Wednesday, June 17, 2009

Tay-Sachs disease in Ashkenazi Jews: Origins and Preventions

Tay-Sachs disease is an autosomal recessive disease which is fatal in its most common form, known as infantile Tay-Sachs. It is known to have a high prevalence in Ashkenazi Jews. In this essay I am going to explain how the high prevalence of the mutation could have originated in the Jewish population and how the disease can be prevented.

Approximately 1 in 25 Ashkenazi Jews are carriers of Tay-Sachs disease which makes this population particularly susceptible. Only 1 in 250 people are carriers in the general population. Although Ashkenazi Jews are more susceptible to many other diseases Tay-Sachs is a particularly terrible disease as it leaves a child blind, deaf and unable to swallow. Babies with Tay-Sachs are born without Hexosaminidase A which would otherwise clear out unwanted fatty proteins which interfere with baby’s sight, hearing, movement and mental development.

It is not known for definite as to why this population has a high carrier rate but there are some very strong explanations. The first theory I found involves the infectious disease tuberculosis. From some evidence it appears that Tay-Sachs provides some protection against TB, and it is this that may explain why Ashkenazi Jews have a high carrier rate. When World War 2 broke out TB spread through the eastern European Jewish settlements. This was particularly dangerous because these Jews were prevented from moving out of the ghettos that they were forced to live in by the Nazis. However, healthy parents who had children with Tay-Sachs disease did not contact TB, even though they were sometimes repeatedly exposed. The parents must have been carriers of Tay-Sachs in order to have children with the disease, since it is an autosomal recessive infliction. Therefore being a carrier of Tay-Sachs seems to have provided some sort of protection against TB, although why it provides protection is not so clear and is still not fully known.

To relate this idea to evolution, the Ashkenazi Jews at the time were exposed to a serious epidemic of TB in their area, so many people who were not carriers would have contacted TB and died meaning they would not raise offspring in the future. On the other hand individuals with the allele for Tay-Sachs would not have contacted TB and passed on their genes to their offspring. It is an example of survival of the fittest (natural selection) so even though Tay-Sachs is a dangerous disease, at the time of world war 2 many people without the allele for the disease were wiped out by TB making the allele more prevalent in the population.

Genetic drift is another theory as to why Ashkenazi Jews have a higher carrier frequency of Tay-Sachs. Genetic drift is the random fluctuations of frequencies of the appearance of genes in an isolated population. It relies on the fact that alleles of offspring are a random sample of those of their parents, and one allele can become more prevalent in a population by chance. As I have already described the Ashkenazi Jews were isolated in ghettos by the Nazis which is why they were susceptible to genetic drift. The effect of genetic drift is much larger in smaller populations which is why it doesn’t usually play a large role in allele frequency for the general population. Using this theory, it is possible the Tay-Sachs is prevalent in Ashkenazi Jews just through a random process. The fact that there was a small population involved meant that it was easier for one allele to become more prevalent than another allele. Genetic drift would have also played a role in making the prevalence of the Tay-Sachs allele high in the population even if the Ashkenazi Jews were not forced to stay in ghettoes. This is because the population of Ashkenazi Jews was small in the first place, and a small population would allow genetic drift to be more effective. Natural selection would not have caused the allele to become prevalent without the effect of TB because natural selection only allows alleles giving an advantage to be passed on to offspring, which is why genetic drift is a strong theory.

The last theory is the founder effect which occurs when a population is started from a very small number of individuals. It believed the Ashkenazi Jew population was started from only a few thousand individuals who lived in Eastern Europe, and millions of people can now trace their ancestry to this population. Therefore even if a small number of people in the founding population are carriers of the mutation, the defect would become amplified over time and so when the population reaches high numbers, there will be a large number of people with the defect. This theory would need to rely on the chance presence of certain mutations in the founders of today’s Ashkenazi Jewish population.

At the moment there is no cure for Tay-Sachs disease. We can only try and prevent more cases from occurring, and this is done through screening for potential carriers of the disease. This is especially important if the future parents have both high risk ethnic origins such as both being Ashkenazi Jews. The potential parents both have genetic tests done to see if they are carriers or not, so they can be warned about the dangers of starting a family. Genetic tests of the amniotic fluid in the womb can be done to diagnose Tay-Sachs, so the parents can chose whether to terminate the pregnancy. These tests used to take a long time to show results so they were not so effective in the past. However now they can be done with a simple blood test with results being shown in under 48 hours. The blood samples can be analyzed by enzyme assay or DNA studies. Some Jewish communities have organised pre-marital counselling to help reduce the occurrence of the disease. These methods can reduce the amount of children being born with Tay-Sachs.

In conclusion I cannot decide which theory is the most likely to have caused the high prevalence of Tay-Sachs in Ashkenazi Jews as they are all valid explanations. Even though genetic drift and the founder effect are two different theories, both may have contributed to the high prevalence while the TB epidemic the Jews faced only increased the proportion of carriers in the population. So it is likely that all three theories played a part in keeping the mutation high in Ashkenazi Jews. Regarding the future of the population, it is vital to advertise genetic testing more to the populations at risk as the methods used seem to have been successful in reducing the numbers of children with Tay-Sachs.

Human Genetics: Concepts and Applications (Second edition, 1997) pp. 247-248 by Ricki Lewis


  1. A reasonable overview, although you are rather soft on the TB hypothesis. Why should this apply only to Ashkenazim? See comments on other blog entry on this topic.

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