Potential of promotion of alleles by genome editing to improve quantitative traits in livestock breeding programs.
Potential of promotion of alleles by genome editing to improve quantitative traits in livestock breeding programs.
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DOI：
10.1186/s12711-015-0135-3
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发表时间：
2015-07-02
期刊：
影响因子：
--
通讯作者：
Hickey JM
中科院分区：
文献类型：
--
作者：
Jenko J;Gorjanc G;Cleveland MA;Varshney RK;Whitelaw CB;Woolliams JA;Hickey JM
基因组编辑（GE）是一种能够改变个体基因组中特定核苷酸的方法。到目前为止，转基因在家畜中的应用主要集中在由几个数量性状核苷酸（QTN）控制的简单性状上。本研究的目的是评估GE改善由许多QTN控制的数量性状的潜力，这里称为通过基因组编辑（PAGE）促进等位基因。模拟了多个场景来测试数量性状的替代PAGE策略。它们的不同之处在于（i）每头公牛的编辑次数（0到100），（ii）每代的编辑次数（0到500），以及（iii）PAGE的使用程度（即编辑所有公牛或仅编辑其中的一部分）。基线方案涉及根据真实育种值（即，仅基因组选择（仅GS）-具有完美准确性的基因组选择）进行几代。替代方案补充了这一基线方案与PAGE（GS + PAGE）。通过比较对选择的响应、等位基因频率的变化、编辑的不同QTN的数量、每代编辑的QTN的绝对效应的总和和近交来量化不同PAGE策略的效应。20代后的选择响应是GS + PAGE的1.08 - 4.12倍。随着每头公鹿被编辑次数的增加和被编辑的公鹿的增加，对选择的反应增加的幅度更大。当PAGE的总资源有限时，与为几个QTN编辑许多公畜相比，为多个QTN编辑几个公畜导致对选择和近交的更大响应。在仅GS和GS + PAGE两种情况下，QTN等位基因频率的平均变化差异不大，但效应最大的QTN差异较大。编辑的QTN的影响之和在几代人之间下降。这项研究表明，聚丙烯酰胺凝胶电泳在家畜育种计划中具有很大的应用潜力，但需要管理近亲繁殖。本文的在线版本（doi：10.1186/s12711-015-0135-3）包含补充材料，可供授权用户使用。
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). 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. 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. This study showed that PAGE has great potential for application in livestock breeding programs, but inbreeding needs to be managed. The online version of this article (doi:10.1186/s12711-015-0135-3) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
7
作者：
Cho SW;Kim S;Kim Y;Kweon J;Kim HS;Bae S;Kim JS
通讯作者：
Kim JS
DOI：
10.1126/science.aaa5945
发表时间：
2015-04-24
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
Bier E
影响因子：
17.3
作者：
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通讯作者：
Barbas, Carlos F., III
影响因子：
46.9
作者：
Van Trung Chu;Weber, Timm;Kuehn, Ralf
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