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PubMed1993

Spastic paraparesis associated with human T-lymphotropic virus type I: a clinical, serological, and genomic study in Iranian-born Mashhadi Jews.

The Mashhadi-Jewish community originating in Iran is a closed and ethnically segregated population with a unique history and a high rate of intrafamilial marriage among its members. A high risk of infection by human T-lymphotropic virus type I (HTLV-I) and of adult T-cell leukemia associated with such infection was found in this population. HTLV-I is also associated with a syndrome of progressive spastic paraparesis. We therefore evaluated the occurrence of HTLV-I infection and spastic paraparesis in Mashhadi-born Iranian Jews who immigrated to Israel. We examined 83 Mashhadi-born subjects (52 women, 31 men; mean age, 61 +/- 15.5 years) and 73 age-matched non-Mashhadi Iranian-born Jews. Blood samples were tested for HTLV-I antibodies by particle agglutination test. The polymerase chain reaction (PCR) was used to detect HTLV-I proviral DNA sequences from peripheral blood mononuclear cells. Fifteen Mashhadi-born Jews (18%) were both seropositive and PCR-positive for HTLV-I. Four HTLV-I-seronegative subjects were found to be positive for HTLV-I proviral DNA by PCR. Of the 19 HTLV-I-infected subjects (11 women, 8 men; mean age, 59 +/- 16 years), 13 (68%) had spastic paraparesis of varying severity. There were no signs of myelopathy in the Mashhadi-born subjects who were negative for HTLV-I proviral DNA by PCR. None of the non-Mashhadi Iranian Jews was seropositive or PCR-positive for HTLV-I proviral DNA, or had clinical signs of spastic paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

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↗
PubMed1994

Population diversity and distinct haplotype frequencies associated with ACHE and BCHE genes of Israeli Jews from trans-Caucasian Georgia and from Europe.

Variant alleles of the butyrylcholinesterase gene, BCHE, have often been used to trace the genetic histories of populations. The D70G substitution in BCHE causes prolonged postanesthesia apnea ("atypical" phenotype); H322N substitution in the closely related acetylcholinesterase gene, ACHE, is the basis of the mutually incompatible Yt blood groups. In both genes, additional point mutations were reported to be linked to these phenotypically evident ones. To examine whether the intragenic linkage reported for the ACHE and BCHE mutations in Americans is universal, we studied frequencies of these mutations in trans-Caucasian Georgian Jews, a population that has remained relatively isolated for 1500 years. To this end we employed PCR amplification followed by DNA sequencing and enzymatic restriction and compared the frequencies we found to corresponding reported phenotype data. Georgian Jews' N322 ACHE was a rather low 7.0% and was totally linked to a P446 mutation, in agreement with a recent report. In BCHE, however, G70 was a relatively high 5.8%, and the V497 and T539 mutations were not found, either in Georgian or in Ashkenazi Jews, in contrast to reported findings in Americans. Our findings reveal distinct displays of ACHE and BCHE haplotypes in Georgian Jews and suggest different founder effects, genetic drifts, and/or selection pressures in the evolution of each of these genes.

Acetylcholinesterase↗
PubMed2000

The photoreceptor cell-specific nuclear receptor gene (PNR) accounts for retinitis pigmentosa in the Crypto-Jews from Portugal (Marranos), survivors from the Spanish Inquisition.

The last Crypto-Jews (Marranos) are the survivors of Spanish Jews who were persecuted in the late fifteenth century, escaped to Portugal and were forced to convert to save their lives. Isolated groups still exist in mountainous areas such as Belmonte in the Beira-Baixa province of Portugal. We report here the genetic study of a highly consanguineous endogamic population of Crypto-Jews of Belmonte affected with autosomal recessive retinitis pigmentosa (RP). A genome-wide search for homozygosity allowed us to localize the disease gene to chromosome 15q22-q24 (Zmax=2.95 at theta=0 at the D15S131 locus). Interestingly, the photoreceptor cell-specific nuclear receptor (PNR) gene, the expression of which is restricted to the outer nuclear layer of retinal photoreceptor cells, was found to map to the YAC contig encompassing the disease locus. A search for mutations allowed us to ascribe the RP of Crypto-Jews of Belmonte to a homozygous missense mutation in the PNR gene. Preliminary haplotype studies support the view that this mutation is relatively ancient but probably occurred after the population settled in Belmonte.

Chromosomes, Human, Pair 15↗
PubMed2000

High-resolution Y chromosome haplotypes of Israeli and Palestinian Arabs reveal geographic substructure and substantial overlap with haplotypes of Jews.

High-resolution Y chromosome haplotype analysis was performed in 143 paternally unrelated Israeli and Palestinian Moslem Arabs (I&P Arabs) by screening for 11 binary polymorphisms and six microsatellite loci. Two frequent haplotypes were found among the 83 detected: the modal haplotype of the I&P Arabs (approximately 14%) was spread throughout the region, while its one-step microsatellite neighbor, the modal haplotype of the Galilee sample (approximately 8%), was mainly restricted to the north. Geographic substructuring within the Arabs was observed in the highlands of Samaria and Judea. Y chromosome variation in the I&P Arabs was compared to that of Ashkenazi and Sephardic Jews, and to that of North Welsh individuals. At the haplogroup level, defined by the binary polymorphisms only, the Y chromosome distribution in Arabs and Jews was similar but not identical. At the haplotype level, determined by both binary and microsatellite markers, a more detailed pattern was observed. Single-step microsatellite networks of Arab and Jewish haplotypes revealed a common pool for a large portion of Y chromosomes, suggesting a relatively recent common ancestry. The two modal haplotypes in the I&P Arabs were closely related to the most frequent haplotype of Jews (the Cohen modal haplotype). However, the I&P Arab clade that includes the two Arab modal haplotypes (and makes up 32% of Arab chromosomes) is found at only very low frequency among Jews, reflecting divergence and/or admixture from other populations.

Arabs↗
PubMed2004

Genetic factors and colorectal cancer in Ashkenazi Jews.

The observed increased incidence of colorectal cancer in Ashkenazi Jews compared to other populations is unexplained but likely has a genetic component. The I1307K APC polymorphism/mutation is carried by 6-8% of Ashkenazim and increases the risk of colorectal cancer 1.5-2 fold. There are few differences between the phenotype of colorectal cancer in I1307K carriers and sporadic cases. It is estimated that the mutation accounts for 6% of cases of colorectal cancer in Jews of Eastern European heritage. It should not be the subject of mass screening in Ashkenazi Jews, although it may be important in cases of familial colorectal cancer. Even rarer is the 1906G-->C MSH2 mutation carried by less than 1% of Ashkenazim, but as with other HNPCC mutations likely associated with a high risk of malignancy. Mutations at 15q13-14 are associated with the colorectal adenoma and carcinoma syndrome (CRAC) described in Ashkenazi families. The prevalence of the mutation is not known, nor its significance as a cause of colorectal cancer. Despite the paucity of genetic explanations for the high risk of colorectal cancer in Ashkenazim, that risk warrants aggressive colorectal cancer screening and particular attention to family history of malignancy in all Jews of Ashkenazi descent.

Adult↗
PubMed1987

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↗
PubMed2006

The I1307K APC polymorphism in Ashkenazi Jews with colorectal cancer: clinical and pathologic features.

Colorectal cancer is common in Ashkenazi Jews. The I1307K APC mutation occurs in 6-7% of Ashkenazi Jews and increases the risk of colorectal cancer. This study aimed to describe the clinical, pathologic and epidemiologic features of colorectal cancer in I1307K carriers to determine whether there were any features which might warrant individual screening for the mutation. In all, 215 Ashkenazi Jews with a personal history of colorectal cancer were enrolled. Clinical and family history, pathology reports, and slides were obtained and blood drawn for I1307K determination. The presence of the mutation was determined by PCR from white blood cell DNA. Colorectal cancer pathology slides were read in a blinded fashion. Of the 215 enrolled patients, 26 (12.1%) tested positive for I1307K. There was no difference in the pathologic features between colorectal cancers in Ashkenazi carriers compared to noncarriers. There was no difference in the age at diagnosis or history of second or other primaries. Carriers had an increased likelihood of having a first-degree relative with colorectal cancer (50%) compared to noncarriers (28%, P < 0.04). We could find no distinguishing feature other than family history that characterizes I1307K positive colorectal cancers. We could find no group of Ashkenazi Jews with colorectal cancer for whom screening for I1307K would be clinically useful.

Adult↗
PubMed2003

Daily stresses and uplifts during times of political tension: Jews and Arabs in Israel.

This study examined similarities and differences between Jews and Arabs in Israel in terms of their daily stressful and uplifting experiences and assessed the relation between these experiences and family and life satisfaction. Data were collected from representative samples of 697 Jews and 303 Arabs by using a computerized-assisted telephone interviewing system. Contrary to expectation, Jews reported more sources of hassles than did Arabs, whereas Arabs reported more uplifts. A structural equation modeling multigroup analysis indicated a similar factor suucture for hassles and uplifts in both groups. Family satisfaction was positively related to uplifts but not to hassles. For Arabs, uplifts had a positive effect only on family satisfaction, whereas for Jews they had a positive effect on both family and general life satisfaction.

Adaptation, Psychological↗
PubMed2000

Evidence for recent selection of the CCR5-delta 32 deletion from differences in its frequency between Ashkenazi and Sephardi Jews.

Recent studies have shown higher frequencies of the CCR5-delta 32 allele and the CCR5-delta 32/delta 32 genotype, which confers protection against HIV infection, in northern Europe as compared to Mediterranean countries. Here, we analyse the prevalence of CCR5-delta 32 in 922 HIV seronegative blood donors in Israel to verify its frequency in Jews of Ashkenazi and Sephardi origin. A significant difference (P < 0.001) was found between the CCR5-delta 32 allele frequency in Ashkenazi (13.8%) vs (4.9%) Jews. In contrast, no significant difference was observed in the frequency of the CCR2-641 mutation between Ashkenazi (9.2%) and Sephardi (13.4%) Jews. Using the Island model we calculate that a minimal genetic migration rate of 3% per generation would have been necessary if the higher CCR5-delta 32 prevalence in Ashkenazi is to be fully explained by mixing with the indigenous north-European populations. This putative migration rate is 20-fold higher than that currently estimated from other genes, and would correspond to a non-realistic minimal current admixture of 80%. Thus, our results suggest that a positive selection process for CCR5-delta 32 should have occurred in northern Europe at most a 1000 years ago, after the Ashkenazi Jews separated from their Sephardi kin and moved to north Europe.

Alleles↗
PubMed1991

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↗
PubMedDate not supplied

Consanguinity, intracommunity and intercommunity marriages in a population sample of Israeli Jews.

BACKGROUND: Changes in the marriage patterns of Israeli Jews have been associated with the mass immigration of Jews from many countries over a relatively short period of time. AIM: This study seeks to document consanguineous, intracommunity and intercommunity marriage patterns, and to observe the changes that have occurred over time, and in relation to the level of education and religiousness. SUBJECT AND METHODS: During 1990-1992, 4388 Jewish women were interviewed after delivery in maternity wards throughout Israel. Demographic information was received, with special emphasis on country of origin, community and consanguinity of the couples and their parents. RESULTS: The consanguinity rate among the couples was 2.3%, including 0.8% first cousin marriages, with the highest consanguinity rate among Eastern Jews (7.1%). The rate of intracommunity marriages was 64% (25% Ashkenazim, 22% Sephardim and 17% Eastern Jews). The rate of intercommunity marriages was lowest among Ashkenazim. It rose with the level of education and inversely to the degree of religiousness. CONCLUSION: Over the past decades there has been a decline in consanguineous and intracommunity marriage rates and an increase in intercommunity marriages. Immigrant and ultraorthodox women tended to marry within the community as opposed to Israeli-born women and those with higher educational level who tended to intermarry with other communities as well.

Consanguinity↗
PubMedDate not supplied

Toward resolution of the debate regarding purported crypto-Jews in a Spanish-American population: evidence from the Y chromosome.

BACKGROUND: The ethnic heritage of northernmost New Spain, including present-day northern New Mexico and southernmost Colorado, USA, is intensely debated. Local Spanish-American folkways and anecdotal narratives led to claims that the region was colonized primarily by secret- or crypto-Jews. Despite ethnographic criticisms, the notion of substantial crypto-Jewish ancestry among Spanish-Americans persists. AIM: We tested the null hypothesis that Spanish-Americans of northern New Mexico carry essentially the same profile of paternally inherited DNA variation as the peoples of Iberia, and the relevant alternative hypothesis that the sampled Spanish-Americans possess inherited DNA variation that reflects Jewish ancestry significantly greater than that in present-day Iberia. SUBJECTS AND METHODS: We report frequencies of 19 Y-chromosome unique event polymorphism (UEP) biallelic markers for 139 men from across northern New Mexico and southern Colorado, USA, who self-identify as 'Spanish-American'. We used three different statistical tests of differentiation to compare frequencies of major UEP-defined clades or haplogroups with published data for Iberians, Jews, and other Mediterranean populations. We also report frequencies of derived UEP markers within each major haplogroup, compared with published data for relevant populations. RESULTS: All tests of differentiation showed that, for frequencies of the major UEP-defined clades, Spanish-Americans and Iberians are statistically indistinguishable. All other pairwise comparisons, including between Spanish-Americans and Jews, and Iberians and Jews, revealed highly significant differences in UEP frequencies. CONCLUSION: Our results indicate that paternal genetic inheritance of Spanish-Americans is indistinguishable from that of Iberians and refute the popular and widely publicized scenario of significant crypto-Jewish ancestry of the Spanish-American population.

Chromosomes, Human, Y↗
PubMed1999

Age estimates of two common mutations causing factor XI deficiency: recent genetic drift is not necessary for elevated disease incidence among Ashkenazi Jews.

The type II and type III mutations at the FXI locus, which cause coagulation factor XI deficiency, have high frequencies in Jewish populations. The type III mutation is largely restricted to Ashkenazi Jews, but the type II mutation is observed at high frequency in both Ashkenazi and Iraqi Jews, suggesting the possibility that the mutation appeared before the separation of these communities. Here we report estimates of the ages of the type II and type III mutations, based on the observed distribution of allelic variants at a flanking microsatellite marker (D4S171). The results are consistent with a recent origin for the type III mutation but suggest that the type II mutation appeared >120 generations ago. This finding demonstrates that the high frequency of the type II mutation among Jews is independent of the demographic upheavals among Ashkenazi Jews in the 16th and 17th centuries.

Alleles↗
PubMed2001

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%).

Asian People↗
PubMed2003

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.

Alleles↗
PubMed2004

NOD2/CARD15 genotype and phenotype differences between Ashkenazi and Sephardic Jews with Crohn's disease.

OBJECTIVE: NOD2/CARD15 has been identified as a major susceptibility gene for Crohn's disease (CD). Three mutations, Arg702Trp, Gly908Arg, and Leu1007fsinsC, are associated with CD. The incidence and prevalence rate of inflammatory bowel diseases is two- to four-fold higher in Ashkenazi Jews as compared to non-Jewish Caucasians. The aim of this study was to determine the significance of the NOD2/CARD15 mutations in Jewish CD patients in Israel, and more specifically, to compare the significance of the mutations to the expression of CD in the Ashkenazi and Sephardic Jewish populations. METHODS: Allele frequencies of the mutations were determined in 180 Jewish CD patients, 73 ulcerative colitis patients, and 159 ethnically matched controls. Variants were detected using allele-specific PCR and restriction enzyme digestion assay. Demographic and phenotypic characterizations of the CD patients were determined. RESULTS: The carrier rate of the three mutations in the entire Jewish Israeli CD cohort is 41.1% versus 10.7% in controls (p < 0.0001). The Ashkenazi Jewish CD patients have an increased carrier rate compared to Sephardic Jews (47.4%vs 27.45%, p= 0.034). Association analyses in Ashkenazi Jews reveal odds ratios of 10.5, 9, and 4.8 for carriage of Gly908Arg, Arg702Trp, and Leu1007fsinsC mutations, respectively. Significantly higher rates of smoking, family history of inflammatory bowel diseases, and extraintestinal manifestations were found among the Sephardic CD patients. CONCLUSIONS: NOD2/CARD15 CD-associated mutations confer increased risk mainly to the Ashkenazi Jewish CD patients in Israel. This suggests that NOD2/CARD15 mutations could contribute to the higher incidence and prevalence rates of CD among Ashkenazi Jews.

Adolescent↗
PubMed1998

Engaging in psychotherapy with the Orthodox Jew: a critical review.

A critical overview of the current knowledge of engaging in psychotherapy with a cultural minority, Orthodox Jews, is provided. The various forms of psychotherapy that have been utilized to engage Orthodox Jews in meaningful psychotherapeutic encounters are discussed. Psychodynamic, cognitive, behavioral, couple, family, and group therapies have all been employed with success. The first key in working with cultural minorities, including Orthodox Jews, is patience. Patience is required to allow a therapeutic alliance to develop in which the therapist, the outsider, can be trusted. When patients are reluctant to accept the treatment proposed, patience is necessary to give them the time required to verify the treatment with someone they trust, often their rabbi in the case of the Orthodox Jew. Patience is also valuable when patients request a change in the frame of therapy, such as the use of a chaperon or leaving the door slightly ajar if being treated by a member of the opposite sex. The second key in working with this or any other cultural minority is flexibility. Flexibility is required, to chose treatment modalities that best fit with the patient's beliefs, to respect the patient's beliefs no matter the extent they deviate from the therapist's own, and finally, to be critical of oneself when examining transference and countertransference reactions.

Countertransference↗