Lindex #0148

Myrianthopoulos NC, Aronson SM

Population Dynamics of Tay-Sachs Disease I. Reproductive Fitness and Selection

American Journal of Human Genetics

1966; 18:313-327

The authors reported the results of a study among whose purposes was to examine the mechanisms by which the lethal gene for Tay-Sachs disease becomes elevated and maintained and to suggest one possible responsible mechanism. The authors suggest that the following mechanisms may be involved: differential breeding pattern, genetic drift, differential mutation rate, differential fertility of the heterozygote and a combination of any of the above. The data upon which the study was based was derived from two sources. The first was the result of a screening of death certificates from the Bureau of Vital Statistics classified under the rubric "mental deficiency, and other unspecified types," for deaths occurring in the United States between 1954 and 1957. The second source of data was a case registry of cerebral sphingolipidoses begun in 1952. Eighty-nine cases of Tay-Sachs disease were derived from among the death certificates. Fifty-eight of these cases involved Jewish parents, 29 derived from non-Jewish parents and two cases involved parents of mixed parents. The registry provided 296 cases in 242 families, 226 of whom were in children of Jewish parents, 35 in children of non-Jewish parents, and 35 in children with mixed or doubtful parentage. Complete data was gathered from 194 families of Jewish cases and 47 families of non-Jewish cases. Data concerned with the 388 Jewish sibship with 1,244 siblings and control sibships comprised of couples whose children did not have Tay-Sachs disease. In addition the control sample reflected the Tay-Sachs sample in terms of the urban and suburban Jewish population of the northeastern United States as well as country of birth, age, number of children, religious-cultural background, socioeconomic level and geographic distribution. Data from among those in the control group was gathered from 406 couples comprising 812 sibships with 2,848 total siblings.

Data gathered by the authors failed to demonstrate differential breeding patterns, genetic drift or mutation rate as explanations for differences in the distribution of gene frequencies. On the other hand, the reproductive performance of grandparents of Jewish infants with Tay-Sachs disease compared with appropriate controls, demonstrates that the Jewish heterozygote enjoys an over-all reproductive advantage of about 6 percent over the presumed homozygous normal. The distribution it should be noted are not statistically significant. This reproductive advantage is most pronounced among offspring from outside of the United States who survive to reproduction age. On the other hand, the reproductive age, becoming negligible when total offspring born in the United States is considered. Tay-Sachs disease sibships are significantly more likely to survive to age 21 than control sibships lending further evidence to the heterozygote advantage hypothesis.