The multifactorial/threshold concept -- uses and misuses.
The multifactorial/threshold concept -- uses and misuses.
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多因素/阈值概念——使用和误用。
DOI：
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发表时间：
1976
期刊：
影响因子：
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通讯作者：
F. Fraser
中科院分区：
文献类型：
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作者：
F. Fraser
常见的先天性畸形有家族分布，不能用简单的孟德尔模型来解释，但可以用一个连续变量来解释，即“责任”，有一个阈值，超过这个阈值，个体就会受到影响。遗传和环境因素都决定了责任，使该系统成为多因素系统。腭裂是一个有用的实验模型，说明了一些因素，有助于腭闭合，发育阈值的性质，以及基因和致畸剂如何改变的组成部分，增加腭裂的可能性。人类畸形的遗传因素的性质尚不清楚，从严格意义上的多基因到一个主要基因的遗传率降低的各种可能性都与数据相符，但重要的特征是阈值。对这一概念的混淆主要是由于术语的使用不一致。“多因素”一词应用于“由遗传和环境因素共同决定”，而不提及遗传因素的性质。“多基因”应该保留给“大量的基因，每个基因都有一个小的影响，起着累加作用。当涉及多个基因，具有更大的影响时，可以使用“多局部”。当不清楚哪一个适用时，建议使用“多域”一词，意思是“遗传变异比简单的孟德尔差异更复杂。“由于致畸数据往往代表阈值字符的概念也有重要的影响，解释数据的剂量-反应曲线，协同作用，应变差异，以应对致畸剂。
The common congenital malformations have familial distributions that cannot be accounted for by simple Mendelian models, but can be explained in terms of a continuous variable, "liability," with a threshold value beyond which individuals will be affected. Both genetic and environmental factors determine liability, making the system multifactorial. Cleft palate is a useful experimental model, illustrating a number of factors that contribute to palate closure, the nature of a developmental threshold, and how genes and teratogens can alter the components of liability to increase the probability of cleft palate. The nature of the genetic component to liability in human malformations in not clear, and various possibilities, ranging from polygenic in the strict sense to a major gene with reduced penetrance are compatible with the data -- but the important feature is the threshold. Much of the confusion over the concept results from inconsistent use of terminology. The term "multifactorial" should be used for "determined by a combination of genetic and environmental factors," without reference to the nature of the genetic factor(s). "Polygenic" should be reserved for "a large number of genes, each with a small effect, acting additively." When several genes, with more major effects are involved, "multilocal" can be used. When it is not clear which of these is applicable the term "plurilocal" is suggested, in the sense of "genetic variation more complex than a simple Mendelian difference." Since teratological data often represent threshold characters the concept also has important implications for the interpretation of data on dose-response curves, synergisms, and strain differences in response to teratogens.