CCR5-Delta32 allele frequencies in Ashkenazi Jews

This study was carried out to determine the 32-bp deletion allele frequencies in the CCR5 gene (CCR5-Delta32) in various populations of Jews of eastern European origin (Ashkenazi Jews). The total population sample (n = 351) represented Ashkenazi Jews originating from seven geographic groups in Europe. The overall frequency of the CCR5-Delta32 allele was elevated (13.7%), although some important differences in frequencies occurred among the seven countries included in the survey; the frequency was highest (25.9%) in those of Lithuanian origin. There is an apparent trend (r = 0.74) involving a lowering of the Delta32 allele frequencies moving from north to south in the seven populations tested. The Delta32 frequencies obtained were compared to those already published for non-Jewish populations inhabiting the same countries and the differences in frequencies were not significant, with the exception of Lithuania (chi(2) = 2.20, p < 0.03). Founder effect and genetic drift are proposed to explain the elevated values observed in Ashkenazi Jews and those originating from Lithuania.     

Phosphoglycolate phosphatase polymorphism: gene frequencies in three Italian samples

The electrophoretic polymorphism of the PGP locus has been studied in about 1,700 Italians. The sample consisted of individuals from Viareggio (North-Central Italy), Rome (Central Italy) and Cagliari (Sardinia, Southern Italy). Comparison among the three groups showed a high degree of heterogeneity. The Sardinian sample was well differentiated from the other two concerning the frequencies of both the PGP3 and of PGP2 alleles. The frequency of the PGP1 allele varied from 0.900 (Viareggio) to 0.987 (Cagliari). The gene frequencies, together with those available for other European populations were plotted against the latitudes of the different localities sampled and fitted to a North-South cline.     

Genetic polymorphism of delta-aminolevulinate dehydrase in several population groups in Israel

The genetic polymorphism of red cell delta aminolevulinate dehydrase (ALADH) has been investigated in several population groups in Israel: Ashkenazi Jews, non-Ashkenazi Jews from North Africa, Egypt, Turkey, Iraq, Iran, Yemen and the Balkans, and Arabs. The distribution of the ALADH genes was not homogeneous (chi 2 = 36.83; d.f. = 8; p less than 0.0005). A significantly higher frequency of the ALADH2 gene was observed among the Ashkenazi Jews (0.2021) than among the non-Ashkenazi Jews and Arabs (gene frequencies 0.0825-0.1290) or all the other population samples so far studied (Liberia, Japan, Italy, Germany and Spain).     

Phosphoglycolate phosphatase (PGP. E. C. 3..3.18) polymorphism in Magadan inhabitants

PGP phenotype and gene frequency distribution in 457 Russians and 33 Chuckchies is presented. Gene frequencies are: PGP1-0.887 and 0.970; PGP2-0.101 and 0.030; PGP3-0.030 and 0.000, correspondingly. It is shown that frequency of heterozygotes decreases in healthy Russians with increase of duration of dwelling under the North conditions. Such a dynamics causes approaching of PGP phenotype distribution of "long-livers" of the North to that of aboriginal population and moving away from European distribution type.     

Investigations on the ethnic variability of the ABO blood group polymorphism in Iran

112 Iranian population samples with a total of 600954 individuals are analyzed concerning the ethnic variability of ABO allele frequencies. The genetic heterogeneity within and between these population samples is considerable. This heterogeneity is discussed with regard to the ethnohistory of Iran. The most striking ABO allele frequencies are observed in Assyrians, Armenians and Zoroastrians, which differ extremely from that of all the other hitherto studied ethnic groups of Iran. Obviously varying ABO allele frequencies are seen also in Yazdis as well as in Turkomans and Arabs living in Iran. And finally the Iranian Jews reveal clear frequency differences in comparison with all the other Iranian population groups. It can be assumed that the specific ABO allele frequencies found in the above mentioned ethnic groups are connected with their different geographical origin as well as with their marked endogamy.     

Ethnic differences in the frequency of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in healthy Israeli populations

Hyperhomocysteinemia is an independent risk factor for arteriosclerotic vascular disease. It can result from deficiencies of co-factors required for homocysteine metabolism and/or from genetic disorders of its metabolism. The association between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and vascular disease is controversial, and may be affected by ethnic origin. A unique feature of the Israeli population is its ethnic diversity. The aim of this study was to study the frequency of the C677T MTHFR mutation in healthy Israeli ethnic groups. The frequency of the mutation was determined in 897 young healthy Jewish and Muslim Arab Israelis of eight different ethnic groups. Marked ethnic differences in the frequency of mutant homozygotes were found, ranging from 2% in Yemenite Jews, 4% in Sephardic Jews, 9% in Oriental Jews, 10% in Muslim Arabs, 16% in North African Jews, and 19% in Ashkenazi Jews. The frequency of mutant homozygotes was significantly higher in Ashkenazi Jews compared to Yemenites Oriental Jews, Sephardic Jews, and Muslim Arabs (chi2 = 12.35p < 0.001, chi2 = 8.17p = 0.004, chi2 = 6.04p = 0.01, chi2 = 6.54 p = 0.01, respectively). Our findings demonstrate the need for matching ethnic background in patients and controls when studying the association between the C677T MTHFR mutation and any disease.     

Protease inhibitor subtypes in some population groups from Israel

Results of protease inhibitor (PI) subtyping on polyacrylamide gel isoelectrofocusing of 599 Israeli non-Jews and 1,393 Israeli Jews are recorded. A discriminant analysis (DS) was performed on frequency data of the 5 PI alleles (M1, M2, M3, S and Z) with data of Europeans, Israeli non-Jews and Israeli Jews. A higher percentage of correct classification was obtained when Jews were treated as a separate population group rather than when distributed in their areas of origin. This suggests a greater resemblance, in the PI system, of the studied Jewish groups to each other than of the European Jews to Europeans and of the studied mediterranean Jews to Middle Eastern non-Jews. A cluster analysis disclosed distance relationships in a similar direction. PI allele distribution, in the studied Jewish samples, has the following characteristics: Jews share with Middle Eastern non-Jews an absence of PIZ, which is present in Europeans. Mediterranean Jews have higher frequencies than Ashkenazi Jews, of PIS alleles, which are absent in Middle Eastern non-Jews. European Jews are closer to the Europeans than Middle Eastern Jews in their PIM allele frequencies. An original common gene pool of Jews with Middle Eastern non-Jews is postulated, of which the Sephardic (Spanish) and Middle Eastern Jews differ, now, in having PIS, and European Jews differ in having slightly lower PIM3 and PIM2 and higher PIM1 frequencies. A possibility of admixture and selection, affecting different alleles in different Jewish communities at different times, is suggested to have contributed to the present-day deviations from the supposed original gene pool.     

Transferrin subtypes in Iran

The frequency of transferrin Tf C subtypes has been determined by double one-dimensional electrophoresis of plasma samples from Moslems (n = 91), Zoroastrians (n = 97), Jews (n = 88) and Armenians (n = 88) of Iran. The Zoroastrians show the lowest frequency of TfC1 (0.4999) and highest frequencies of TfC2 and TfC3 (.02215, and 0.2783, respectively). The Jews have the highest TfC1- and the lowest TfC2- and TfC3 frequencies (0.8011, 0.1478, and 0.0512, respectively). It could be shown that the differences between Zoroastrians and Jews are highly significant (p less than 0.001). Arbitrary subtyping of transferrin Tf B and TfD phenotypes could be done on samples from three regional groups of Iran: North: n = 282, Central: n = 548, and South: n = 587 into Tf B (Iran 1, 2, 3 and 4) and Tf D (Iran 1, 2 and 3) was performed according to mobilities relative to the transferrin C protein during polyacrylamide gel electrophoresis and by relative pI deviations from the Fe2-transferrin C1 protein after isoelectric focussing. The allele frequencies found in the total sample (n = 1417) are: TfB1 = 0.0003, TfB2 = 0.0010, TfB3 = 0.0042, TfB4 = 0.0007; TfD1 = 0.0017, TfD2 = 0.0014, and TfD3 = 0.0010.     

Genetic heterogeneity of delta-aminolevulinate dehydrase and phosphoglycolate phosphatase in north-west Spain

The distribution of delta-aminolevulinate dehydrase and phosphoglycolate phosphatase phenotypes was analyzed in 500 autochthonous individuals from the Galician population (north-west Spain). The gene frequencies for PGP2 and ALADH2 obtained in Galicia have proved to be the lowest of all the European populations so far examined. Comparisons with other world populations were also made.     

R620W functional polymorphism of protein tyrosine phosphatase non-receptor type 22 is not associated with pulmonary tuberculosis in Zahedan, southeast Iran

The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, which encodes an intracellular lymphoid-specific phosphatase, is considered an important regulator of T-cell activation. We investigated a possible association between the PTPN22 C1858T (R620W) polymorphism and pulmonary tuberculosis in an Iranian population. Single nucleotide polymorphisms of PTPN22 C1858T (rs2476601) were genotyped in 172 pulmonary tuberculosis cases and 204 normal subjects from Zaheden, Iran. Frequencies of genotypes CC, CT and TT of the PTPN22 C1858T polymorphism were 98.3, 1.7 and 0% in the pulmonary tuberculosis patients, and 96.1, 3.9 and 0% in the control group, respectively (P = 0.239). The frequency of the minor (T) allele was 0.8% in pulmonary tuberculosis patients and 2.0% in controls. Significant differences were not observed in genotype or allele frequencies of PTPN22 C1858T in the comparison between pulmonary tuberculosis patients and healthy subjects in our Iranian population sample.     

Genetic polymorphisms in southwest Alaskan Eskimos.

Allele frequencies of 28 genetic loci were determined in subsets (n ranged from 52 to 698) of a sample of Yupik-speaking Eskimos from southwestern Alaska. Five loci were monomorphic (Kell Kp (b+), ADA1, AK1, HBA, and PGDA). At the other loci, the most frequent alleles were AB00 (0.580), Fya (0.960), Jkb (0.513), Ms (0.333), CDe (0.591), ACPA (0.566), ESD1 (0.890), GLO2 (0.736), GPT1 (0.653), Hp2 (0.654), PGM1 (0.836), PGP1 (0.972), and UMPK1 (0.873). The most frequent immunoglobulin allotype Gm(1;21) occurred with a frequency of 0.829. The HLA alleles that occurred with highest frequencies were A24 (0.626), Bw48 (0.184), Cw3 (0.404), and DR4 (0.329). The average heterozygosity at all loci was 0.423. Based on the presence of the European allotype, Gm3;23;5,11,13, the proportion of European admixture in the Eskimo population was estimated to be 2.1%.     

Characterization of pharmacogenetically relevant CYP2D6 and ABCB1 gene polymorphisms in a Portuguese population sample

Differences in metabolism of drugs can lead to severe toxicity or therapeutic failure. In addition to cytochrome P450 2D6, which plays a critical role in drug metabolism, ABCB1 encoded P‐glycoprotein (PGP) is also an important determinant in drug bioavailability. The genes encoding these molecules are highly variable among populations and, given their clinical importance in drug therapy, determining CYP2D6 and ABCB1 allele frequencies in specific populations is very important for useful application in clinical settings. In this study the frequency of the pharmacologically relevant CYP2D6*3, *4, *5, *6 allelic variants and gene duplication, and ABCB1 C1236T and C3435T gene polymorphisms and their haplotypes was determined in a population sample of 100 Portuguese healthy subjects. CYP2D6 allele frequencies were 1.4% (*3), 13.3% (*4), 2.8% (*5), 1.8% (*6) and 6.1% (gene duplication), with 5% of the individuals classified as PM and 8.4% as UM. The frequencies obtained for the non‐functional alleles and for the CYP2D6 gene duplication are in agreement with other South European populations, and reinforce the previously suggested south/north gradient of CYP2D6 duplications. Allelic frequencies for the ABCB1 polymorphisms were 52% (3435C) and 54% (1236C) and the most common haplotype (1236C‐3435C) occurred with a frequency of 45.5%. Although allele and haplotype frequency data for ABCB1 in Southern Europe is limited, some discrepancies were found with other European populations, with possible therapeutic implications for PGP substrate drugs. Copyright © 2009 John Wiley & Sons, Ltd.     

The common -866G/A polymorphism of the UCP2 gene in healthy Iranians compared with world populations

Uncoupling protein 2 (UCP2) is a member of the mitochondrial transporter superfamily. It is proposed as a candidate gene for obesity. A common G/A polymorphism in the promoter region of this gene is associated with enhanced adipose tissue mRNA expression in vivo. Using a PCR-RFLP method, we genotyped the UCP2 -866G/A polymorphism in 75 unrelated nonobese nondiabetic Iranians. The frequencies of the UCP2 -866G/A genotypes in 75 Iranian normal subjects were 7 (9.4%) for AA, 41 (54.6%) for GA, and 27 (36%) for GG. Significantly higher HDL cholesterol was detected in people with the GG genotype (p = 0.02) compared to individuals with the GA and AA genotypes. The frequency distribution results were compared with data from Japanese, Italians, Germans, Austrians, and Danes. Our allele frequencies were significantly different from the Japanese data from two different reports (P < 0.025) but not from the others. The Japanese data showed a higher frequency of the AA genotype, which is associated with a low prevalence of obesity, than the Caucasian individuals' data did. In conclusion, a single nucleotide polymorphism in the promoter region of the UCP2 gene has a significant association with HDL cholesterol level in Iranian nonobese nondiabetic subjects. Also, our allele-frequency distribution for this single nucleotide polymorphism is closer to European Caucasians than to Japanese in nonobese nondiabetic individuals.     

Ethnic differences in CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) genotypes in Japanese and Israeli populations

CYP2C9 is a major P450 2C enzyme, which hydroxylates about 16% of drugs that are in current clinical use and contributes to the metabolism of a number of clinically important substrate drugs such as warfarin. Ethnic differences in the genetic variation of CYP2C9 have been reported, and might be related to the frequencies of adverse reactions to drugs metabolized by CYP2C9 in different ethnic groups. In the present study, ethnic differences in the CYP2C9*2 and CYP2C9*3 allele distribution in Japanese and Israeli populations were evaluated using a newly developed oligonucleotide based DNA array (OligoArray(R)). The population studied consisted of 147 Japanese and 388 Israeli donors (100 Ashkenazi Jews, 99 Yemenite Jews, 100 Moroccan Jews and 89 Libyan Jews). The CYP2C9*2 [Arg144Cys (416 C>T), exon 3] and CYP2C9*3 [Ile359Leu (1061 A>C), exon 7] genotypes were determined using an OligoArray(R). The accuracy of genotyping by the OligoArray(R) was verified by the fluorescent dye-terminator cycle sequencing method. A Hardy-Weinberg test indicated equilibrium (chi(2)<3.84 is Hardy-Weinberg) in all populations. The CYP2C9*2 genotype (CC/CT+TT) was absent in Japanese (1/0) (OR 0.02), and its frequency was significant in Libyan Jews (0.697/0.303) (OR 2.13; 95% CI 1.07-4.24) compared with Ashkenazi Jews (0.83/0.17), Yemenite Jews (0.899/0.101), and Moroccan Jews (0.81/0.19). The frequencies of CYP2C9*3 genotype (AA/AC+CC) was significantly lower in Japanese (0.986/0.014) (OR 0.08), and was higher in Libyan Jews (0.652/0.348) (OR 3.03; 95% CI 1.5-6.1) and Moroccan Jews (0.77/0.23) (OR 1.69; 95% CI 0.62-3.48) compared with those in Ashkenazi Jews (0.85/0.15) and Yemenite Jews (0.849/0.151). Thus, the CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) variants were rare in the Japanese population, and showed different frequencies in the four Jewish ethnic groups examined.     

Abraham's Children in the Genome Era: Major Jewish Diaspora Populations Comprise Distinct Genetic Clusters with Shared Middle Eastern Ancestry

For more than a century, Jews and non-Jews alike have tried to define the relatedness of contemporary Jewish people. Previous genetic studies of blood group and serum markers suggested that Jewish groups had Middle Eastern origin with greater genetic similarity between paired Jewish populations. However, these and successor studies of monoallelic Y chromosomal and mitochondrial genetic markers did not resolve the issues of within and between-group Jewish genetic identity. Here, genome-wide analysis of seven Jewish groups (Iranian, Iraqi, Syrian, Italian, Turkish, Greek, and Ashkenazi) and comparison with non-Jewish groups demonstrated distinctive Jewish population clusters, each with shared Middle Eastern ancestry, proximity to contemporary Middle Eastern populations, and variable degrees of European and North African admixture. Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry. Rapid decay of IBD in Ashkenazi Jewish genomes was consistent with a severe bottleneck followed by large expansion, such as occurred with the so-called demographic miracle of population expansion from 50,000 people at the beginning of the 15^th century to 5,000,000 people at the beginning of the 19^th century. Thus, this study demonstrates that European/Syrian and Middle Eastern Jews represent a series of geographical isolates or clusters woven together by shared IBD genetic threads.     

Study of the mutation M694V of familial Mediterranean fever in Jews

Familial Mediterranean fever (FMF) is a recessively inherited disorder characterized by episodes of fever with abdominal pain, pleurisy, or arthritis. The familial Mediterranean fever gene, designated MEFV, was recently cloned, and the missense mutation M694V accounting for most of the patients with this disease was identified. The objective of the present study was to establish frequencies of the M694V mutation in three groups of Jews. The subjects studied were 381 Sephardi, 256 Ashkenazi, and 65 Oriental Jews, all male subjects, previously collected for an anthropological study, independent of their FMF status. The M694V mutation in the 702 samples was assessed by amplifying genomic DNA with the use of primers that selectively amplify the normal or altered DNA sequence of the M694V mutation, by the amplification refractory mutation system (ARMS). In our sample of Sephardi Jews, the frequency of the M694V mutation is elevated (10.9%), and this is also the case for Oriental Jews (9.2%). In our sample of Ashkenazis, the M694V allele frequency is very low (0.8%).     

The Group-Specific Component/Vitamin D Binding Protein (GC/DBP) in Jewish Population Groups. Distribution of common and rare alleles. Description of a new variant GC1C51

The distribution of GC phenotypes and alleles was determined in six Jewish population groups from Israel. In Jews of eastern Europe, central Europe and North Africa, the allele distribution was similar to that of European non-Jewish populations. GC^*2 frequencies were considerably lower in Jews of the Middle East and highest in Jews of the Balkan area (Rumania and Bulgaria). A new rare GC variant allele, hitherto not encountered, was observed in six Jewish individuals of various countries of origin. This variant was classified as GC 1C51.     

The polymorphism of red cell esterase D in Italy

1,153 unrelated individuals from three different areas of Italy were tested for the red cell esterase D polymorphism. The gene frequencies found in the three groups do not differ significantly from each other. The EsD2 allele in the total sample has a frequency of 14.6% but it is difficult at the present stage to know if this figure is valid for the whole Italian population. If so, the Italian EsD2 allele frequency lies at the upper limit of the range of the European values. No variant phenotypes were observed.     

Glutathione S-transferase M1 and T1 polymorphisms in Brazilian African descendants

The glutathione S-transferase gene family has an important role in the biotransformation and detoxification of different xenobiotics and endogenous compounds. Two polymorphic genes of this family, GSTM1 and GSTT1, present null alleles that consequently do not produce the respective enzyme when the genotype is homozygous. These polymorphisms are also interesting for population dynamics studies because they have great frequency variations among different ethnic groups and have been reported worldwide. The distribution of these alleles in urban and Amerindian populations in Brazil has been described, but none of those studies reported on African-descended rural populations. The aim of this study was to analyze the genotype frequency distribution of the GSTM1 and GSTT1 null alleles in an urban sample from the Federal District (n = 91) and in four semi-isolated African-descended populations: Mocambo (n = 55), Rio das R?s (n = 117), Riacho de Sacutiaba (n = 34), and Kalunga (n = 68). The GSTM1 and GSTT1 null genotype frequencies in these populations range from 17% to 35% for GSTM1 and from 22% to 44% for GSTT1. These values are similar to those described in other African and African-descended populations. Despite this range, there is no distribution difference among the analyzed populations. Combined GSTM1 and GSTT1 null genotype frequencies range from 6% to 13% and are similar to European-derived populations, suggesting admixture with this ethnic group. This can be interpreted as a European contribution to these African-descended populations. Regarding the urban population in the Federal District, our results suggest an important African and European contribution.     

Apolipoprotein E genotyping among the healthy Kuwaiti population

Apolipoproteins (lipid-free) are lipid-binding proteins that circulate in the plasma of human blood and are responsible for the clearance of lipoproteins. Apolipoprotein E (ApoE) is one of the several classes of this protein family. It acts as a ligand for the low-density lipid (LDL) receptors and is important for the clearance of very low-density lipid (VLDL) and chylomicron remnants. The APOE gene locus is polymorphic, with three major known alleles, APOE*3, *4, and *2. We investigated the distribution of the allele frequency of the APOE gene locus and describe here the genetic variation in four Kuwaiti subpopulations: Arab origin (Arabian peninsula), Arab Bedouin tribes, Iranian origin, and the heterogeneous population. We also describe the use of Spreadex gels in resolving the amplified and digested products of the APOE gene locus. DNA was extracted from whole blood and subjected to PCR and then to RFLP analysis. Allele and genotype frequencies were estimated for the total population and for each subpopulation. Statistical analysis showed no difference in the allele frequencies between the four groups. The frequency of APOE*3 in the Kuwaiti population was highest (88.4%) followed by the frequency of APOE*4 (6.5%) and APOE*2 (5.1%). The genotype and allele frequencies obtained for the Kuwaiti population fell within the reported worldwide distribution for the APOE gene locus. Moreover, the results obtained in this study showed no statistical difference (p > 0.05) between the APOE allele and genotype frequencies between the subgroups for all six genotypes and three alleles, supporting the assumption of admixture in the Kuwaiti population and that the obtained frequencies were in Hardy-Weinberg equilibrium. Finally, we found that the distribution of the APOE alleles in Kuwait differs somewhat from those reported in other Arab populations, suggesting that the Arabs originating from the Arabian peninsula are different from those of Lebanon, Morocco, and Sudan.