Abstract

BackgroundGenome 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).MethodsMultiple 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.ResultsResponse 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.ConclusionsThis study showed that PAGE has great potential for application in livestock breeding programs, but inbreeding needs to be managed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-015-0135-3) contains supplementary material, which is available to authorized users.

Highlights

  • Genome editing (GE) is a method that enables specific nucleotides in the genome of an individual to be changed

  • The results showed that compared to genomic selection (GS) only, GS supplemented by promotion of alleles by genome editing (PAGE) enabled a much greater response to selection but that some strategies for PAGE resulted in much greater rates of inbreeding than genomic selection only (GS only)

  • PAGE is a new technique with a potential future application for increasing responses to selection for quantitative traits in livestock breeding programs

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Summary

Introduction

Genome editing (GE) is a method that enables specific nucleotides in the genome of an individual to be changed. 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). Livestock breeding programs aim at improving populations by increasing the genetic merit of traits of socioeconomic importance. These are typically quantitative traits that are affected by many quantitative trait nucleotides (QTN), most of which only have small effects [1]. Alternatives to these conventional selection methods will be required to overcome these limitations An example of such a method, proposed in this work, is promotion of alleles by genome editing (PAGE); which has the potential to enable rapid increases in the frequency of favourable alleles. PAGE offers the opportunity to move genetic variation between individuals in a population much more freely since it enables individual QTN alleles to be moved independently of all other QTN alleles

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