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Agent-Based Modeling of Autosomal Recessive Deafness 1A (DFNB1A) Prevalence with Regard to Intensity of Selection Pressure in Isolated Human Population.

Georgii P RomanovAnna A SmirnovaVladimir I ZamyatinAleksei M MukhinFedor V KazantsevVera G PshennikovaFedor M TeryutinAisen V SolovyevSardana A FedorovaOlga L PosukhSergey A LashinNikolay A Barashkov
Published in: Biology (2022)
An increase in the prevalence of autosomal recessive deafness 1A (DFNB1A) in populations of European descent was shown to be promoted by assortative marriages among deaf people. Assortative marriages became possible with the widespread introduction of sign language, resulting in increased genetic fitness of deaf individuals and, thereby, relaxing selection against deafness. However, the effect of this phenomenon was not previously studied in populations with different genetic structures. We developed an agent-based computer model for the analysis of the spread of DFNB1A. Using this model, we tested the impact of different intensities of selection pressure against deafness in an isolated human population over 400 years. Modeling of the "purifying" selection pressure on deafness ("No deaf mating" scenario) resulted in a decrease in the proportion of deaf individuals and the pathogenic allele frequency. Modeling of the "relaxed" selection ("Assortative mating" scenario) resulted in an increase in the proportion of deaf individuals in the first four generations, which then quickly plateaued with a subsequent decline and a decrease in the pathogenic allele frequency. The results of neutral selection pressure modeling ("Random mating" scenario) showed no significant changes in the proportion of deaf individuals or the pathogenic allele frequency after 400 years.
Keyphrases
  • endothelial cells
  • risk factors
  • intellectual disability
  • genome wide
  • autism spectrum disorder
  • gene expression
  • pluripotent stem cells
  • deep learning
  • dna methylation
  • genetic diversity