Viljoen, J.Wde Villiers, J.Pvan Zyl, A.JMezzavilla, MPepper, M.S2024-06-092024-06-092019-07-17Viljoen JW, de Villiers JP, van Zyl AJ, Mezzavilla M, Pepper MS. Establishment and equilibrium levels of deleterious mutations in large populations. Scientific Reports. 2019;9(1):10384. DOI: 10.1038/s41598-019-46803-7.https://doi.org/10.1038/s41598-019-46803-7https://www.nature.com/articles/s41598-019-46803-7https://hdl.handle.net/11288/596525Analytical 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.enAttribution 3.0 United Stateshttp://creativecommons.org/licenses/by/3.0/us/MutationsDNA sequence of an organismLarge populationsArticleScientific Reports