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Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs

BACKGROUND: This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. METHODS: We simulated nine different breedi...

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Autores principales: Gonen, Serap, Jenko, Janez, Gorjanc, Gregor, Mileham, Alan J., Whitelaw, C. Bruce A., Hickey, John M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240390/
https://www.ncbi.nlm.nih.gov/pubmed/28093068
http://dx.doi.org/10.1186/s12711-016-0280-3
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author Gonen, Serap
Jenko, Janez
Gorjanc, Gregor
Mileham, Alan J.
Whitelaw, C. Bruce A.
Hickey, John M.
author_facet Gonen, Serap
Jenko, Janez
Gorjanc, Gregor
Mileham, Alan J.
Whitelaw, C. Bruce A.
Hickey, John M.
author_sort Gonen, Serap
collection PubMed
description BACKGROUND: This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. METHODS: We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive. For each scenario, we evaluated genetic gain, genetic variance [Formula: see text] , rate of change in inbreeding ([Formula: see text] ), number of distinct quantitative trait nucleotides (QTN) edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles. RESULTS: Gene drives enhanced the benefits of genome editing in seven ways: (1) they amplified the increase in genetic gain brought about by genome editing; (2) they amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them; (3) they enabled more rapid targeting of QTN with lesser effect for genome editing; (4) they distributed fixed editing resources across a larger number of distinct QTN across generations; (5) they focussed editing on a smaller number of QTN within a given generation; (6) they reduced the level of inbreeding when editing a subset of the sires; and (7) they increased the efficiency of converting genetic variation into genetic gain. CONCLUSIONS: Genome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency caused by editing, which results in even higher genetic gain over a shorter period of time with no impact on inbreeding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12711-016-0280-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-52403902017-01-19 Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs Gonen, Serap Jenko, Janez Gorjanc, Gregor Mileham, Alan J. Whitelaw, C. Bruce A. Hickey, John M. Genet Sel Evol Research Article BACKGROUND: This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. METHODS: We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive. For each scenario, we evaluated genetic gain, genetic variance [Formula: see text] , rate of change in inbreeding ([Formula: see text] ), number of distinct quantitative trait nucleotides (QTN) edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles. RESULTS: Gene drives enhanced the benefits of genome editing in seven ways: (1) they amplified the increase in genetic gain brought about by genome editing; (2) they amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them; (3) they enabled more rapid targeting of QTN with lesser effect for genome editing; (4) they distributed fixed editing resources across a larger number of distinct QTN across generations; (5) they focussed editing on a smaller number of QTN within a given generation; (6) they reduced the level of inbreeding when editing a subset of the sires; and (7) they increased the efficiency of converting genetic variation into genetic gain. CONCLUSIONS: Genome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency caused by editing, which results in even higher genetic gain over a shorter period of time with no impact on inbreeding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12711-016-0280-3) contains supplementary material, which is available to authorized users. BioMed Central 2017-01-04 /pmc/articles/PMC5240390/ /pubmed/28093068 http://dx.doi.org/10.1186/s12711-016-0280-3 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Gonen, Serap
Jenko, Janez
Gorjanc, Gregor
Mileham, Alan J.
Whitelaw, C. Bruce A.
Hickey, John M.
Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs
title Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs
title_full Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs
title_fullStr Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs
title_full_unstemmed Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs
title_short Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs
title_sort potential of gene drives with genome editing to increase genetic gain in livestock breeding programs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240390/
https://www.ncbi.nlm.nih.gov/pubmed/28093068
http://dx.doi.org/10.1186/s12711-016-0280-3
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