Population Dynamics of Tay-Sachs Disease. II. What Confers the Selective Advantage Upon the Jewish Heterozygote?

Abstract

It is now well established that the birth incidence of Tay-Sachs disease (TSD) is a hundred times higher, and the gene frequency ten times higher among Ashkenazi Jews than among other Jewish groups and non-Jewish populations (Goldschmidt et al., 1956, Kozinn et al., 1957, Myrianthopoulos, 1962, Aronson, 1964). The present authors (Myrianthopoulos and Aronson, 1966) examined several possible mechanisms but found no evidence that differential breeding pattern, genetic drift or differential mutation rate could explain the difference in gene frequency distribution. We then tested the possibility of differential fertility of the heterozygote for the TSD gene by comparing the reproductive performance of the grandparents of a large number of Jewish infants affected with TSD with that of an appropriate control group. The results suggested that the Jewish TSD heterozygote enjoys an overall reproductive advantage of about 6% over the presumed Jewish homozygous normal and that TSD sibships had significantly higher survival to age 21 than did control sibships. This advantage is of more than sufficient magnitude to have raised the frequency of the lethal TSD gene among the Ashkenazi Jews from a presumed frequency equal to that of non-Jews of 0.0013 at the end of the first century A.D. when the mass emigration of the Jews began, through 50 generations to the late 19th century, when TSD was recognized as occurring chiefly among Ashkenazi Jews with a gene frequency of 0.0126.