Societal and cultural aspects of Tay–Sachs disease explained

Advances in knowledge about Tay–Sachs disease have stimulated debate about the proper scope of genetic testing, and the accuracy of characterizing diseases as specific to one ethnicity. Jewish communities have been in the forefront of genetic screening and counseling for this disease.__TOC__

Impact on Jewish communities

Ashkenazi Jews have been screened as Tay–Sachs carriers since carrier testing began in 1971. Since the 1970s, many Jewish communities have embraced genetic screening, and in 1971, Israel became the first country to offer free genetic screening^[1] and counseling for Tay–Sachs disease and other diseases, leading to international discussion about the proper scope of genetic testing.^[2]

Much awareness of Ashkenazi Jews as an ethnic group stems from genetic studies of disease. Some regard these studies as exhibiting ascertainment bias^[3] which created an impression that Jews are more susceptible to genetic disease than other populations.^[4] They cite BRCA1 and BRCA2 mutations becoming identified as "Jewish mutations," despite there being mutations at these loci found in all populations. 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."^[4]

Controversy over heterozygote advantage

Genetic and historical studies of the Ashkenazi population suggest it may have gone through population bottlenecks, thereby giving strong support to the founder effects theory.^{[5] [6] [7] [8] [9]} Because Tay–Sachs disease was one of the first autosomal recessive genetic disorders for which there was a test, it was intensely studied as a model for all such diseases, and researchers sought evidence of a selective process through a selective advantage for heterozygotes (carriers). Neil Risch writes: "The anomalous presence of four different lysosomal storage disorders in the Ashkenazi Jewish population has been the source of long-standing controversy. Many have argued that the low likelihood of four such diseases — particularly when four are involved in the storage of glycosphingolipids — must reflect past selective advantage for heterozygous carriers of these conditions."^[5] Risch, an eminent statistical geneticist, believes the weight of evidence supports genetic drift, not a selective process.^[5]

Gregory Cochran proposes that the mutant alleles causing Tay–Sachs confer higher intelligence when present in carrier form, and provided a selective advantage in the historical period when Jews were restricted to intellectual occupations.^{[10] [11]}

Notes and References

1. Zlotogora. Joël. Grotto. Itamar. Kaliner. Ehud. Gamzu. Ronni. February 2016. The Israeli national population program of genetic carrier screening for reproductive purposes. Genetics in Medicine. en. 18. 2. 203–206. 10.1038/gim.2015.55. 25880436 . 19919680 . 1530-0366. free.
2. Ethical aspects of genetic screening in Israel . M . Sagi . Science in Context . 1998 . 11 . 419–429 . 15168671 . 3–4 . 10.1017/s0269889700003112. 31003675 .
3. Carmeli, Daphna Birenbaum. American Journal of Medical Genetics. 2004-08-04. Prevalence of Jews as subjects in genetic research: Figures, explanation, and potential implications. 130A. 1 . 76–83 . 15368499. 10.1002/ajmg.a.20291. 23251307.
4. Brandt-Rauf SI, Raveis VH, Drummond NF, Conte JA, Rothman SM . Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease . American Journal of Public Health . November 2006 . 96 . 11 . 1979–1988 . 17018815 . 1751808 . 10.2105/AJPH.2005.083014 .
5. Risch N, Tang H, Katzenstein H, Ekstein J . 2003. Geographic Distribution of Disease Mutations in the Ashkenazi Jewish Population Supports Genetic Drift over Selection. American Journal of Human Genetics. 72. 4. 812–822 . 12612865. 10.1086/373882 . 1180346.
6. Frisch A, Colombo R, Michaelovsky E, Karpati M, Goldman B, Peleg L . Origin and spread of the 1278insTATC mutation causing Tay–Sachs disease in Ashkenazi Jews: genetic drift as a robust and parsimonious hypothesis . Human Genetics . 2004 . 366–76 . 114 . 4 . 14727180 . 10.1007/s00439-003-1072-8. 10768286 .
7. Slatkin, M . 2004 . A Population-Genetic Test of Founder Effects and Implications for Ashkenazi Jewish Diseases. American Journal of Human Genetics. 75. 2. 282–293 . 15208782 . 10.1086/423146. 1216062.
8. Crow. James F. . James F. Crow. 2008 . Mid-Century Controversies in Population Genetics . Annual Review of Genetics . 42 . 1–16 . 18652542 . 10.1146/annurev.genet.42.110807.091612. free .
9. Crow . James F. . James F. Crow. 1997 . Motoo Kimura, 13 November 1924 - 13 November 1994 . Biographical Memoirs of Fellows of the Royal Society . 43 . 254–265 . 10.1098/rsbm.1997.0014. 11619978 . 44725944 .
10. Book: Gregory . Cochran . Gregory Cochran . Henry . Harpending . Henry Harpending . The 10,000 Year Explosion . 2009 . Basic Books . New York. Medieval Evolution: How the Ashkenazi Jews Got Their Smarts.
11. News: Researchers Say Intelligence and Diseases May Be Linked in Ashkenazic Genes . New York Times . 2005-06-03 . 2009-05-27 . Nicholas . Wade . Nicholas Wade .