Population dynamics of Tay-Sachs disease. I. Reproductive fitness and selection.

TAY-SACHS DISEASE (TSD) or infantile amaurotic familial idiocy is a hereditary disease of lipid storage in which the sphingolipid ganglioside accumulates in the cytoplasm of the neurons of the brain. It is characterized by progressive degeneration of cerebral function which commences soon after birth and ends in death usually within the first or second year of life. The disease has been demonstrated to be due to the homozygous condition of an autosomal recessive gene, apparently with complete penetrance (Slome, 1933; Ktenides, 1954; Kozinn, Wiener, and Cohen, 1957; Aronson, Aronson, and Volk, 1959). When the disease was first recognized, it was thought to be an exclusively Jewish disorder, but verified cases in non-Jewish infants were reported later. These cases have become increasingly numerous in the literature in recent years, and Myrianthopoulos (1962) showed that fully one-third of cases in the United States are of non-Jewish origin. It is further well established that TSD is more frequent among the Ashkenazi Jews than among other Jewish (Sephardi) groups and non-Tewish populations. (See above investigators as well as Goldschmidt et al., 1956; Goldschmidt, Ronen, and Ronen, 1960; Goldschmidt and Cohen, 1964). Although considerable literature has recently been devoted to the genetics, epidemiology, and demography of the disease, the major problem of why the TSD gene, despite its mass elimination, is found in such high frequency among the Ashkenazi Jews is still unresolved. The purpose of this paper is to examine the mechanisms by which the frequency of so lethal a gene could have become elevated and then maintained at the present high level and to present evidence which suggests that one such mechanism may have been responsible for this phenomenon. Estimates of the frequency of the TSD gene among Tews and among nonTews are in rather close agreement (Table 1). In the United States, the disease occurs once in approximately 6,000 Jewish births and once in approximately 500,000 non-Tewish births. On the basis of this birth incidence, it is estimated that one of 40 Jewish persons and one of 380 non-Jewish persons is heterozy-