Murphy E A
Am J Med Genet. 1981;8(1):35-52. doi: 10.1002/ajmg.1320080106.
The notional principles of the genetics of disease are broadly discussed. Disease is an intrinsically vague term that represents the incongruity between the inner milieu of the organism and the environment. Its dynamics, then, cannot be reduced to naive statements about selection which may operate, and operate conflictingly, on several different levels or organization. Evolutionary selection results from the advantage of complexity, and the fundamental theorem of genetic dynamics - that mutational debts must eventually be paid in full-may be false or, at best approximate. The traditional models (mendelian, galtonian, and threshold) are set in a context that identifies certain features of disease that hitherto have been totally ignored. Neither invention nor traditional analysis has been adequate. Models should be made individually adequate for the study of diseases; the diseases should not be trimmed to fit the models.
本文广泛讨论了疾病遗传学的概念性原则。疾病是一个本质上模糊的术语，它代表了生物体内部环境与外部环境之间的不协调。因此，其动态变化不能简化为关于选择的简单陈述，因为选择可能在几个不同层次或组织上起作用，而且作用方式相互冲突。进化选择源于复杂性的优势，而遗传动力学的基本定理——突变债务最终必须全额偿还——可能是错误的，或者充其量只是近似正确的。传统模型（孟德尔模型、高尔顿模型和阈值模型）是在一种背景下建立的，这种背景确定了某些迄今为止完全被忽视的疾病特征。无论是发明还是传统分析都不够充分。模型应该针对疾病研究单独构建，而不是调整疾病去适应模型。
