Lindex #0891

Myrianthopoulos NC, Aronson SM

Population Dynamics of Tay-Sachs Disease. II. What Confers the Selective Advantage Upon the Jewish Heterozygote? in Volk, B.W. and Stanley M. Aronson (eds.).

Sphingolipids, Sphingolipidoses and Allied Disorders

New York: Plenum Press, 561-570

The authors examined the possible mechanisms for the selective advantage of the Jewish heterozygote for Tay-Sachs Disease (TSD). It has been well established that the birth incidence of TSD is 100 times higher and the gene frequency 10 times higher among Ashkenazi Jews than among other Jews or non-Jews. The authors found no evidence that differential breeding pattern, genetic drift or differential mutation rate could explain the difference in gene frequency distribution. The Jewish TSD heterozygote enjoys an overall reproductive advantage of about 6 percent over the presumed Jewish homozygous normal and TSD sibships had significantly higher survival to age 21 than controls. This advantage had raised the frequency of the lethal TSD gene among the Ashkenazi Jews from 0.0013 at the end of the First Century A.D. to 0.0126 in the late 19th century.

It has been shown that the greater proportion of antecedents of TSD cases in the United States came from the provinces bordering on the Baltic Sea, southern Lithuania, Suwalki and Grodno. The most frequent natural causes of death among the parents and grandparents of the TSD cases were cardiovascular and cerebrovascular diseases, followed by cancer, diabetes and respiratory infections. What was surprising was the virtual absence of deaths due to Tuberculosis (TBC), a disease quite prevalent in northeastern Europe. These data prompted the authors to test the hypothesis of TSD heterozygote resistance to TBC. They compared the distribution of places of origin of the TSD grandparents with that of patients with pulmonary TBC who also derived from eastern Europe.

The authors analyzed 1,466 medical records at the American Medical Center at Denver which served as a sanatorium for Jewish patients suffering from pulmonary TBC. There were There were 618 grandparents, 1,466 TBC patients and 1,675 controls. The data were grouped into three major geographic regions: Northern, Central and Southern. The data indicated that TBC was three times higher in the Southern region where the TSD frequency was the lowest, than in the Northern region where the TSD frequency was the highest. These result were consistent with the hypothesis of resistance to TBC on the part of the Jewish TSD carrier.

While the TSD incidence in American or Israeli descendants of Northern Polish-Russian Jews is relatively high, TSD was not high in Jewish children born in these regions. One investigator commented on this discrepancy, that it seemed as though the disease waited until the carriers emigrated to America or England before appearing. Another investigator proposed that the proportion of TSD carriers in the emigrating Jewish populations was higher than the proportion among those who did not emigrate. This explanation was in line with the hypothesis of carrier resistance to TBC.