Some Middle Eastern Affinities Of The Ashkenazi
[T]here are clear genetic signatures of the Middle Eastern ancestry of the population [of the Ashkenazi] and of shared history with other Jewish groups.
Factor XI deficiency is a bleeding disorder. Usually mild, it can become serious after injury, surgery or childbirth. It is partially dominant: 20–50% of carriers (not just homozygotes) also experience excessive bleeding. It is rare in most populations but quite common among Ashkenazi Jews: the gene frequency is about 5%. Two mutations of approximately equal frequency, E117X and F283L, account for almost all of the Ashkenazi Factor XI cases. The type III mutation, F283L, is found at elevated frequency only among the Ashkenazim, but the type II mutation, E117X, is roughly as frequent among Iraqi Jews and can be found at lower frequency among Sephardic Jews and Palestinian Arabs.
Female heterozygotes for BRCA1 mutations have a very risk high of breast cancer and ovarian cancer. This mutation is apparently lethal in homozygotes, since none has ever been observed, even though the Ashkenazi gene frequency is about 0.6%, surprisingly high for a deleterious dominant. About two-thirds of the Ashkenazi BRCA1 mutations are the 187delAG mutation, while the other third are the 5382insC mutation. The 5382insC mutation seems to be limited to the Ashkenazi, but the 187delAG mutation is found at comparable levels in Iraqi and Moroccan Jews.
Most mutations of APC, the gene causing adenomatous polyposis of the colon, cause huge numbers of polyps of the colon and rectum, leading almost inevitably to colon cancer in early adult life. The disorder is dominant. There is a common APC variant (I1307K) among the Ashkenazi that causes a much milder syndrome in which there are many fewer polyps, usually less than 100. The I1307K mutation increases the risk of colon cancer by a factor of 1.5–2. This variant is very common among the Ashkenazim: the gene frequency is about 4%. It is also found in other Jewish groups at lower levels: the average gene frequency among non-Ashkenazi Jews in Israel is 0.7% (Niell et al., 2003).
There are other alleles at relatively high frequency in Ashkenazim that are even more widely shared with Middle Eastern populations. These are mostly old mutations, probably older than the origin of Jews as an ethnic group, and most are plausibly defences against infectious disease. This category includes alpha-thalassaemia (Rund et al., 2004), familial Mediterranean fever (Aksentijevich et al., 1999) and the 167delT mutation of connexin-26 causing non-syndromic deafness (Meyer et al., 2002).
These mutations show that Ashkenazi Jews and other Jewish groups share common ancestry. The exact extent of shared ancestry is unclear since all these alleles are subject to selection. There is a hint of an odd pattern in which a given mutation first becomes surprisingly common in the ancestral Jewish population, then, much later, becomes even more common among the Ashkenazim, sometimes accompanied by other mutations of the same gene.
Aksentijevich, I., Torosyan, Y., Samuels, J., Centola, M., Pras, E., Chae, J. J. et al. (1999) Mutation and haplotype studies of Familial Mediterranean Fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population American Journal of Human Genetics 64, 949–962.
Meyer, C. G., Amedofu, G. K., Brandner, J. M., Pohland, D., Timmann, C. & Horstmann, R. D. (2002) Selection for deafness? Nature Medicine 8, 1332–1333.
Niell, B., Long, J., Rennert, G. & Gruber, S. (2003) Genetic anthropology of the colorectal cancer susceptibility allele APC I1307K: evidence of genetic drift within the Ashkenazim. American Journal of Human Genetics 73, 1250–1260.
Rund, D., Filon, D., Jackson, N., Asher, N., Oron-Karni, V., Sacha, T., Czekalska, S. & Oppenheim, A. (2004) An unexpectedly high frequency of heterozygosity for alpha-thalassemia in Ashkenazi Jews. Blood Cells Molecules and Diseases 33, 1–3.
Quoted on Sun Jun 17th, 2012