Deaf intermarriage has limited effect on the prevalence of recessive deafness and no effect on underlying allelic frequency

Abstract

The idea that deaf intermarriage increases the prevalence of deafness was forcefully pushed in the late 19th century by Alexander Graham Bell, in proceedings published by the National Academy of Science. Bell’s hypothesis was not supported by a 19th century study by Edward Allen Fay, which was funded by Bell’s own organization, the Volta Bureau. The Fay study showed through an analysis of 4,471 deaf marriages that the chances of having deaf children did not increase significantly when both parents were deaf. In light of an apparent increase in non-complementary pairings when a modern dataset of Gallaudet alumni was compared with the 19th century Fay dataset, Bell’s argument has been resurrected. This hypothesis is that residential schools for the deaf, which concentrate signing deaf individuals together, have promoted assortative mating, which in turn has increased the prevalence of recessive deafness and also the commonest underlying deafness allele. Because this hypothesis persists, even though it contradicts classical models of assortative mating, it is critically important that it be thoroughly investigated. In this study, we used an established forward-time genetics simulator with parameters and measurements collected from the published literature. Compared to mathematical equations, simulations allowed for more complex modeling, operated without assumptions of parametricity, and captured ending distributions and variances. Our simulation results affirm predictions from classical equations and show that intense assortative mating only modestly increases the prevalence of deafness, with this effect mostly completed by the third generation. More importantly, our data show that even intense assortative mating does not affect the frequency of the underlying alleles under reported conditions. These results are not locus-specific and are generalizable to other forms of recessive deafness. We explain the higher rate of non-complementary pairings measured in the contemporary Gallaudet alumni sample as compared to the Fay dataset.

Agent-based modeling of DFNB1A prevalence with regard to intensity of selection pressure in isolated human population: will cochlear implantation increase the cases of hereditary deafness?

“…The copyright holder for this preprint this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.11.21261942 doi: medRxiv preprint 13 recessive mutant homozygotes to the next generation. A similar effect was observed in the study by Braun et al (2020), where the proportion of homozygotes increased by 23% (from 0.017% to 0.022%) while the frequency of recessive pathogenic allele did not change (an increase of only 0.002%) [30].…”

“…In a population in which HL is only due to recessive single-locus deafness (there are no other causes of HL), a couple of married deaf individuals will be able to have only deaf children, thereby making an increased contribution of the recessive mutant homozygotes to the next generation. A similar effect was observed in the study by Braun et al (2020), where the proportion of homozygotes increased by 23% (from 0.017% to 0.022%) while the frequency of recessive pathogenic allele did not change (an increase of only 0.002%) [30].…”

“…The copyright holder for this preprint this version posted August 13, 2021. ; https://doi.org/10.1101/2021.08.11.21261942 doi: medRxiv preprint 14 which resulted in a minimal increase in the proportion of mutant homozygotes (by ~1.5%) over 400 years [24]. Brown et al (2020) showed that in a model population with random mating, the frequency of the pathogenic allele and the proportion of mutant homozygotes did not change over 200 years (10 generations) [30].…”

“…Thus, the results of the modeling showed that in an isolated population with a low effective size and a high carrier frequency of pathogenic recessive allele the introduction of total cochlear implantation cannot lead to an increase in prevalence of hereditary HL (Figure 3). A similar "panmictic" scenario versus a scenario with assortative marriages by deafness were tested in two previous studies [24,30]. Nance & Kearsey (2004) modelled a population with a totally random choice of a partner (random mating) and the equal reproductive capabilities of deaf and hearing individuals, which resulted in a minimal increase in the proportion of mutant homozygotes (by ~1.5%) over 400 years [24].…”

“…Nance & Kearsey (2004) modelled a population with a totally random choice of a partner (random mating) and the equal reproductive capabilities of deaf and hearing individuals, which resulted in a minimal increase in the proportion of mutant homozygotes (by ~1.5%) over 400 years [24]. Brown et al (2020) showed that in a model population with random mating, the frequency of the pathogenic allele and the proportion of mutant homozygotes did not change over 200 years (10 generations) [30].…”