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Evolution of a genetic disease in an ethnic isolate: beta-thalassemia in the Jews of Kurdistan
Proceedings of the National Academy of Sciences of the United States of America, 1991
beta-Thalassemia is a hereditary disease caused by any of 90 different point mutations in the beta-globin gene. Specific populations generally carry a small number of mutations, the most common of which are those that are widely distributed regionally. The present study constitutes an extensive molecular characterization of this disease in a small, highly inbred ethnic group with a high incidence of beta-thalassemia--the Jews of Kurdistan. An unusual mutational diversity was observed. In 42 sibships 13 different mutations were identified, of which 3 are newly discovered: a C----A transversion at -88 to the cap site, a frameshift in codon 36/37, and an A----G transition in the polyadenylylation signal. Four of the mutations are unique to Kurdish Jews and have not been discovered in any other population. A fifth was found outside Kurdish Jews only in an Iranian from Khuzistan, a region bordering Kurdistan. Two-thirds of the mutant chromosomes carry the mutations unique to Kurdish Jews...
An unexpectedly high frequency of heterozygosity for α-thalassemia in Ashkenazi Jews
Blood Cells, Molecules, and Diseases, 2004
a-Thalassemia is among the world's most common single gene disorders, which is most prevalent in the malaria belt. This geographic distribution has been attributed to a selective advantage of heterozygotes against this disease. Unexpectedly, we have found a high frequency of heterozygosity for deletional a-thalassemia (Àa 3.7) in Ashkenazi Jews (carrier frequency of 7.9%, allele frequency of 0.04). This population has resided in temperate climates for many centuries and was therefore not subjected to malarial selection pressure. In comparison, heterozygosity for h-thalassemia, which is highly subject to malarial selection pressure, is very low (estimated <0.1%) in this group. It is possible that founder effect and genetic drift have contributed to the high frequency of deletional a-thalassemia in Ashkenazim, as may occur in closed populations. Alternatively, we hypothesize that positive selection pressure for an as yet unknown linked allele on chromosome 16 may be a significant factor leading to this high frequency.
Diversity of beta-globin mutations in Israeli ethnic groups reflects recent historic events
American journal of human genetics, 1994
We characterized nearly 500 beta-thalassemia genes from the Israeli population representing a variety of ethnic subgroups. We found 28 different mutations in the beta-globin gene, including three mutations (beta S, beta C, and beta O-Arab) causing hemoglobinopathies. Marked genetic heterogeneity was observed in both the Arab (20 mutations) and Jewish (17 mutations) populations. On the other hand, two ethnic isolates--Druze and Samaritans--had a single mutation each. Fifteen of the beta-thalassemia alleles are Mediterranean in type, 5 originated in Kurdistan, 2 are of Indian origin, and 2 sporadic alleles came from Europe. Only one mutant allele--nonsense codon 37--appears to be indigenous to Israel. While human habitation in Israel dates back to early prehistory, the present-day spectrum of beta-globin mutations can be largely explained by migration events that occurred in the past millennium.
Diversity of β-globin mutations in Israeli ethnic groups reflects recent historic events
American journal of …, 1994
We characterized nearly 500 P-thalassemia genes from the Israeli population representing a variety of ethnic subgroups. We found 28 different mutations in the P-globin gene, including three mutations (P5, pc, and POAb) causing hemoglobinopathies. Marked genetic heterogeneity was observed in both the Arab (20 mutations) and Jewish (17 mutations) populations. On the other hand, two ethnic isolates-Druze and Samaritans-had a single mutation each. Fifteen of the P-thalassemia alleles are Mediterranean in type, 5 originated in Kurdistan, 2 are of Indian origin, and 2 sporadic alleles came from Europe. Only one mutant allele-nonsense codon 37appears to be indigenous to Israel. While human habitation in Israel dates back to early prehistory, the present-day spectrum of P-globin mutations can be largely explained by migration events that occurred in the past millennium.
Annals of Human Genetics, 2005
Beta thalassemia is an autosomal recessive disorder characterized by reduced (β + ) or absent (β 0 ) beta-globin chain synthesis. In Lebanon it is the most predominant genetic defect. In this study we investigated the religious and geographic distribution of the β-thalassemia mutations identified in Lebanon, and traced their precise origins. A total of 520 β-globin chromosomes from patients of different religious and regional backgrounds was studied. Beta thalassemia mutations were identified using Amplification Refractory Mutation System (ARMS) PCR or direct gene sequencing.
Beta-thalassemia genes in French-Canadians: haplotype and mutation analysis of Portneuf chromosomes
American journal of human genetics, 1990
beta-Thalassemia minor occurs at approximately 1% frequency in French-Canadians--in families residing in Portneuf County (population approximately 40,000) of Quebec province. We found eight different RFLP haplotypes at the beta-globin gene cluster in 37 normal persons and in 12 beta-thalassemia heterozygotes from six families. beta-Thalassemia genes in these families associated with two haplotypes only: Mediterranean I and Mediterranean II. There were two different beta-thalassemia mutations segregating in the Portneuf population: an RNA processing mutation (beta(+)IVS-1,nt110) on haplotype I (five families) and a point mutation leading to chain termination (beta(0) nonsense codon 39) on haplotype II (one family). The distribution of 5' haplotypes on normal beta A Portneuf chromosomes compared with other European populations was most similar to that in British subjects (data for French subjects have not yet been reported). Genealogical reconstructions traced the ancestry of carr...