Wolf U
Institut für Humangenetik und Anthropologie, Universität Freiburg, Germany.
Hum Genet. 1995 Feb;95(2):127-48. doi: 10.1007/BF00209392.
The phenotype is the result of ontogenetic development. This holds true also at the molecular level, because molecular biological processes take place within the organism. In ontogenesis, genetic and nongenetic factors interact in producing successive states, each of which is the prerequisite, and determines the conditions, for the next one to follow. In this interplay, genes are a necessary, but not sufficient, component. The structures already present, gradients, threshold values, positional relationships, and conditions of the internal milieu, are equally essential. Thus, even monofactorial traits can be considered to be of multifactorial causation, and the varying borderline conditions that arise during development add to the complexity. From this standpoint, it is not to be expected that a mutation has a consistent phenotypic outcome, and the genotype-phenotype relationship may be irregular. In the present review, genotypic heterogeneity versus phenotypic heterogeneity is discussed with the help of some selected examples of hereditary diseases. Conditions and mechanisms contributing to this heterogeneity are addressed. It is concluded that the genotype-phenotype relationship is neither unidimensional, programmatical nor hierarchical in a strict sense. Nevertheless, in particular cases, ontogenetic modification appears to be of minor significance, so that the phenotype of a mutation can be predicted with considerable accuracy. This is no surprise if, depending on the nature of the mutation and the physiological function of the gene affected, the genotype-phenotype relationship is direct. However, this relationship may also be consistent in more complex conditions. It is assumed that the total of the non-genetic influences (epigenetic, environmental) are usually so similar or are compensated by the organism to such an extent that the respective mutation acts as the major variable during ontogenetic development.
表型是个体发育的结果。这在分子水平上同样成立，因为分子生物学过程发生在生物体内部。在个体发育过程中，遗传和非遗传因素相互作用，产生连续的状态，每一种状态都是下一个状态的前提条件，并决定其条件。在这种相互作用中，基因是必要但不充分的组成部分。已经存在的结构、梯度、阈值、位置关系以及内部环境条件同样至关重要。因此，即使是单基因性状也可被认为是多因素导致的，发育过程中出现的各种边界条件增加了复杂性。从这个角度来看，不能期望一个突变具有一致的表型结果，基因型与表型的关系可能是不规则的。在本综述中，借助一些遗传性疾病的选定实例讨论了基因型异质性与表型异质性。探讨了导致这种异质性的条件和机制。得出的结论是，基因型与表型的关系在严格意义上既不是一维的、程序性的，也不是层级性的。然而，在特定情况下，个体发育修饰似乎意义不大，因此可以相当准确地预测突变的表型。如果根据突变的性质和受影响基因的生理功能，基因型与表型的关系是直接的，这并不奇怪。然而，在更复杂的情况下，这种关系也可能是一致的。据推测，非遗传影响（表观遗传、环境）的总和通常非常相似，或者被生物体补偿到这样的程度，以至于各自的突变在个体发育过程中成为主要变量。
