Viljoen, Johan W.De Villiers, J Pieter.Van Zyl, Augustinus J.Mezzavilla, Massimo.Pepper, Michael Sean2020-08-282020-08-282019-07Viljoen, J.W., De Villiers, J.P., Van Zyl, A.J. et al. 2019,'Establishment and equilibrium levels of deleterious mutations in large populations', Scientific Reports, vol. 9, no. 1, art. 10384, pp. 1-10.2045-2322 (online)10.1038/s41598-019-46803-7http://hdl.handle.net/2263/75951Analytical and statistical stochastic approaches are used to model the dispersion of monogenic variants through large populations. These approaches are used to quantify the magnitude of the selective advantage of a monogenic heterozygous variant in the presence of a homozygous disadvantage. Dunbar’s results regarding the cognitive upper limit of the number of stable social relationships that humans can maintain are used to determine a realistic effective community size from which an individual can select mates. By envisaging human community structure as a network where social proximity rather than physical geography predominates, a significant simplification is achieved, implicitly accounting for the effects of migration and consanguinity, and with population structure and genetic drift becoming emergent features of the model. Effective community size has a dramatic effect on the probability of establishing beneficial alleles. It also affects the eventual equilibrium values that are reached in the case of variants conferring a heterozygous selective advantage, but a homozygous disadvantage, as in the case of cystic fibrosis and sickle cell disease. The magnitude of this selective advantage can then be estimated based on observed occurrence levels of a specific allele in a population, without requiring prior information regarding its phenotypic manifestation.en© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License.Computational modelsExperimental models of diseaseArticle