Reproductive compensation and human genetic disease

Abstract

SummaryThe effects of reproductive compensation on the population genetics of sex-linked recessive lethal mutations are investigated. Simple equations are presented which describe these effects, and so complement existing population genetic theory. More importantly, this type of mutation is responsible for several severe human genetic diseases such as Duchenne muscular dystrophy. It is argued that the applications of three modern reproductive technologies -effective family planning, in utero diagnosis with termination, and embryo sexing -will lead to reproductive compensation. The adoption of any of these technologies may rapidly elevate the frequencies of those mutations which are lethal in childhood. This increase is large, in the order of 33 % upwards, and occurs rapidly over two to five generations. It also depends on the source of mutations, the effect being larger if most mutations are paternal. In utero diagnosis and\or embryo sexing increase the frequency of the mutation, but simultaneously decrease disease incidence by preventing the birth of affected offspring. In contrast, effective family planning may rapidly increase both mutation frequency and disease incidence.

Reproductive compensation in the evolution of plant mating systems

“…The concept of reproductive compensation is mainly used in human genetics (Hastings, 2000, 2001) and has been applied to some mammalian species (e.g. Charlesworth, 1994).…”

“…Numerous theoretical and empirical studies demonstrate that reproductive compensation can play a major role in the maintenance of deleterious mutations in mammal populations (Charlesworth, 1994; Hastings, 2001; Overall et al ., 2002). Despite this potential role in mating system evolution, reproductive compensation has received little attention from plant evolutionary biologists.…”

Male-killing Wolbachia in a live-bearing arthropod: Brood abortion as a constraint on the spread of a selfish microbe

“…In live-bearing hosts, reallocation of maternal resources from dead male embryos to their female siblings provides an additional, physiological mechanism through which kin selection could favor the evolution of male killing. In human and mammalian genetics, the term ''reproductive compensation'' is frequently used to denote a more restricted form of fitness compensation in which dead embryos are replaced by potentially viable ones (Charlesworth, 1994;Hastings, 2001). If females typically produce more embryos than they can carry to term and reproductive compensation occurs, an elevated rate of fetal mortality need not translate into a proportional decrease in the number of offspring born.…”

Effects of consanguinity on pre-reproductive mortality: Does demographic transition matter?

“…This hypothesis has been verified in populations that have limited their reproductive output according to the increased likelihood of having surviving offspring, but then replace children losses during infancy. If this loss is caused by a genetic disorder then the surviving replacement is more likely to be a carrier (2/3 of surviving offspring) than a noncarrier (1/3), hence maintaining the existence of the recessive mutation in the population (Hastings, 2000(Hastings, , 2001. Further studies in U.K. Asian communities have demonstrated that reproductive compensation can effectively counteract the purging of deleterious alleles within consanguineous populations (Overall et al, 2002).…”