Canalization and Robustness in Human Genetics and Disease.
Annu Rev Genet
; 54: 189-211, 2020 11 23.
Article
em En
| MEDLINE
| ID: mdl-32867542
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genoma
/
Genética Humana
/
Doenças Genéticas Inatas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Annu Rev Genet
Ano de publicação:
2020
Tipo de documento:
Article