Why genetic selection to reduce the prevalence of infectious diseases is way more promising than currently believed.
Why genetic selection to reduce the prevalence of infectious diseases is way more promising than currently believed.
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DOI：
10.1093/genetics/iyab024
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发表时间：
2021-04-15
期刊：
影响因子：
3.3
通讯作者：
Bijma P
中科院分区：
文献类型：
--
作者：
Hulst AD;de Jong MCM;Bijma P
提高抗病性的遗传选择是农业中防治传染病策略的重要组成部分。然而，二元疾病状态的定量遗传分析表明，大多数疾病的遗传力较低，这限制了疾病患病率的遗传降低率。此外，共同责任阈值模型表明，通过基因选择消除传染病是不可能的，因为当流行率接近零时，观察到的规模遗传力也为零。然而，从传染病流行病学来看，我们知道消灭传染病在理论上和实践上都是可能的，因为正反馈机制会导致群体免疫现象。然而，常见的定量遗传模型忽略了这些反馈机制。在这里，我们将二元疾病状态的定量遗传分析与传播流行病学模型相结合，旨在确定对减少地方性传染病患病率的选择的潜在反应。结果表明，二元疾病状态的典型遗传力值对应于个体之间疾病易感性的非常显着的遗传变异。此外，我们的结果表明，通过基因选择消除传染病原则上是可能的。这些发现与基于常见定量遗传模型的预测强烈不同，该模型忽略了减少传染病传播时发生的正反馈效应。这些反馈效应是一种特殊的间接遗传效应；它们对选择反应和群体免疫的发展（即有效繁殖率小于一）做出了重大贡献。
Genetic selection for improved disease resistance is an important part of strategies to combat infectious diseases in agriculture. Quantitative genetic analyses of binary disease status, however, indicate low heritability for most diseases, which restricts the rate of genetic reduction in disease prevalence. Moreover, the common liability threshold model suggests that eradication of an infectious disease via genetic selection is impossible because the observed-scale heritability goes to zero when the prevalence approaches zero. From infectious disease epidemiology, however, we know that eradication of infectious diseases is possible, both in theory and practice, because of positive feedback mechanisms leading to the phenomenon known as herd immunity. The common quantitative genetic models, however, ignore these feedback mechanisms. Here, we integrate quantitative genetic analysis of binary disease status with epidemiological models of transmission, aiming to identify the potential response to selection for reducing the prevalence of endemic infectious diseases. The results show that typical heritability values of binary disease status correspond to a very substantial genetic variation in disease susceptibility among individuals. Moreover, our results show that eradication of infectious diseases by genetic selection is possible in principle. These findings strongly disagree with predictions based on common quantitative genetic models, which ignore the positive feedback effects that occur when reducing the transmission of infectious diseases. Those feedback effects are a specific kind of Indirect Genetic Effects; they contribute substantially to the response to selection and the development of herd immunity (i.e., an effective reproduction ratio less than one).
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
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通讯作者：
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