Establishment and equilibrium levels of deleterious mutations in large populations
dc.contributor.author | Viljoen, Johan W. | |
dc.contributor.author | De Villiers, J Pieter. | |
dc.contributor.author | Van Zyl, Augustinus J. | |
dc.contributor.author | Mezzavilla, Massimo. | |
dc.contributor.author | Pepper, Michael Sean | |
dc.date.accessioned | 2020-08-28T11:16:56Z | |
dc.date.available | 2020-08-28T11:16:56Z | |
dc.date.issued | 2019-07 | |
dc.description.abstract | Analytical 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.department | Electrical, Electronic and Computer Engineering | en_ZA |
dc.description.department | Immunology | en_ZA |
dc.description.department | Mathematics and Applied Mathematics | en_ZA |
dc.description.librarian | pm2020 | en_ZA |
dc.description.uri | http://www.nature.com/srep/index.html | en_ZA |
dc.identifier.citation | Viljoen, 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.issn | 2045-2322 (online) | |
dc.identifier.other | 10.1038/s41598-019-46803-7 | |
dc.identifier.uri | http://hdl.handle.net/2263/75951 | |
dc.language.iso | en | en_ZA |
dc.publisher | Nature Research | en_ZA |
dc.rights | © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License. | en_ZA |
dc.subject | Computational models | en_ZA |
dc.subject | Experimental models of disease | en_ZA |
dc.title | Establishment and equilibrium levels of deleterious mutations in large populations | en_ZA |
dc.type | Article | en_ZA |