at all QTN that segregated at generation 0 or at the 20 QTN with the largest effect that segregated at generation 0 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 20 QTN were edited in all of the 25 selected sires
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig7: Mean frequency of the favourable alleles at all QTN that segregated at generation 0 or at the 20 QTN with the largest effect that segregated at generation 0 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 20 QTN were edited in all of the 25 selected sires
Mentions: In generation–20, the average frequency of favourable alleles at all QTN was 0.50. Selection using GS only increased the average frequency of favourable alleles by 0.05 from generation–20 to 0 (Fig. 7). Between generations 0 and 20, the frequency of favourable alleles increased by 0.02 for GS only and by 0.04 for the GS + PAGE scenario A25se with 20 QTNe per sire. GS only and GS + PAGE had different patterns of change in the average frequency of the favourable alleles at the QTN with the largest effects and these were also noticeably different from the change in the average frequency of the favourable alleles at all QTN. The average frequency of the favourable alleles at the 20 QTN with the largest effects for the GS + PAGE scenario A25se with 20 QTNe per sire, increased rapidly in the first three to four generations of GS + PAGE (Fig. 7). By generation 5, the average allele frequencies were already higher than 0.99, and full fixation was reached within 12 generations. For GS only, the favourable allele frequency of the 20 QTN with the largest effects increased approximately linearly up to generation 12, but at a considerably lower rate than for GS + PAGE scenarios. After generation 12, the rate of fixation of favourable alleles of the 20 QTN with the largest effects started to plateau at a value of less than 0.8 for GS only. As the number of QTNe increased, the trends of fixation for the other GS + PAGE scenarios became more similar to those for 20 QTNe per sire [See Additional file 2: Figure S2].Fig. 7

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.