Establishment and equilibrium levels of deleterious mutations in large populations

dc.contributor.authorViljoen, Johan W.
dc.contributor.authorDe Villiers, J Pieter.
dc.contributor.authorVan Zyl, Augustinus J.
dc.contributor.authorMezzavilla, Massimo.
dc.contributor.authorPepper, Michael Sean
dc.date.accessioned2020-08-28T11:16:56Z
dc.date.available2020-08-28T11:16:56Z
dc.date.issued2019-07
dc.description.abstractAnalytical 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_ZA
dc.description.departmentElectrical, Electronic and Computer Engineeringen_ZA
dc.description.departmentImmunologyen_ZA
dc.description.departmentMathematics and Applied Mathematicsen_ZA
dc.description.librarianpm2020en_ZA
dc.description.urihttp://www.nature.com/srep/index.htmlen_ZA
dc.identifier.citationViljoen, 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.en_ZA
dc.identifier.issn2045-2322 (online)
dc.identifier.other10.1038/s41598-019-46803-7
dc.identifier.urihttp://hdl.handle.net/2263/75951
dc.language.isoenen_ZA
dc.publisherNature Researchen_ZA
dc.rights© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License.en_ZA
dc.subjectComputational modelsen_ZA
dc.subjectExperimental models of diseaseen_ZA
dc.titleEstablishment and equilibrium levels of deleterious mutations in large populationsen_ZA
dc.typeArticleen_ZA

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