A lower prevalence for recessive disorders in a random mating population is a transient phenomenon during and after a growth phase

TL;DR

This study models how population growth and mating patterns influence the prevalence of recessive disorders, revealing transient decreases in disease incidence in expanding populations and persistent risks in consanguineous groups.

Contribution

The paper introduces a theoretical model analyzing mutation load and disease incidence dynamics during population growth and inbreeding, clarifying transient and long-term effects.

Findings

Recessive disorder prevalence drops during population expansion in random mating.

Mutation load increases in expanding populations with random mating.

Consanguineous populations maintain stable disease incidence levels.

Abstract

Despite increasing data from population-wide sequencing studies, the risk for recessive disorders in consanguineous partnerships is still heavily debated. An important aspect that has not sufficiently been investigated theoretically, is the influence of inbreeding on mutation load and incidence rates when the population sizes change. We therefore developed a model to study these dynamics for a wide range of growth and mating conditions. In the phase of population expansion and shortly afterwards, our simulations show that there is a drop of diseased individuals at the expense of an increasing mutation load for random mating, while both parameters remain almost constant in highly consanguineous partnerships. This explains the empirical observation in present times that a high degree of consanguinity is associated with an increased risk of autosomal recessive disorders. However, it also states that the higher frequency of severe recessive disorders with developmental delay in inbred populations is a transient phenomenon before a mutation-selection balance is reached again.