Diversity of beta-globin mutations in Israeli ethnic groups reflects recent historic events (original) (raw)
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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.
Origin and expansion of four different beta globin mutations in a single Arab village
American Journal of Human Biology, 2005
In Israel, as in several countries of the Mediterranean basin, beta-thalassemia is frequent among Arabs, and many different mutations in the b globin gene have been identified. In a single Arab village, three different thalassemia mutations, as well as the sickle-cell mutation, were characterized. Using genealogical data as well as the results of screening in the village population, we were able to demonstrate/speculate on how mutations were introduced into the village and how they later expanded. The sickle-cell mutation became particularly prevalent in the village as the result of a founder effect due to a preference for consanguineous marriages. Am.
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...
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.
Human Biology, 2001
In the present study we report the sequence haplotypes associated with 22 β-globin gene mutations present in Turkey. Nine nucleotide polymorphisms and an (AT) x T y motif located at the 5′ end of the β-globin gene form the sequence haplotypes that were investigated in 204 unrelated βthalassemia and wild-type chromosomes from Turkey. Twelve sequence haplotypes were observed in the chromosomes analyzed and haplotypic heterogeneity was found in the wild-type β-globin genes. Samples from the Black Sea region demonstrated a remarkable level of haplotypic heterogeneity in contrast to the homogeneity present in Central Anatolian samples. Of the 22 β-globin mutations analyzed, 18 were related with single sequence haplotypes. This simple association led to the attempt to determine the origin of these mutations by comparing their frequencies in Turkey with those in other countries and/or the world distribution of the haplotypes carrying them. However, the presence of several exceptions for the "one haplotype/one mutation" rule showed that the β-globin gene cluster is far from static. Each of the IVS-I-110 (G→A), Cd 39 (C→T), IVS-I-6 (T→C), and -30 (T→A) βglobin mutations was associated with a minimum of two sequence haplotypes. This fact is best explained by the likelihood of strong recombination mechanisms taking place, rather than by assuming multiple origins for each of these alleles. According to our results, malarial selection for the oldest βthalassemia allele in Anatolia (i.e., IVS-I-110 G→A) may have occurred between 6500 and 2000 b.c. From that date on, most of the common β-thalassemia mutations in Turkey were established, and by the 13th century a.d. most of them were brought to frequencies close to those observed at present. β-thalassemia is an autosomal recessive disorder characterized by microcytosis and hemolytic anemia resulting from a variety of molecular defects that intervene with the normal synthesis of the β-globin chains of hemoglobin . β-thalassemia constitutes one of the most serious health problems
Investigation of beta globin gene mutations in Syrian refugee patients with thalassemia major
Turkish Journal of Biochemistry, 2019
Objectives This study, detection of beta globin gene mutations in thalassemia major patients who migrated from Syria to Kahramanmaraş region were planned. Materials and methods The study included 35 Syrian national beta thalassemia major patients. Beta globin gene mutations were detected by ARMS (Amplification Refractory Mutation System) method, RFLP (Restriction Fragment Length Polymorphism) method and DNA sequence analysis. Codon 15, codon 9/10, codon 5 and codon 8 mutations, which we could not detect with other methods in our study, were detected by sequence analysis. Results In beta thalassemia major patients, 16 types of mutations were detected, the most common being IVS-I-110 (n=8). Other mutations are according to frequency order IVS-II-745 (n=3), codon 44 (n=3), codon 15 (n=3), IVS-I-110/IVS-I-1 (n=3), codon 5 (n=2), IVS-I-1 (n=2), codon 8/IVS-II-1 (n=2), codon 44/codon 15 (n=2), IVS-II-1 (n=1), codon 39 (n=1), IVS-I-6/codon 5 (n=1), codon 9/10 (n=1), IVS-I-110/codon 39 (n=1...
β S -Globin Gene Cluster Haplotypes in the West Bank of Palestine
Hemoglobin, 2009
Sickle cell disease is an inherited autosomal recessive disorder of the beta-globin chain. In Palestine it is accompanied by a low level of Hb F (mean 5.14%) and a severe clinical presentation. In this study, 59 Palestinian patients, homozygotes for Hb S were studied for their haplotype background. Eight polymorphic sites in the beta-globin gene cluster were examined. The Benin haplotype was predominant with a frequency of 88.1%, followed by a frequency of 5.1% for the Bantu haplotype. One chromosome was found to carry the Cameroon haplotype (0.85%). Three atypical haplotypes were also found (5.95%). Heterogeneity was observed in Hb F production, ranging between 1.5 and 17.0%, whereas the (G)gamma ratio was homogeneous among all haplotypes with a normal amount of about 41%. Our results are in agreement with previous reports of the Benin haplotype origin in the Mediterranean.
On the diversity of beta-globin mutations, a reflection of recent historic events in Israel
American journal of human genetics, 1994
... [PMC free article] [PubMed]; Filon Dvora, Oron Varda, Krichevski Svetlana, Shaag Avraham, Shaag Yechezkel, Warren Tina C, Goldfarb Ada, Shneor Yona, Koren Ariel, Aker Mehmet, AbramovAyala, Rachmilewitz Eliezer A, Rund Deborah, Kazazian Haig H, Oppenheim Ariella. ...
European journal of human genetics : EJHG, 2014
β-Thalassemia is a genetic disease caused by a defect in the production of the β-like globin chain. More than 200 known different variants can lead to the disease and are mainly found in populations that have been exposed to malaria parasites. We recently described a duplication of four nucleotides in the first exon of β-globin gene in several families of patients living in Nord-Pas-de-Calais (France). Using the genotypes at 12 microsatellite markers surrounding the β-globin gene of four unrelated variant carriers plus an additional one recently discovered, we found that they shared a common haplotype indicating a founder effect that was estimated to have taken place 225 years ago (nine generations). In order to determine whether this variant arose in this region of Northern Europe or was introduced by migrants from regions of the world where thalassemia is endemic, we genotyped the first 4 unrelated variant carriers and 32 controls from Nord-Pas-de-Calais for 97 European ancestry i...