Why do Ashkenazi Jews have an unusually high risk of several genetic diseases?



   
    January 2012          
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Jews, Genes, and Converts to Judaism

By Allen S. Maller

Ashkenazi Jews have an unusually high risk of several genetic diseases, and up until now, no one understood why. Was it just random chance; did some evolutionary advantage play a role in keeping the mutations around; or was it influenced by how many non-Jews converted to Judaism, and entered the Jewish gene pool in each generation?

The answer to this question, said researchers at Stanford University Medical Center, appears to be chance, according to an article in the April 2004 issue of the American Journal of Human Genetics. I think they overlooked an important factor.

Some disease mutations unusually common in Ashkenazi Jews, who make up 90 % of the American Jewish population, include Tay-Sachs disease, some forms of breast cancer, high cholesterol and hemophilia. Four of these disorders, including Tay-Sachs disease, are in a class of diseases called lysosomal storage diseases. People with these disorders lack enzymes that break down toxins into harmless compounds. Instead, the toxins are stored in cellular compartments called lysosomes, where they can build up to high levels and eventually damage the cell.

"It's been known for a long time that Ashkenazi Jews have a high risk of these lysosomal storage diseases," said Neil Risch, PhD, professor of genetics, statistics, and health research and policy at the School of Medicine and one of the senior authors on the study. "The majority opinion has been that there must be some selective advantage for those mutations."

Researchers suspected that lysosomal storage diseases may be similar to sickle cell anemia, in which people who carry two mutated copies of the gene have a disease, but those who inherit one copy of the mutation are protected against malaria. Those people - called carriers - are more likely to be healthy, have more children and pass their mutation on to future generations. If carriers of lysosomal storage mutations were protected against other diseases, those mutations should be more common in Ashkenazi Jewish populations than mutations that cause diseases unrelated to lysosomal storage. Risch and his colleagues analyzed DNA sequences from Ashkenazi Jewish people and compared how common mutations were in lysosomal storage disease genes vs. other disease genes.

The researchers found that mutations in lysosomal storage disease genes are no more common than mutations that cause other inherited diseases in the Ashkenazi Jewish population. This suggests that carriers for lysosomal storage mutations had no benefit over their peers. Instead, Risch said, these mutations were probably present in the Jews who coalesced into the Ashkenazi Jewish population 900 years ago. It just happened that those who founded the Ashkenazi Jewish population had disease mutations and passed them along to their children. It is true that Ashkenazi Jews tend to marry within their own population, but it is also true that European Jews were prohibited by the Church from accepting converts to Judaism. Both factors contributed to keeping those mutations common. When Jews were able to openly seek and welcome converts to Judaism, only a few genetic diseases continued for many centuries.

Risch also looked at the regional distribution of mutations in Ashkenazi Jews, and the age of those mutations. He found three points in time when mutations entered the population. One mutation has been in the Jewish population for 120 generations - around the time the Jewish people formed a distinct population in the Middle East, sometime prior to the time of King David. This mutation causes a type of hemophilia called Factor 11 deficiency type II, and is also found in Sefardic Jews who lived in Muslim countries. Since conversion to Judaism was common from Biblical days to the Roman period (think Ruth and the father of Rabbi Akiba) only this mutation remained for so long in the Jewish population.

The majority of the mutations - including all of the mutations in lysosomal storage genes - entered the population when the Ashkenazi Jews formed a coherent group about 50 generations ago in central and eastern Europe. The final mutations cropped up in the Lithuanian Ashkenazi Jews about 12 generations ago. All of these mutations would have been reduced by the entry of non-Jews into the Jewish gene pool through conversion to Judaism. Because conversion was severely restricted by the European Church during the 4-6th century, converts to Judaism were not able to help eliminate these harmful genetic mutations.

With the rise of conversion to Judaism in the 20th century, these harmful mutations will substantially decline by the end of this century. So it was not just chance that kept these harmful mutations from being eliminated from the Askenazi Jewish population. Those who prevented non-Jews from becoming Jewish also played a part.


Rabbi Maller's web site is: Rabbimaller.com

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from the January 2012 Edition of the Jewish Magazine

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