Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs.
Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs.
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DOI：
10.1186/s12711-016-0280-3
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发表时间：
2017-01-04
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影响因子：
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通讯作者：
Hickey JM
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文献类型：
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作者：
Gonen S;Jenko J;Gorjanc G;Mileham AJ;Whitelaw CB;Hickey JM
本文使用模拟来探索基因驱动如何在家畜育种计划中增加遗传增益。基因驱动是自然发生的现象，它导致一条染色体上的突变将其自身复制到其同源染色体上。我们模拟了九种不同的育种和编辑场景，具有共同的整体结构。每个场景都从21代选择开始，然后是基于真实育种值的20代选择，其中育种者单独使用选择，选择与基因组编辑相结合，或者选择与基因组编辑和基因驱动相结合。在使用基因驱动的场景中，我们改变了成功整合基因驱动的概率。对于每种情况，我们评估了遗传增益、遗传方差、近亲繁殖的变化率（）、编辑的不同数量性状核苷酸（QTN）的数量、编辑的QTN的有利等位基因频率的增加率以及固定有利等位基因的时间。基因驱动以七种方式增强了基因组编辑的益处：（1）它们放大了基因组编辑带来的遗传增益的增加;（2）它们放大了有利等位基因频率的增加率，并减少了修复它们所需的时间;（3）它们能够更快速地靶向QTN，而对基因组编辑的影响较小。（4）他们将固定的编辑资源分布在不同世代的大量不同的QTN上;（5）他们将编辑集中在给定世代内的少量QTN上;（6）他们在编辑公畜的子集时降低了近亲繁殖的水平;（7）提高了遗传变异转化为遗传增益的效率。家畜育种中的基因组编辑导致遗传增益的短期、中期和长期增加。遗传增益的增加是因为编辑增加了群体中有利等位基因的频率。基因驱动加速了由编辑引起的等位基因频率的增加，这导致在较短的时间内获得更高的遗传增益，而对近亲繁殖没有影响。本文的在线版本（doi：10.1186/s12711-016-0280-3）包含补充材料，可供授权用户使用。
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. 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 , rate of change in inbreeding (), 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. 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. 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. The online version of this article (doi:10.1186/s12711-016-0280-3) contains supplementary material, which is available to authorized users.