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Gc subtypes in some population groups from Israel. Comparison between world population groups and between Jews and non-Jews of the same areas.

Results of Gc subtyping on 1,222 Israelis, Arabs and Jews, are summarized and their gene frequencies are analyzed in comparison with available data on Gc subtypes in non-Jews. A discriminant and a cluster analysis demonstrated that in their Gc subtype frequencies European and non-European Jews resemble the populations of the areas where they lived before immigrating to Israel. A possible explanation for this resemblance, which is seen in some and not seen in other genetic markers in Jews, is suggested here to be connected with the function of Gc as a vitamin D-binding protein.

Ethnicity

Maternal, perinatal and infant health in Bedouin and Jews in southern Israel.

A study has been made of 3,745 Bedouin and 9,422 Jewish babies born in 1972-73 to residents of the Beersheba district of southern Israel (the Negev). Newborn infants weighing less than 1 kg were excluded. Thirty-seven percent of the Bedouin babies were born at home; their mothers tended to be older and of higher parity than those choosing to deliver in hospital. Less than 6% of Bedouin mothers had been to school, compared with 90% of the Jews; 30% were aged under 20 or over 34 years, compared with 18% of the Jews, and 23% were having their seventh or later baby, compared with 12% of the Jews. Mean birth weight of babies born in hospital was about 200 g lower in Bedouin than in Jews, and 11.4% of Bedouin and 6.5% of Jewish infants weighed less than 2.5 kg. There was little variation in complications of labor between the 1,959 Bedouin and 8,877 Jewish women delivered in Beersheba's Soroka Medical Center. The cesarean section rate was 1.8% in Bedouin and 4.3% in Jews, while in 0.3% of Bedouin and 1.4% of Jews labor was induced. Monozygous twinning rates were similar in the two ethnic groups (4.8 and 4.5 sets/1,000 deliveries, respectively) but dizygous twinning was twice as common among the Bedouin as among the Jews (13.0 vs 6.0 sets/ 1,000). Male births accounted for 0.526 and 0.512 of the total in Bedouin and Jews, respectively. Perinatal mortality rates for hospital births were 31.1 and 18.3/1,000 in Bedouin and Jews, respectively. Infant deaths among Bedouin (31.0/1,000) were underreported; the rate was 16.8/1,000 for Jewish infants. Although rates of all specific causes of death were higher in Bedouin than in Jews, patterns of mortality in subgroups based on birth weight, sex, twinning and maternal age were quite similar in the two ethnic groups. There were six reported deaths from tetanus among Bedouin babies. For the cohort of babies born in 1972, admissions to the Soroka Medical Center pediatric wards were recorded in 366 (195.5/1,000) Bedouin and 787 (174.3/1,000) Jewish babies younger than the age of one year. Bedouin admission rates were higher than those of Jews for gastroenteritis (119.1 and 64.5/1,000 respectively), infectious and parasitic diseases (29.4 and 21.9), malnutrition (25.6 and 8.0) and external causes (10.1 and 4.4). Admission rates for bronchitis and pneumonia were, however, lower among Bedouin than Jews in the first six months of life.

Birth Order

Bulgarian Jews in Israel: genetic blood markers. Red-cell antigens, serum proteins and red-cell isozymes.

Two hundred and sixteen unrelated Bulgarian Jews were typed for the following genetic systems: ABO, MNS, Rh, Kell and Duffy of the blood groups; ADA, AK1, ACP1, ESD, GLO, PGD, PGM1 and PGM2 of the red-cell enzymes, and for the serum proteins HP, GC and PI. A comparison of observed gene frequencies with those of two other Sephardi Jewish groups, from Libya and Morocco, disclosed significant heterogeneity in several systems. This was mostly due to Moroccan Jews differing from Bulgarian or from both the Libyan and Bulgarian Jews. A comparison of gene frequencies in Bulgarian Jews with those in Oriental Jews from Iraq and in Ashkenazi Jews from Poland disclosed a similarity between the three groups in Rh, ADA, GLO, PGM1 and HP. The frequencies for the above systems in the three groups were closer to those of Middle Easterners than to those of Europeans. A different pattern was observed for GC and PI, in which Bulgarian resembled Polish Jews and differed significantly from Iraqi Jews. This probably reflects an outcome of convergent adaptive processes.

Adult

High incidence of myeloproliferative disorders in Ashkenazi Jews in northern Israel.

We have analysed epidemiological parameters in 339 patients with myeloproliferative disorders (MPD) diagnosed in northern Israel between 1975 and 1989 as having polycythemia vera (191 patients), agnogenic myeloid metaplasia (AMM) (113) and essential thrombocythemia (ET) (36). Mean average annual incidence was 11.4 per 1 million residents for polycythemia vera, 6.5 for AMM and 2.1 for ET. For all three diseases the average annual incidence increased with age and was 10 times higher in patients over 65 years compared to those less under the age of 45 years. Four percent of all patients had relatives with MPD. Incidence of MPD in Jews was 10 fold higher than expected compared to Arabs and this difference was noted for all 3 diseases. The incidence in Ashkenazi Jews originating from eastern and central Europe, was 10 and 20 folds higher than in Sephardic Jews and Arabs respectively. Mean age at diagnosis of MPD in Arabs and Sephardic Jews was lower than in Ashkenazi Jews (52 and 56 years compared to 64 years P < 0.05). Likewise, mean age at diagnosis was lower in the 11.5% of MPD patients with prior exposure to biological or chemical hazards compared to unexposed individuals (58 years versus 63 years, P < 0.02). These data demonstrate a cluster of MPD in Ashkenazi Jews in northern Israel and emphasize the importance of genetic predisposition possibly interacting with acquired factors in the pathogenesis of these disorders.

Adult

Mutation of the prion protein in Libyan Jews with Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease is a transmissible neurodegenerative disorder that occurs more than 100 times more frequently among Libyan Jews than in the worldwide population. We examined 11 patients with the disease--10 Libyan Jews from Israel and 1 Libyan Jew from Italy--to determine whether abnormalities of the prion protein could be detected in them. Abnormal forms of this host-encoded protein are the predominant if not sole components of the transmissible agent that causes the disease. METHODS: The prion-protein open-reading frame in peripheral-leukocyte DNA from the Italian patient was amplified with the polymerase chain reaction and sequenced. Allele-specific oligonucleotide hybridization was used to assess a prion-protein codon 200 lysine mutation in the 10 Israeli patients and 37 control subjects. RESULTS: The prion-protein sequence in DNA from the Italian patient revealed a single nucleotide change (G----A) at the first position of codon 200 that resulted in a substitution of lysine for glutamate. This substitution was detected in all 10 Israeli patients, 8 of whom had a positive family history of Creutzfeldt-Jakob disease. One patient was homozygous for the lysine mutation, and her clinical course did not differ from that of the patients heterozygous for the mutation. The lysine mutation was not found in one Moroccan Jew from Israel with Creutzfeldt-Jakob disease. CONCLUSIONS: The codon 200 lysine mutation of the prion-protein gene is consistently present among Libyan Jews with Creutzfeldt-Jakob disease, strongly supporting a genetic pathogenesis of their illness. The similarity of the clinical courses of the patient homozygous for this mutation and the patients heterozygous for it argues that familial Creutzfeldt-Jakob disease is a true dominant disorder.

Adult

The blood groups and other heriditary blood factors of Yemenite and Kurdish Jews.

Blood specimens collected fro Yemenite and Kurdish Jews living in Israel were tested for 11 blood group systems 5 plasma protein systems and 9 systems of red-cell enzymes. The results of these tests were combined with those of tests on other Yemenite and Kurdish Jews, reported by Godber et al. (1973), the total data sorted according to the place of origin of the subjects or their parents in the Yemen Arab Republic and Kurdistan respectively. Gene frequencies were calculated for each of the local populations so defined. It is confirmed that the Yemenite Jews show a close relationship to the Yemenite Arabs, but those from the southern part of the Yemen Arab Republic have a higher frequency of African marker genes than those in the north. The Habbanite Jews have a similar rather high frequency of African genes (Bonné et al., 1970). The Kurdish Jews from Iran and northern-western Iraq show a moderate genetic resemblance to the indigenous Kurds of Iran, while those from south-eastern Iraq differ considerably, especially in their low frequency of A1, high B, high CDe (R1) and low cde (r).

Blood Group Antigens

Population genetic studies on Jews. I. The alpha 2HS serum glycoprotein, a polymorphism strongly correlated with latitude.

A sample of Jews subdivided according to the birth-place of their parents or grand-parents have been examined for a large number of genetic markers in the course of a long-term project on the genetics of Jews. We report here the findings concerning 794 Jews studied for the AHSG polymorphism. All the subsamples were in Hardy-Weinberg equilibrium. A highly significant difference was found between Sephardic + Near East Jews and Ashkenazi (AHSG*2 frequencies: 0.184 +/- 0.015 and 0.258 +/- 0.016, respectively). For comparative purposes the data available on Caucasoids have been considered. It turned out that they were neatly arranged along a latitude-AHSG gene frequency cline (0.0092 of AHSG*2 gene frequency increase per degree of increase of latitude) in the explored 30 degrees-60 degrees range (r = 0.97; P much less than 0.001). Of the two Jewish frequencies that could be taken into consideration because of their sufficient sizes, that of the Near East + Sephardic Jews was perfectly in line with the above mentioned cline, while that of the Ashkenazi was somewhat displaced in the sense of being more similar than expected to the other, more southern, Jewish group. Since the only AHSG*2 frequency significantly displaced from the regression line is that of the Ashkenazi, whose ancestors lived until centuries ago in more southern areas, this finding is a strong confirmation of the observed cline.

Africa

The Jew in literature: the hated self.

This paper discusses the special psychological and sociological qualities of the Jew in the literature of novels, plays and short stories. From Shakespeare to Hemingway, the Jew has been assigned a special place in the psyche of the authors here described, reflecting the ongoing cultural bias as it became internalized in the selves of the authors quoted. The Jew of Shakespeare's "Shylock" reflects the 16th century bias of Shakespeare and is at a distance--although with interesting similarities--to the Jew of Hemingway. Two psychological facets of anti-Semitism in literature are primarily discussed: the group-self perception of the Jew as stereotype persona, identified over time with specific peculiarities, and the psychological perceptions (in the quoted literature) to the internalized group-percept.

Humans

A variant of HLA-DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews.

HLA-DR4 is associated with risk for developing rheumatoid arthritis (RA) in most populations. In Israeli Jews, in whom the Dw10 subtype of DR4 predominates, no association of RA with DR4 has been found. The inability to detect an association could be due to the high frequency of DR4-Dw10. We used DNA typing with amplification by the polymerase chain reaction and dot-blotting with allele-specific oligonucleotides to determine DR4 variants in 131 Jewish RA patients living in Israel and 134 controls. In both Ashkenazi Jews and non-Ashkenazi Jews, the rare variant Dw15 (previously identified in Japanese populations and in Japanese patients with RA) was found to be the main allele associated with the risk of developing RA (relative risk = 9.2, corrected P less than 0.001). However, this low-frequency allele could be responsible for susceptibility in only 11.5% of the patients. Susceptibility for rheumatoid factor-positive RA was associated with Dw4 and Dw15; the risk for rheumatoid factor-negative RA was associated only with Dw14. The distribution of the HLA-DQ alleles associated with DR4 showed that more than half of the RA patients with Dw15 also had HLA-DQw2. The frequencies of DQw7 and DQw8 were not different in RA patients compared with controls. The results suggest that, as in other populations, susceptibility for the development of RA in Israeli Jews is associated with DRB1 locus alleles of the DR4 group.

Alleles

HLA-Dw clusters associated with DR4 in Israeli Jews and the definition of a new DR4 associated Dw subtype: Dw"SHA".

A homozygous typing cell (HTC), that identifies a newly defined HLA-Dw determinant Dw"SHA," is described. The donor of the HTC was a Yeminite Jew and an offspring of first cousin marriage. This cell is not included in the known DR4-associated specificity clusters Dw4,Dw10,Dw13,Dw14,Dw15, or the provisional cluster Dw"KT2." Dw"SHA" was shown to segregate with DR4 positive haplotypes in family analysis, and in a population study was present in three of 43 unrelated DR4 positive individuals. This new Dw determinant was detected in Israeli Jews of Yemenite origin bearing the haplotype HLA-Bw41,DR4,DQw3. This indicates that Bw41,DR4,DQw3,Dw"SHA" may represent a typical allele combination in Yemenite Jews. Among 43 DR4 haplotypes in Israeli Jews, Dw10 had the highest antigen frequency (41.8%), whereas in American Caucasoids and in Japanese, Dw4 and Dw15 were most frequent, 44% and 40.5%, respectively.

Asian People

Evolution of a genetic disease in an ethnic isolate: beta-thalassemia in the Jews of Kurdistan.

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. We traced the origin of the mutations to specific geographic regions within Kurdistan. This information, supported by haplotype analysis, suggests that thalassemia in central Kurdistan (northern Iraq) has evolved primarily from multiple mutational events. In Turkish Kurdistan, the primary mechanism is genetic admixture with the local population. In Iranian Kurdistan, a founder effect appears to be partly responsible. We conclude that several evolutionary mechanisms contributed to the evolution of beta-thalassemia in this small ethnic isolate.

Base Sequence

The gene for familial Mediterranean fever in both Armenians and non-Ashkenazi Jews is linked to the alpha-globin complex on 16p: evidence for locus homogeneity.

Familial Mediterranean fever (FMF) is a recurrent inflammatory disorder characterized by short episodes of fever, peritonitis, pleuritis, and arthritis. While FMF has been shown to be inherited in an autosomal recessive fashion in both non-Ashkenazi Jews and Armenian families, clinical differences have raised the possibility of genetic heterogeneity. As its pathogenesis is unknown, mapping of the gene for FMF may provide the first objective method for early and accurate diagnosis of this disease. After excluding 45% of the entire human genome, we studied 14 Armenian and 9 non-Ashkenazi Jewish families with FMF and tested linkage with the alpha-globin locus on chromosome 16. Analysis of the PvuII length polymorphism of the 3' HVR (hypervariable region) probe showed significant linkage with the FMF gene (maximum lod score [lodmax] = 9.76 at maximum recombination fraction [theta] = .076). In the Armenians, the lodmax = 3.61 at theta = .10; and for the non-Ashkenazi Jews, lodmax = 6.28 at theta = .06. There was no evidence for genetic heterogeneity between the Armenians and the non-Ashkenazi Jews (chi 2 = 1.28; P = .26) or within either ethnic group (chi 2 = .00; P = .50). Thus, the gene for FMF is linked to the alpha-globin complex on chromosome 16p in both non-Ashkenazi Jews and Armenians.

Armenia

Familial leukopenia among Yemenite Jews.

Benign familial leukopenia was found in 75 of 200 healthy Yemenite Jews examined. The leukopenia was not a constant finding and was not associated with a tendency toward infection. HLA typing showed no significant differences in the frequency of the various HLA antigens between the subjects with and without leukopenia. No similarity was found between the HLA of the Yemenite Jews with leukopenia and that reported in black Africans with benign familial leukopenia. The suggestion of a genetic contribution from African blacks to Yemenite Jews is not supported by these results. The question remains to be answered whether the familial leukopenia in Yemenite Jews and black Africans is the result of a mutation.

Adolescent

High frequency of congenital adrenal hyperplasia (classic 11 beta-hydroxylase deficiency) among Jews from Morocco.

Steroid 11 beta-hydroxylase deficiency is relatively frequent in Israel among North African Jews. Over a 39-year period, 38 affected individuals from 25 families were diagnosed. Nineteen families came from Morocco, and in another 2, one parent came from Morocco (80% of all parents). Demographic studies showed that most of their grandparents were born in the region of the Atlas Mountains. In Israel, the overall incidence of the disorder is estimated between 1 in 30,000 to 1 in 40,000 births, but in offspring of Moroccan Jews the ratio is 1 in 5,000 to 1 in 7,000, with an allele frequency of 1 in 70 to 1 in 84 and a carrier frequency of 1 in 35 to 1 in 42. The clinical expression is characterized by a wide range of variability in the signs of androgen and mineralocorticoid excess. Virilization in the female ranged from enlarged clitoris in the mildest forms, to markedly hypertrophied clitoris with penile urethra and fused labial-scrotal folds in the most severe forms. Hypertension causing vascular accidents and death was observed in both severe and mildly virilized patients, whereas masculinized females were sometimes normotensive. Based on historical evidence, the origin of the ancestors, and the onomastic analysis of the families surnames, we propose that the mutation of 11 beta-hydroxylase deficiency in Jews from Morocco may have originated in either the ancient Jewish settlers or the native Berber tribes who lived in the region of the Atlas Mountains in the southern region of Morocco before the destruction of the Second Temple by the Romans, in the year 70 C.E.

Adrenal Hyperplasia, Congenital

Ethnic communities in Israel: the genetic blood markers of the Moroccan Jews.

One hundred and ninety-six Moroccan Jews now settled in Israel were typed for 7 blood groups, 12 red cell enzymes and 2 plasma protein systems. Their blood group picture is in agreement with results previously obtained on different samples of Moroccan Jews: rather high B in ABO, somewhat elevated frequencies of cDe and cDE in Rh and K in Kell. Differences in various blood markers exist between them and other North African Jewish communities. This fact, together with data on disease distribution and HLA frequencies, supports our assumption that Jews in the North African diaspora lived as small secluded isolates even within the same geographical zones. Comparisons with meager data on the neighboring non-Jewish populations do not disclose any resemblance to either Arab or Berber inhabitants of Morocco.

Blood Group Antigens

Lung cancer histology in major ethnic groups among the Jews. Israel, 1962-1982.

Lung cancer rates in Israel are lower than in other Western countries, not explainable by smoking habits. Due to the different relation of Squamous cell carcinoma (SqCC) and Adenocarcinoma (AC) with smoking it was of interest to study the histologic distribution in Israel. A total of 7508 histologically confirmed lung cancer cases among Jews were studied in the period 1962-82. SqCC was the leading tumor-type in Jewish men and AC in Jewish women. European-American born males in the last study period showed a decrease in SqCC rate while Asian-African born males showed a steep increase in SqCC rate, most prominent among the younger age-groups. Rates of AC increased in both, European-American and Asian-African males, but more steeply in the latter in most age-groups. Only for Large cell carcinoma were the overall rates higher in Asian-African than in European-American born males. SqCC increased in European-American born females and also steeply increased in the over 55 years old Asian-African born females. AC increased in European-American born females (both young and old), but only in the young Asian-African born females (decreasing in the older). European-American born Jews still have higher rates of both, more and less smoking related lung cancer histological types, than Asian-African born Jews. The steep increase in rates of some of the histological types in the latter with the pronounced increased in the younger age-groups is expected to cause a change in the ethnic rate-ratio which has already been demonstrated for the overall lung cancer rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma