Tay-Sachs disease and the role of reproductive compensation in the maintenance of ethnic variations in the incidence of autosomal recessive disease

Summary Several deleterious and lethal autosomal recessive genes appear to exist in equilibrium with their normal alleles at a variety of stable, or near stable frequencies of considerable antiquity. One person in 25 is, for instance, a carrier of the Tay-Sachs gene among Ashkenazi Jews, compared with 1 in 300 among Sephardic and Oriental Jews and non-Jews. The explanations offered for t his phenomenon have generally not been entirely satisfactory. It has been shown that parents replace fortuitous infant and childhood deaths with, on average, approximately two surviving sibs each. When mutation rates are low, this practice, which has also been shown to occur among other animals, can maintain considerable variations in the stable incidence of autosomal recessive disease, should such ethnic polymorphism arise through genetic drift, the founder effect or hitch-hiking. High mutation rates would appear to preclude ethnic variations in the stable incidence of genetic disease.