Department of Electrical, Electronic and Computer Engineering, EBIT, University of Pretoria, Pretoria, 0028, South Africa.
Development, Research and Technology Department, Hensoldt Optronics, Centurion, 0157, South Africa.
Sci Rep. 2019 Jul 17;9(1):10384. doi: 10.1038/s41598-019-46803-7.
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.
分析和统计随机方法被用于通过大群体来模拟单基因变异的离散性。这些方法用于量化在存在纯合劣势的情况下，单基因杂合变体的选择优势的大小。邓巴关于人类可以维持的稳定社交关系数量的认知上限的研究结果被用来确定一个现实的有效社区规模，个体可以从该社区中选择配偶。通过将人类社区结构设想为一个网络，其中社交关系而非物理地理占据主导地位，实现了显著的简化，隐含地考虑了迁移和血缘关系的影响，并且人口结构和遗传漂变成为模型的新兴特征。有效社区规模对建立有益等位基因的概率有巨大影响。它还会影响在赋予杂合选择优势但纯合劣势的情况下变体最终达到的平衡值，例如囊性纤维化和镰状细胞病。然后，可以根据在特定人群中特定等位基因的观察发生水平来估计这种选择优势的大小，而无需事先了解其表型表现的信息。
