Impact on Jewish communities
Millions of Ashkenazi Jews have been screened as Tay-Sachs carriers since carrier testing began in 1971. Jewish communities, both inside and outside of Israel, embraced the cause of genetic screening from the 1970s on. Success with Tay-Sachs disease led Israel to become the first country to offer free genetic screening and counseling for all couples. Israel has become a leading center for research on genetic disease. Both the Jewish and Arab/Palestinian populations in Israel contain many ethnic and religious minority groups, and Israel's initial success with Tay-Sachs disease has led to the development of screening programs for other diseases. Israel's success with Tay-Sachs disease has also opened several discussions and debates about the proper scope of genetic testing for other disorders.
Much awareness of ''Ashkenazi Jews'' as an ethnic group stems from the large number of genetic studies of disease, including many that are well reported in the media, that have been conducted among Jews. The result is a form of ascertainment bias, in that many Jewish mutations have been discovered, and many disease associations have been reported in Jewish populations. According to Daphna Birenbaum Carmeli at the University of Haifa, Jewish populations have been studied more thoroughly than most other human populations, for a variety of reasons:
- Jewish populations, and particularly the large Ashkenazi Jewish population, are ideal for such research studies, because they exhibit a high degree of endogamy, yet they are sizable.
- Geneticists are intrinsically interested in Jewish populations, and a disproportionate percentage of genetics researchers are Jewish. Israel in particular has become an international center of such research.
- Jewish populations are overwhelmingly urban, and are concentrated near biomedical centers where such research has been carried out. Such research is especially easy to carry out in Israel, where cradle-to-grave medical insurance is available, together with universal screening for genetic disease.
- Jewish communities are comparatively well informed about genetics research, and have been supportive of community efforts to study and prevent genetic diseases.
- Participation of Jewish scientists and support from the Jewish community alleviates ethical concerns that sometimes hinder such genetic studies in other ethnic groups.
This has sometimes created an impression that Jews are more susceptible to genetic disease than other populations. Carmeli writes: "Jews are over-represented in human genetic literature, particularly in mutation-related contexts."
Jewish community institutions, flush with success in Tay-Sachs screening, aided these researchers, and extended genetic screening programs to cover new diseases. In a population already well-informed because of Tay-Sachs screening, publicity about breast cancer mutations helped researchers identify and recruit families with familial patterns of breast cancer for further study. As a result, the newly discovered BRCA1 and BRCA2 mutations became identified as "Jewish mutations," despite evidence that there are many such mutations at these loci, found in all populations, and that the particular founder mutations prevalent among Ashkenazi Jews also occur in other populations linked historically or geographically to Ashkenazi Jews. Sheila Rothman and Sherry Brandt-Rauf write: "Our findings cast doubt on the accuracy and desirability of linking ethnic groups to genetic disease. Such linkages exaggerate genetic differences among ethnic groups and lead to unequal access to testing and therapy." which emphasizes the role of genetic drift.
The controversy over heterozygote advantage and TSD began at a time, in the 1960s and 1970s, when all three of these debates were active. If a selective process favors carriers, then the prevalence of the classic TSD mutation in Ashkenazi Jews is a case of overdominance. With respect to the great debates among geneticists at large, this would be regarded as evidence for overdominance, for the balancing hypothesis, and for selectionism in general.
The classic case of heterozygote advantage in humans is sickle cell anemia, a disease for which carriers of several common mutations have greater resistance to malaria, an advantage in malarial environments. In the 1960s and 1970s, some researchers argued that there must be some evolutionary benefit to being a heterozygote for Tay-Sachs as well.
In the 1970s and 80s, several researchers investigated whether being a Tay-Sachs carrier might have served as a form of protection against tuberculosis in medieval Europe. Tuberculosis was prevalent in the European Jewish populations, in part because Jews were forced to live in crowded ghettos. However, several statistical studies have demonstrated that grandparents of Tay-Sachs carriers (who are more likely to have been carriers themselves) died proportionally from the same causes as non-carriers.
A more recent theory of heterozygote advantage (attributed to Gregory Cochran) proposes that Tay-Sachs, and the other lipid storage diseases that are prevalent in Ashkenazi Jews, reflect genes that enhance dendrite growth and promote higher intelligence when present in carrier form. In this way, Cochran proposes that being a heterozygote provided a selective advantage at a time when Ashkenazi Jews were restricted to intellectual occupations. (See Ashkenazi intelligence theory.)
Researchers of the 1960s and 1970s often favored theories of overdominance as an explanation of heterozygote advantage, but failed to find much evidence for them in human populations. They were also unaware of the diversity of the Tay-Sachs mutation base. In the 1970s, complete genomes had not yet been sequenced, and researchers were unaware of the extent of polymorphism. The contribution to evolution of genetic drift (as opposed to natural selection) was not fully appreciated.
Since the 1970s, DNA sequencing techniques using PCR have been applied to many genetic disorders, and in other human populations. Several broad genetic studies of the Ashkenazi population (not related to genetic disease) have demonstrated that the Ashkenazi Jews are the descendants of a small founder population, which may have gone through additional population bottlenecks. These studies also correlate well with historical information about Ashkenazi Jews. Thus, a preponderance of the recent studies have supported the /b>founder effects theory.
This emerging consensus in favor of genetic drift reflects broader trends in genetics. Among current researchers in medical genetics, interest in overdominance as an explanation for heterozygote advantage has waned. Overdominance in particular and balancing selection in general are now regarded as unusual phenomena, and the classic cases (such as sickle cell anemia) are regarded as exceptions to the rule. According to James F. Crow, Kimura's neutral theory of molecular evolution and its successors largely sidestepped the classical/balance debate among population geneticists, by shifting the focus of debate to the molecular level, where genetic drift could be confirmed with empirical evidence. In another review article, Crow notes that dominance has become accepted among applied geneticists as the best explanation for heterosis.
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