Gibson Greg, Lacek Kristine A
School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia 30332, USA; email:
Annu Rev Genet. 2020 Nov 23;54:189-211. doi: 10.1146/annurev-genet-022020-022327. Epub 2020 Aug 31.
Canalization refers to the evolution of populations such that the number of individuals who deviate from the optimum trait, or experience disease, is minimized. In the presence of rapid cultural, environmental, or genetic change, the reverse process of decanalization may contribute to observed increases in disease prevalence. This review starts by defining relevant concepts, drawing distinctions between the canalization of populations and robustness of individuals. It then considers evidence pertaining to three continuous traits and six domains of disease. In each case, existing genetic evidence for genotype-by-environment interactions is insufficient to support a strong inference of decanalization, but we argue that the advent of genome-wide polygenic risk assessment now makes an empirical evaluation of the role of canalization in preventing disease possible. Finally, the contributions of both rare and common variants to congenital abnormality and adult onset disease are considered in light of a new kerplunk model of genetic effects.
表型整合是指种群的进化，使得偏离最优性状或患疾病的个体数量降至最低。在文化、环境或基因快速变化的情况下，去整合化这一相反过程可能导致观察到的疾病患病率上升。本综述首先定义相关概念，区分种群的表型整合和个体的稳健性。然后考虑与三个连续性状和六个疾病领域相关的证据。在每种情况下，关于基因-环境相互作用的现有遗传证据不足以有力推断去整合化，但我们认为全基因组多基因风险评估的出现现在使得对表型整合在预防疾病中的作用进行实证评估成为可能。最后，根据一种新的基因效应“突然失败”模型，考虑罕见和常见变异对先天性异常和成人发病疾病的影响。
