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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.


Inbreeding coefficient 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 edits were performed in all of 25 or the top 10 sires or 100 edits were performed on the top five sires
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Fig11: Inbreeding coefficient 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 edits were performed in all of 25 or the top 10 sires or 100 edits were performed on the top five sires

Mentions: The average coefficient of inbreeding increased with each generation (Fig. 11). There was almost no difference in the rate of inbreeding between GS only and the GS + PAGE scenarios in which all sires were edited (i.e., A25se). However, GS + PAGE scenarios in which only a subset of the sires were edited resulted in a large increase in the rate of inbreeding compared to when all sires were edited. In addition, the rate of inbreeding for scenarios in which only five sires were edited (T5se) was much greater than for scenarios in which 10 sires were edited (T10se). After 20 generations of selection, the average inbreeding coefficient in generation 20 was 0.44 for GS only, 0.45 for GS + PAGE scenario A25se with 20 QTNe per sire, 0.53 for GS + PAGE scenario T10se with 20 QTNe per sire, and 0.65 for GS + PAGE scenario T5se with 100 QTNe per sire. There was no difference in inbreeding level between scenarios for which the top 10 (T10se) or bottom 10 (B10se) sires were edited (results not shown).Fig. 11


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)

Inbreeding coefficient 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 edits were performed in all of 25 or the top 10 sires or 100 edits were performed on the top five sires
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig11: Inbreeding coefficient 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 edits were performed in all of 25 or the top 10 sires or 100 edits were performed on the top five sires
Mentions: The average coefficient of inbreeding increased with each generation (Fig. 11). There was almost no difference in the rate of inbreeding between GS only and the GS + PAGE scenarios in which all sires were edited (i.e., A25se). However, GS + PAGE scenarios in which only a subset of the sires were edited resulted in a large increase in the rate of inbreeding compared to when all sires were edited. In addition, the rate of inbreeding for scenarios in which only five sires were edited (T5se) was much greater than for scenarios in which 10 sires were edited (T10se). After 20 generations of selection, the average inbreeding coefficient in generation 20 was 0.44 for GS only, 0.45 for GS + PAGE scenario A25se with 20 QTNe per sire, 0.53 for GS + PAGE scenario T10se with 20 QTNe per sire, and 0.65 for GS + PAGE scenario T5se with 100 QTNe per sire. There was no difference in inbreeding level between scenarios for which the top 10 (T10se) or bottom 10 (B10se) sires were edited (results not shown).Fig. 11

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.