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PubMed2004

The peculiar pattern of mortality of Jews in Moscow, 1993-95.

Russian Jews, particularly men, have a large mortality advantage compared with the general Russian population. We consider possible explanations for this advantage using data on 445,000 deaths in Moscow, 1993-95. Log-linear analysis of the distribution of deaths by sex, age, ethnic group, and cause of death reveals a relatively high concentration of endogenous causes and a relatively low concentration of exogenous and behaviourally induced causes among Jews. There is also a significant concentration of deaths from breast cancer among Jewish women. Mortality estimates using the 1994 micro-census population as the denominator reveal an 11-year Russian-Jewish gap in the life expectancy of males at age 20, but only a 2-year life-expectancy gap for women. Only 40 per cent of the Russian-Jewish difference for men, but the entire difference for women, can be eliminated by adjustment for educational differences between the two ethnic groups. Similarities with other Jewish populations and possible explanations are discussed.

Age Distribution↗
PubMed1985

In search of the saddiq: visitational dreams among Moroccan Jews in Israel.

Folk veneration of saints (hagiolatry) plays a major role in the lives of many Moroccan Jews living in Israel and constitutes a basic ingredient of their distinctive ethnic identity. In this context, pilgrimages to the saint's tomb and visitational dreams, in which he appears in person or in some symbolic guise, are related phenomena through which the linkage to the saint is maintained and his blessing is granted to his adherents. This paper is concerned with visitational dreams collected among Moroccan Jews in a major pilgrimage center in northern Israel. An attempt is made to show how personal concerns of the dreamers are mediated through the culturally shared idiom of the saint. We discuss the basic structure of visitational dreams, the major life problems conveyed by them (drawing on illustrations from the dream collection), their therapeutic qualities and their significance in the framework of the pilgrimage to the saint's sanctuary.

Adult↗
PubMed1999

The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews.

Three founder mutations in the cancer-associated genes BRCA1 and BRCA2 occur frequently enough among Ashkenazi Jews to warrant consideration of genetic testing outside the setting of high-risk families with multiple cases of breast or ovarian cancer. We estimated the prevalence of these founder mutations in BRCA1 and BRCA2 in the general population of Ashkenazi Jews according to age at testing, personal cancer history, and family cancer history. We compared the results of anonymous genetic testing of blood samples obtained in a survey of >5,000 Jewish participants from the Washington, DC, area with personal and family cancer histories obtained from questionnaires completed by the participants. In all subgroups defined by age and cancer history, fewer mutations were found in this community sample than in clinical series studied to date. For example, 11 (10%) of 109 Jewish women who had been given a diagnosis of breast cancer in their forties carried one of the mutations. The most important predictor of mutation status was a previous diagnosis of breast or ovarian cancer. In men and in women never given a diagnosis of cancer, family history of breast cancer before age 50 years was the strongest predictor. As interest in genetic testing for BRCA1 and BRCA2 in the Jewish community broadens, community-based estimates such as these help guide those seeking and those offering such testing. Even with accurate estimates of the likelihood of carrying a mutation and the likelihood of developing cancer if a mutation is detected, the most vexing clinical problems remain.

Adult↗
PubMed2000

Age estimate of the N370S mutation causing Gaucher disease in Ashkenazi Jews and European populations: A reappraisal of haplotype data.

The N370S mutation at the GBA locus on human chromosome 1q21, which causes Gaucher disease (GD), has a high frequency in the Ashkenazim and is the second-most-widespread GD mutation in the European non-Jewish population. A common ancient origin for the N370S mutation in the Ashkenazi Jewish and Spanish populations has been proposed on the basis of both a similar haplotype for associated markers and an age estimate that suggests that this mutation appeared several thousand years ago. However, a reappraisal of haplotype data, using the Risch formula properly along with a Luria-Delbrück setting of the genetic clock, allows identification of the likely origin of the N370S mutation in Ashkenazi Jews between the 11th and 13th centuries. This result is consistent with the estimated ages of other mutations that are frequent among Ashkenazim, with the exception of type II (Glu117Stop) factor XI deficiency, which is deemed to be >3000 years old, predating the separation of the Ashkenazi and Iraqi Jews. The present finding supports the hypothesis of a more recent origin for the N370S mutation and is consistent with both a founder chromosome transfer from Ashkenazim who assimilated in some European populations and a non-Jewish origin of the European N370S-bearing chromosomes.

Alleles↗
PubMed2001

Hermansky-Pudlak syndrome type 3 in Ashkenazi Jews and other non-Puerto Rican patients with hypopigmentation and platelet storage-pool deficiency.

Hermansky-Pudlak syndrome (HPS), consisting of oculocutaneous albinism and a bleeding diathesis due to the absence of platelet dense granules, displays extensive locus heterogeneity. HPS1 mutations cause HPS-1 disease, and ADTB3A mutations cause HPS-2 disease, which is known to involve abnormal intracellular vesicle formation. A third HPS-causing gene, HPS3, was recently identified on the basis of homozygosity mapping of a genetic isolate of HPS in central Puerto Rico. We now describe the clinical and molecular characteristics of eight patients with HPS-3 who are of non-Puerto Rican heritage. Five are Ashkenazi Jews; three of these are homozygous for a 1303+1G-->A splice-site mutation that causes skipping of exon 5, deleting an RsaI restriction site and decreasing the amounts of mRNA found on northern blotting. The other two are heterozygous for the 1303+1G-->A mutation and for either an 1831+2T-->G or a 2621-2A-->G splicing mutation. Of 235 anonymous Ashkenazi Jewish DNA samples, one was heterozygous for the 1303+1G-->A mutation. One seven-year-old boy of German/Swiss extraction was compound heterozygous for a 2729+1G-->C mutation, causing skipping of exon 14, and resulting in a C1329T missense (R396W), with decreased mRNA production. A 15-year-old Irish/English boy was heterozygous for an 89-bp insertion between exons 16 and 17 resulting from abnormal splicing; his fibroblast HPS3 mRNA is normal in amount but is increased in size. A 12-year-old girl of Puerto Rican and Italian background has the 3,904-bp founder deletion from central Puerto Rico on one allele. All eight patients have mild symptoms of HPS; two Jewish patients had received the diagnosis of ocular, rather than oculocutaneous, albinism. These findings expand the molecular diagnosis of HPS, provide a screening method for a mutation common among Jews, and suggest that other patients with mild hypopigmentation and decreased vision should be examined for HPS.

Adaptor Protein Complex 3↗
PubMed2002

A novel founder mutation in the RNASEL gene, 471delAAAG, is associated with prostate cancer in Ashkenazi Jews.

HPC1/RNASEL was recently identified as a candidate gene for hereditary prostate cancer. We identified a novel founder frameshift mutation in RNASEL, 471delAAAG, in Ashkenazi Jews. The mutation frequency in the Ashkenazi population, estimated on the basis of the frequency in 150 healthy young women, was 4% (95% confidence interval [CI] 1.9%-8.4%). Among Ashkenazi Jews, the mutation frequency was higher in patients with prostate cancer (PRCA) than in elderly male control individuals (6.9% vs. 2.4%; odds ratio = 3.0; 95% CI 0.6-15.3; P=.17). 471delAAAG was not detected in the 134 non-Ashkenazi patients with PRCA and control individuals tested. The median age at PRCA diagnosis did not differ significantly between the Ashkenazi carriers and noncarriers included in our study. However, carriers received diagnoses at a significantly earlier age, compared with patients with PRCA who were registered in the Israeli National Cancer Registry (65 vs. 74.4 years, respectively; P<.001). When we examined two brothers with PRCA, we found a heterozygous 471delAAAG mutation in one and a homozygous mutation in the other. Loss of heterozygosity was demonstrated in the tumor of the heterozygous sib. Taken together, these data suggest that the 471delAAAG null mutation is associated with PRCA in Ashkenazi men. However, additional studies are required to determine whether this mutation confers increased risk for PRCA in this population.

Antigens, Surface↗
PubMed2003

Screening for familial dysautonomia in Israel: evidence for higher carrier rate among Polish Ashkenazi Jews.

Familial dysautonomia (FD) is an autosomal recessive disorder characterized by hereditary sensory and autonomic neuropathies. Although extremely rare in most populations, FD is common among Ashkenazi Jews (AJ), with a calculated carrier frequency of 1 in 30, based on disease prevalence. The gene for FD was recently identified as IKBKAP. One major mutation (IVS2 + 6T --> C) is responsible in >99.5% of cases among AJ. The purpose of this study was to determine the actual frequency of FD carriers in the AJ population in Israel and to determine whether carriers are more frequent among a subpopulation of AJ from Poland. The study group included 1267 Jews of Ashkenazi origin who were referred for routine DNA screening tests. These included 1100 individuals who were full AJ and 167 who were part AJ. None had a family history of FD. Mutation analysis for (IVS2 + 6T --> C) was performed by PCR amplification followed by restriction enzyme analysis. All positive cases were confirmed by DHPLC WAVE( trade mark ). Among the 1100 full AJ tested, 34 were found to be FD carriers (1:32). The incidence of mutation carriers was significantly higher in AJ of Polish descent (1:18) compared to AJ of non-Polish descent (1:99). Among the 167 individuals who were part AJ, there were 3 carriers (1:56). The incidence of FD among AJ, particularly those of Polish background, warrants population screening. Population screening may be performed by denaturing high-performance liquid chromatography.

Base Sequence↗
PubMed1999

Screening Jews and genes: a consideration of the ethics of genetic screening within the Jewish community: challenges and responses.

Screening for genetic disorders, particularly Tay-Sachs Disease, has been traditionally welcome by the Jewish community. I review the history of genetic screening among Jews and the views from the Jewish tradition on the subject, and then discuss ethical challenges of screening and the impact of historical memories upon future acceptance of screening programs. Some rational principles to guide future design of genetic screening programs among Jews are proposed.

Abortion, Therapeutic↗
PubMed1996

Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.

Familial hyperinsulinism (HI) is a disorder of pancreatic beta-cell function characterized by persistent hyperinsulinism despite severe hypoglycemia. To define the molecular genetic basis of HI in Ashkenazi Jews, 25 probands were screened for mutations in the sulfonylurea receptor (SUR1) gene by single-strand conformation polymorphism (SSCP) analysis of genomic DNA and subsequent nucleotide sequence analyses. Two common mutations were identified: (I) a novel in-frame deletion of three nucleotides (nt) in exon 34, resulting in deletion of the codon for F1388 (delta F1388) and (II) a previously described g-->a transition at position-9 of the 3' splice site of intron 32 (designated 3992-9g-->a). Together, these mutations are associated with 88% of the HI chromosomes of the patients studied. 86Rb+ efflux measurements of COSm6 cells co-expressing Kir6.2 and either wild-type or delta F1388 SUR1 revealed that the F1388 mutation abolished ATP-sensitive potassium channel (KATP) activity in intact cells. Extended haplotype analyses indicated that the delta F1388 mutation was associated with a single specific haplotype whereas the 3992-9g-->a mutation was primarily associated with a single haplotype but also occurred in the context of several other different haplotypes. These data suggest that HI in Ashkenazi Jews is predominantly associated with mutations in the SUR1 gene and provide evidence for the existence of at least two founder HI chromosomes in this population.

Animals↗
PubMed1984

A review of theory and research on drinking patterns among Jews.

In an effort to specify the factors relevant to the etiology and prevention of alcoholism, theories have been proposed to account for the low rate of alcoholism among Jews. This paper includes a summary of two major theories that have been developed to explain the drinking patterns among Jews and a review of the data that purportedly support these theories. A critical examination of these studies reveals substantial methodological and interpretive problems that challenge the conclusions that have been generally accepted. Directions for future research are suggested.

Alcohol Drinking↗
PubMed1997

Familial Creutzfeldt-Jakob disease. Codon 200 prion disease in Libyan Jews.

Creutzfeldt-Jakob disease (CJD) is the most prevalent of the human prion diseases, a group of fatal neurodegenerative disorders afflicting both humans and animals. The unique characteristic of these diseases, whether sporadic, dominantly inherited, or acquired by transmission, is the accumulation in the brain of an abnormal isoform (PrPSc) of the cellular prion protein (PrPc). Progress has been made in understanding inherited prion diseases by genetically linking clusters of familial CJD (fCJD) to mutations of the PrP gene (PRNP). One of the largest clusters of fCJD exists among Jews of Libyan origin. The clinical and pathologic manifestations of CJD in this community resemble those seen with sporadic CJD (sCJD), but the incidence is about 100 times higher than in the general population. Initially, this high incidence was attributed to infection via consumption of sheep brains or eyeballs, but a mutation at codon 200 in PRNP resulting in the substitution of lysine (K) for glutamate (E), designated E200K, was identified in this population. The onset of fCJD (E200K) is age dependent and shows nearly complete penetrance by age 85 years. fCJD in Libyan Jews is invariably associated with accumulation of the pathologic isoform PrPSc in the central nervous system. Using mutation-specific antibodies, it was shown that most PrPSc in the brain of these patients originated from the mutant protein. Some studies suggest that mutant PrP may accumulate in brain and other organs due to an impaired degradation, and its accumulation has been postulated to promote conversion into PrPSc. fCJD (E200K) has been transmitted to primates and transgenic mice, highlighting the need to address ethical and public health issues surrounding the possibility of human to human transmission.

Adult↗
PubMed1990

Epidemiology of invasive Haemophilus influenzae type b infections in Bedouins and Jews in southern Israel.

We report the epidemiology of invasive Haemophilus influenzae type b disease requiring hospital intervention in Southern Israel, an area that contains two ethnic populations, Bedouins and Jews. The study is based on 107 blood or cerebrospinal fluid culture-positive cases during the years 1984 to 1988. The annual incidence rate among children younger than 5 years of age was 51/100,000 (48/100,000 for Jews and 58/100,000 for Bedouins). Thirty-nine percent of patients had meningitis, 32% had pneumonia and 31% had otitis media. Epiglottitis was present in only one case (less than 1%). The median age was 8 months. Twenty-six percent of the cases were 6 months old or younger, 75% were 1 year old or younger and 87% were 18 months old or younger. Ninety-five percent of all meningitis cases occurred during the first 18 months of life. A projected number of 2938 hospitalization days and 9.8 deaths/year for a population in which 100,000 births occur yearly was calculated. The major impact of invasive H. influenzae type b infections and the very young age involved justify initiation of H. influenzae vaccine studies in our region.

Age Factors↗
PubMed1978

HLA polymorphism in Israel. I. Jews of Polish extraction.

One hundred and twenty seven randomly selected Polish Jews were studied for their HLA polymorphism. Gene frequencies exceeding 0.1 were detected for A1, A2, Aw19, B14, Bw16 and Bw17. Significant gametic association was observed for (A1, Bw17), (A2, B27), (Aw26, Bw16), (Aw19, B13) and (A28, B14). Although a predominantly Caucasoid population, the Polish Jews show greater resemblance to Middle Eastern rather than to Northern European Caucasoids.

Gene Frequency↗
PubMed1978

HLA polymorphism in Israel. 2. Israeli Jews originating from Russia.

HLA typing of 123 Israel Jews of Russian origin showed a high frequency for HLA--A1, A2, Aw19 and B14, Bw16 and Bw35 of the A and B loci, respectively. The most frequently occuring haplotypes were (A1, B17), (Aw25, B18), (Aw26, Bw16), (Aw19, B13), (Aw23, B5) and (Aw25, Bw35). This study reveals a striking resemblance in the distribution of frequencies of HLA alleles and haplotypes between Russian Jews and two other East European Jewish communities (presented in this issue) of Polish and Rumanian origin.

Gene Frequency↗
PubMed1978

HLA polymorphism in Israel. 4. Israeli Jews originating from Rumania.

The frequencies of 29 HLA antigens of the A amd B loci were studied in 130 Israeli Jews originating from Rumania. The antigens A1, A2, Aw19 and B14, Bw16 and Bw35 occurred with the highest frequencies. The most common haplotypes were (A1, B17), (Aw26, Bw16) and (A28, Bw22). These results are similar to those observed in Polish and Russian Jews.

Gene Frequency↗
PubMed1978

HLA antigens in two Iranian populations: the Armenians and the Jews.

The distribution of HLA phenotype, genotype and haplotype frequencies was studied in two Iranian populations, the Armenians and the Jews. Although the frequencies of most antigens in the Armenians have approximately the average Jewish values, haplotype frequencies are quite different between the two populations. The frequencies of antigens in Iranian Jews are more similar to those in the Mazandaranies, a group of non-Jewish Iranians, than to the Jewish populations from Yemen and Cochin, India.

Armenia↗
PubMed1993

HLA-DR1 and rheumatoid arthritis in Israeli Jews: sequencing reveals that DRB1*0102 is the predominant HLA-DR1 subtype.

Rheumatoid arthritis (RA) is associated with the HLA-DR4 cellular subtypes Dw4 and Dw14 in Caucasians, with Dw15 in Japanese, and possibly with HLA-DR1 in Israeli Jews. Sequencing studies in Caucasians have shown that these molecules share a common amino acid sequence in the third hypervariable region of the DR molecule (AA 67-74: LLEQRRAA or LLEQKRAA), suggesting that this sequence is primarily associated with RA. An important argument in favor of this shared-epitope hypothesis has been the reported association between DR1 and RA in Israeli Jews. However, a later report did not confirm this association, and cellular typing showed that Israeli DR1 consists of three or more subtypes, suggesting that new subtypes might be present. Since no sequencing data on Israeli HLA-DR1 genes have been reported, we sequenced the first domain (AA 10-91) of the DRB1 gene in 12 DR1-positive Israeli RA patients, 5 healthy controls and a homozygous typing cell (HTC), defining the major Jewish cellular HLA-DR1 subtype. DRB1*0102 (DR1 Dw20) was found in 8 RA patients, 3 controls and the HTC "LVA". DRB1*0101 (DR1 Dw1) was found in 4 RA patients and 2 controls. No other DR1 subtypes were encountered. In all 20 DR1 haplotypes, the DRB1*0101 or 0102 allele was associated with DQA1*0101 and DQB1*0501, being identical to the Caucasian DR1 haplotypes. Thus, at the sequence level, we found no basis for the reported extensive cellular heterogeneity of DR1 in the Israeli population.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1979

HLA antigens in genetic neutropenia of Yemenite Jews.

The HLA antigenic system was studied in Yemenite Jews with genetic neutropenia. No deviation in antigen frequency was observed when compared with matched controls from the same ethnic group. HLA antigen frequency and common haplotypes of the Yemenite Jews were found entirely different from those of the African blacks, known to have the same anomaly.

Adult↗