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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.


Response to selection between pairs of subsequent generations 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 different numbers of QTN (1, 5, 10, or 20) were edited for all 25 sires
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Fig5: Response to selection between pairs of subsequent generations 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 different numbers of QTN (1, 5, 10, or 20) were edited for all 25 sires

Mentions: Quantifying response to selection from generation to generation revealed two trends (Fig. 5). First, the advantage of GS + PAGE over GS only was greater in the first few generations than in later generations because the segregating QTN with larger effects were used more effectively by GS + PAGE in the initial generations than by GS only. Second, in later generations, the relative contribution of PAGE to response to selection increased and the relative contribution to overall response to selection of GS decreased. This second trend arose because the contribution to response to selection declined more rapidly for GS than for PAGE, due to the greater impact of genetic drift and hitchhiking on the loss of favourable alleles in the GS only scenarios. For example, the response to selection for GS + PAGE for scenario A25se with 20 QTNe per sire was 1.91 times greater than response for GS only at generation 10 and 2.00 times greater at generation 20.Fig. 5


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)

Response to selection between pairs of subsequent generations 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 different numbers of QTN (1, 5, 10, or 20) were edited for all 25 sires
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Response to selection between pairs of subsequent generations 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 different numbers of QTN (1, 5, 10, or 20) were edited for all 25 sires
Mentions: Quantifying response to selection from generation to generation revealed two trends (Fig. 5). First, the advantage of GS + PAGE over GS only was greater in the first few generations than in later generations because the segregating QTN with larger effects were used more effectively by GS + PAGE in the initial generations than by GS only. Second, in later generations, the relative contribution of PAGE to response to selection increased and the relative contribution to overall response to selection of GS decreased. This second trend arose because the contribution to response to selection declined more rapidly for GS than for PAGE, due to the greater impact of genetic drift and hitchhiking on the loss of favourable alleles in the GS only scenarios. For example, the response to selection for GS + PAGE for scenario A25se with 20 QTNe per sire was 1.91 times greater than response for GS only at generation 10 and 2.00 times greater at generation 20.Fig. 5

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.