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Mutations in the TP53 tumor suppressor gene are the most abundant genetic occurrences in cancer. Some of these mutations lead to loss of function of p53 protein, some are gain of function, and some variants are hypomorphic (partially functional). Currently, there is no clinical distinction between different p53 mutations and cancer therapy or prognosis. Mutations in the oligomerization domain of p53 appear to be quite distinct in function, compared to mutations in the DNA binding domain. Here we show that, like other p53 oligomerization domain mutants, the Ashkenazi-specific G334R mutant accumulates to very high levels in cells and is significantly impaired for the transactivation of canonical p53 target genes. Surprisingly, we find that this mutant retains the ability to bind to consensus p53 target sites. A mouse model reveals that mice containing the G334R variant show increased predisposition to cancer, but only a fraction of these mice develop late-onset cancer. We show that the G334R variant retains the ability to interact with the SP1 transcription factor and contributes to the transactivation of joint SP1-p53 target genes. The combined evidence indicates that G334R is a unique oligomerization domain mutant that retains some tumor suppressor function. [ABSTRACT FROM AUTHOR]

This study aims to shed light on the role of Solomon ben Nathan Ashkenazi, an Ottoman Jewish physician, in Ottoman diplomacy. Despite being a German-born Jew and practicing medicine for several years, Ashkenazi played a crucial part in Ottoman relations with Venice and Poland after arriving in Istanbul. The study explores how Ashkenazi, a physician by profession, attained the position of diplomat and examines the reasons behind his involvement in Ottoman foreign relations. While it is common for Ottoman Jewish physicians to be involved in Ottoman foreign affairs, Ashkenazi's example provides valuable insight into the mechanisms and motivations behind their participation in Ottoman diplomacy. The study shows that Jewish physicians in the Ottoman Empire contributed to Ottoman medicine with their medical expertise and played a significant role in bridging the gap in Ottoman-European relations with their diplomatic skills. [ABSTRACT FROM AUTHOR]

POT1 (Protection of Telomeres 1) is a key component of the six-membered shelterin complex that plays a critical role in telomere protection and length regulation. Germline variants in the POT1 gene have been implicated in predisposition to cancer, primarily to melanoma and chronic lymphocytic leukemia (CLL). We report the identification of POT1 p.(I78T), previously ranked with conflicting interpretations of pathogenicity, as a founder pathogenic variant among Ashkenazi Jews (AJs) and describe its unique clinical landscape. A directed database search was conducted for individuals referred for genetic counselling from 2018 to 2023. Demographic, clinical, genetic, and pathological data were collected and analyzed. Eleven carriers, 25 to 67 years old, from ten apparently unrelated families were identified. Carriers had a total of 30 primary malignancies (range 1–6); nine carriers (82%) had recurrent melanoma between the ages of 25 and 63 years, three carriers (27%) had desmoid tumors, three (27%) had papillary thyroid cancer (PTC), and five women (63% of female carriers) had breast cancer between the ages of 44 and 67 years. Additional tumors included CLL; sarcomas; endocrine tumors; prostate, urinary, and colorectal cancers; and colonic polyps. A review of a local exome database yielded an allelic frequency of the variant of 0.06% among all ethnicities and of 0.25% in AJs. A shared haplotype was found in all carriers tested. POT1 p.(I78T) is a founder disease-causing variant associated with early-onset melanoma and additional various solid malignancies with a high tumor burden. We advocate testing for this variant in high-risk patients of AJ descent. The inclusion of POT1 in germline panels for various types of cancer is warranted. [ABSTRACT FROM AUTHOR]

This research focuses on the social reality of the Jews of Yugoslavia, who are divided into Sephardic and Ashkenazi. They migrated to the Yugoslav territories from different regions and at different times. Their population at the establishment of the Yugoslav state in 1918 was approximately 64,746, which accounted for 0.5% of the total population of Yugoslavia, estimated at around 12 million according to the 1921 census. The majority of the Sephardic Jews were from Andalusia (Spain) and immigrated to Yugoslavia in the 16th century due to the persecution they faced. On the other hand, the Ashkenazi Jews, mostly from Eastern Europe, migrated to Yugoslavia in the 19th century due to mistreatment. Their different historical and cultural experiences resulted in distinctions between the two communities in terms of language, religious practices, and culture. The Yugoslav state recognized them as a religious minority rather than a national one, and the Yugoslav Jews established an official religious institution representing all their sects to the state (the Union of Jewish Religious Communities). They also founded numerous humanitarian, cultural, scientific, and sports associations and had several newspapers. The majority of Yugoslav Jews lived in cities and excelled in professions such as banking, commerce, and industry. Politically, most Yugoslav Jews adhered to the Zionist movement, despite the emergence of opposing movements such as the Integrationist Jews and the Sephardic movement. Yugoslav Jews supported the idea of Jewish nationalism, but not in Palestine, as envisioned by the Zionist movement. The research is divided into an introduction and two sections, with the first section addressing the social reality of Yugoslav Jews, both Sephardic and Ashkenazi, and the second section tracing the political activity of Yugoslav Jews. The research relied on various foreign sources, including English, Serbian, and Croatian documents, as well as several Arabic sources. [ABSTRACT FROM AUTHOR]

PurposeThis study aimed to evaluate uptake and follow-up using internet-assisted population genetic testing (GT) for BRCA1/2 Ashkenazi Jewish founder pathogenic variants (AJPVs).MethodsAcross 4 cities in the United States, from December 2017 to March 2020, individuals aged ≥25 years with ≥1 Ashkenazi Jewish grandparent were offered enrollment. Participants consented and enrolled online with chatbot and video education, underwent BRCA1/2 AJPV GT, and chose to receive results from their primary care provider (PCP) or study staff. Surveys were conducted at baseline, at 12 weeks, and annually for 5 years.ResultsA total of 5193 participants enrolled and 4109 (79.1%) were tested (median age = 54, female = 77.1%). Upon enrollment, 35.1% of participants selected a PCP to disclose results, and 40.5% of PCPs agreed. Of those tested, 138 (3.4%) were AJPV heterozygotes of whom 21 (15.2%) had no significant family history of cancer, whereas 86 (62.3%) had a known familial pathogenic variant. At 12 weeks, 85.5% of participants with AJPVs planned increased cancer screening; only 3.7% with negative results and a significant family history reported further testing.ConclusionAlthough continued follow-up is needed, internet-enabled outreach can expand access to targeted GT using a medical model. Observed challenges for population genetic screening efforts include recruitment barriers, improving PCP engagement, and increasing uptake of additional testing when indicated.

A commentary of the paper 'Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology' that appeared recently in Aging Cell. The possible association of a mitochondrial haplogroup with a disease is frequently discussed. The Humanin peptide encoded by the mtDNA has been shown to play an important regulatory role in cell metabolism. There are variants of Humanin caused by different mutations and it is known that the potent form of Humanin, termed S14G, is found naturally in the people of haplogroup U6a7a1a because they have the mutation m.A2672G; however it has not been shown that having this mutation is indeed beneficial. In their paper, the authors suggest that the mitochondrial DNA mutation, m.C2639T, may be beneficial in people who are in haplogroup N1b and also carry APOE4. The mutation changes the common form of Humanin to Humanin P3S. In the study, the researchers looked at a group of Ashkenazi women who were over the age of 95, and found that a higher proportion of them carried APOE4, suggesting that Humanin P3S protected them against the adverse effects of APOE4. A study in a mouse model supported this finding by showing treatment with Humanin P3S reduced APOE4‐induced brain pathology. In the world population, there are about 500,000 Ashkenazi in haplogroup N1b, predominantly in the subgroup N1b1b1; and there are about 9.5 million non‐Ashkenazi people with the mutation m.C2639T and are therefore also in haplogroup N1b and have Humanin P3S. However, the researchers have yet to show Humanin P3S is of benefit in non‐Ashkenazi people. This paper raises the possibility of a therapeutic use of Humanin P3S in the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

In July 1950, Moroccan Rabbi Yahya Ben Harosh wrote a letter to his students chastising those exposed to ultraOrthodox anti-Zionist influences for disparaging and denigrating Zionist leaders and the founders of the State of Israel. This article discusses the historical background to the letter, including the ideological foundation of the rabbi's vigorous protest: from his position regarding the messianic concept to the religious affirmation of Zionism as a national-liberation movement. As such, Ben Harosh's stimulating letter is not an isolated episode but a reflection of the longstanding religious and ideological antecedents of Zionism, dating back to the 16th century, which contained the main elements of the would-be Zionist endeavour. So much so that it is arguable that the 16th century set in motion a fundamental process worthy of being the departure point of Zionist historiography. [ABSTRACT FROM AUTHOR]

This article reconsiders three years in the lives of Jews in Morocco and their families who chose to immigrate to Israel. Relying on private correspondence between Moroccan Jews in Israel and in Morocco that was secretly intercepted by the Israeli intelligence apparatus, I argue that Moroccan Jews in Israel underwent a major process of radicalization between Moroccan independence in 1956 and the Moroccan uprising in Israel in 1959, known as the Wadi Salib revolt. In the Moroccan-Israeli case, Moroccan Jews introduced race into the Israeli discourse, and sought to leverage this discourse for a redistribution of resources, primarily among Jews. This radicalization initially developed against the backdrop of the Moroccan struggle for independence against French colonialism; however, other anticolonial and antiracist struggles of the 1950s were also influential. Thus, the prevailing assessment of the Wadi Salib revolt solely as "an Israeli event" diminishes the longer trajectories of Moroccan radicalization. [ABSTRACT FROM AUTHOR]

Critical pedagogy makes for an enriched approach to Jewish Studies because of shared principles and values also found in Jewish traditions and teachings. The first step of critical pedagogy is to pose the world as a problem. This article agrees with scholarship suggesting that whiteness and racism are fundamental problems of our time. After synthesizing Jewish Studies with a critical pedagogical approach that focuses on the problems of whiteness and racism, the next important step in critical pedagogy is reflection--in this instance, reflection on the relationship between Judaism, whiteness, and racism. This article uses critical whiteness studies as a theoretical framework for reflecting on these relationships. There are two overarching schools of thought in critical whiteness studies--one being that whiteness can be rearticulated to "antiracist white," and the other arguing that whiteness must be abolished. The following article builds upon the latter, making a proposal for one way that Judaism might contribute to liberation movements led by Black, Indigenous and People of Color toward the abolition of whiteness and racism. Finally, the article explores cultural action, the third step of critical pedagogy, at the ideological and material levels. Bringing critical whiteness studies to Jewish Studies reveals one of the many possible ways that Judaism can help to dismantle whiteness and racism. [ABSTRACT FROM AUTHOR]

Simple Summary: Germline BRCA2 pathogenic variant carriers are associated with prostate cancer risk. Ashkenazi Jewish people are at higher risk of breast cancer due to the high prevalence of specific founder germline BRCA1/2 variants. The distribution of these variants (BRCA1 vs. BRCA2) in Ashkenazi men with prostate cancer is not clear. This systematic review and meta-analysis indicates that germline BRCA1 variants are higher in the Ashkenazi Jewish ethnicity in comparison to non-Ashkenazi men. Instead, BRCA2 variants present a similar distribution between the two considered groups. Background and aims: International guidelines recommend testing BRCA2 in men with prostate cancer, due to the presence of a strong association with this gene. Some ethnicities present disparities in genetic distribution for the relation with specific founder variants. Ashkenazi Jewish people are, importantly, at high risk of breast cancer for their inherited cluster with germline BRCA1/2 variants. However, in Ashkenazi men with prostate cancer, the prevalence of BRCA1 and/or BRCA2 is not well defined. We assessed the frequency of these variants in Ashkenazi vs. non-Ashkenazi men with prostate cancer. Materials and Methods: In accord with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we revised all germline BRCA variants reported in MEDLINE from 1996 to 2021 in Ashkenazi and non-Ashkenazi men with prostate cancer. Results: Thirty-five original studies were selected for the analysis. Among populations from Israel and North America, Ashkenazi Jewish men presented higher prevalence of BRCA1 variants [0.9% (0.4–1.5) vs. 0.5% (0.2–1.1), p = 0.09] and a lower prevalence of BRCA2 variants [1.5% (1.1–2.0) vs. 3.5% (1.7–5.9), p = 0.08] in comparison to the non-Ashkenazi population. Conclusions: Since germline BRCA1 variants are more prevalent and BRCA2 variants are less prevalent in PCa patients of Ashkenazi Jewish ethnicity in comparison to non-Ashkenazi patients, prostate cancer genetic screening in Ashkenazi men should not be restricted to the BRCA2 gene. [ABSTRACT FROM AUTHOR]

The success of the Israeli vampire–crime–comedy series Juda is not at all trivial, to say the least. It dared to adopt a controversial subgenre that is associated with antisemitism and blood libels. Moreover, it deals with social traumas and the ethnic conflict between the Zionist Ashkenazi hegemony and the Mizrahi sector, which accuses the hegemony of oppression and discrimination. Juda expresses a critical agenda: a dissolution of Zionist values as the only solution and chance for redemption, both for the hero and for society. Thus, despite emerging at a time when the horror genre had experienced a late blooming on Israeli screens, its appearance is connected to two other central processes in contemporary Israeli film and television: the incorporation of religion and the ascendancy of the Mizrahi hero. Juda overcomes the inherent problem in the image of the Jewish vampire—first by creating a distinction between a Jewish vampire and a gentile vampire, and second by having a protagonist who is a Mizrahi Jew. [ABSTRACT FROM AUTHOR]

HLA haplotypes were found to be associated with increased risk for viral infections or disease severity in various diseases, including SARS. Several genetic variants are associated with COVID-19 severity. Studies have proposed associations, based on a very small sample and a large number of tested HLA alleles, but no clear association between HLA and COVID-19 incidence or severity has been reported. We conducted a large-scale HLA analysis of Israeli individuals who tested positive for SARS-CoV-2 infection by PCR. Overall, 72,912 individuals with known HLA haplotypes were included in the study, of whom 6413 (8.8%) were found to have SARS-CoV-2 by PCR. A total of 20,937 subjects were of Ashkenazi origin (at least 2/4 grandparents). One hundred eighty-one patients (2.8% of the infected) were hospitalized due to the disease. None of the 66 most common HLA loci (within the five HLA subgroups: A, B, C, DQB1, DRB1) was found to be associated with SARS-CoV-2 infection or hospitalization in the general Israeli population. Similarly, no association was detected in the Ashkenazi Jewish subset. Moreover, no association was found between heterozygosity in any of the HLA loci and either infection or hospitalization. We conclude that HLA haplotypes are not a major risk/protecting factor among the Israeli population for SARS-CoV-2 infection or severity. Our results suggest that if any HLA association exists with the disease it is very weak, and of limited effect on the pandemic. [ABSTRACT FROM AUTHOR]

In 1577, a petty pawnbroker named Ester lost a clasp belonging to a Prague noblewoman, Lady Juliana the Fifth. Having been traded repeatedly between anonymous pawnbrokers, the clasp was eventually tracked down in the Polish city of Poznań, by which time Ester had already fled Prague and taken refuge in Cracow. In this essay, I use the subsequent criminal court case to explore this illuminating episode in the history of the city's Jewish Quarter. Taking place in the late Renaissance, during what has often been referred to as the Jewish "Golden Age," I argue that this dramatic event provides access to the realities of an era often characterized as harmonious. I position pawnbroking as an industry that invited intimate and regular cross-confessional contact, and one that therefore offers up new opportunities to consider the nature of coexistence. By following the movement of both Ester and the pawned clasp from Prague to Poland, I also show how attention to pawnbroking can illuminate a constellation of transregional connections that stretched from Bohemia to the Polish-Lithuanian Commonwealth to its east, revealing the otherwise unrecorded ways in which Prague's Jews were connected to the Ashkenazi diaspora. [ABSTRACT FROM AUTHOR]

This article reexamines the evidence of Jewish presence in Poland from the eleventh to the fourteenth centuries in connection with problems of origins, periodization, and localization of Jewish settlement in Poland. It deals inter alia with questions regarding the balance be¬tween Jewish and Christian evidence, as well as with reports of Jewish presence from neighboring areas of Eastern Europe such as Kievan Rus'. The revaluation of evidence on medieval Polish Jews helps to illuminate the origins of eastern Ashkenazi Jewry, as well as to clarify diverse aspects of the history of early Eastern Europe. Thus, for example, among the most important general conclusions is the lack of continuity across three waves of Jewish migration and settlement in Poland. Since most Polish Jews were descendants of the third wave of Jewish migration into Poland, there is little doubt that the vast majority of them came from Germany and Bohemia, mostly via Silesia. We can also reliably conjecture that the Jewish population of southwestern Rus'--whatever its origins (possibly also at least partially Ashkenazi) and size (possibly reduced by the Mongol conquest)-- came to be integrated with immigrants from the west due to the eastward expansion of Lithuania and Poland during the thirteenth and fourteenth centuries. Thus, most modern Ashkenazi Jewry must go back to the melding of these two communities. [ABSTRACT FROM AUTHOR]

This study is dedicated to those Jews from Romania who established themselves as international filmmakers or important figures of the international cinema industry with remarkable film contributions in Turkey, Germany, France, and the USA, where they won four Oscars and eight nominations. Therefore, we can talk about Romanian Jews as personalities who left a mark on the cinema field and whose work entered world film culture. The article will document how, until WWII, Jews were a large minority in Romania, able to create a distinct culture with by establishing the world's first Yiddish language theatre, while also having an important contribution to Klezmer music. The article also looks at documentaries mirroring the emigration of Romanian Jews to Israel. [ABSTRACT FROM AUTHOR]

We present a unique model of a British genetic carrier screening programme for individuals with Ashkenazi Jewish ancestry that exemplifies a partnership between a publicly funded healthcare service (the NHS) and a charity, Jnetics. This model provides affordable access to carrier screening for severe autosomal recessive diseases increased in this community. Prior to the development of this programme, the British healthcare system only provided Tay Sachs' screening for this community, leaving them at higher risk of having a child with a serious autosomal recessive disease. The Jnetics screening programme is promoted through community and social media campaigns, involves educational outreach, a pre-test genetic counselling service by a dedicated NHS-based genetic counsellor, saliva-based DNA testing, comprehensive reporting and, where required, post-test genetic counselling. The charity raises funds to subsidise the screening. In 6 years, the model has been successfully implemented in hospital and community settings and in schools and universities, aiming to reach those pre-conception. In response to the COVID-19 pandemic, the programme adapted by offering genetic screening virtually and has subsequently expanded in its outreach. Furthermore, the screening panel is currently being expanded to include other conditions increased in the Ashkenazi and also the Sephardi and Mizrahi Jewish communities. An example of innovation and accessibility, providing free screening to all students and disadvantaged individuals, the programme aims to provide a model that can potentially be adopted by other genetically at-risk communities. [ABSTRACT FROM AUTHOR]

BACKGROUND Adolescent hypertension is a major cardiovascular risk factor that may be related to ethnic variability. Contemporary Jews can be divided into three distinct ethnic groups: Ashkenazi, Oriental, and Sephardi origins. The aim of our study was to investigate the association of ethnicity and hypertension among Israeli adolescents. METHODS We conducted a population retrospective cohort study of males and females, aged 16–19, eligible for mandatory military service in the Israeli Defense Forces (IDF) between 1994 and 2013. Medical and sociodemographic data, including body mass index (BMI), age, years of education, residential socioeconomic status, and parents' country of birth, were retrieved. Ethnicity of the parents was based upon their country of birth. The examinees were assigned to a certain ethnicity only if both parents had the same ethnicity. Logistic regression models were applied to compute the odds ratio (OR) and 95% confidence intervals (95% CI) for hypertension among the different Jewish ethnicities. RESULTS The final cohort included 1,445,176 adolescents, of whom 716,289 were born to parents of the same Jewish ethnicity. Ashkenazi ethnicity was associated with an increased risk of hypertension compared to Sephardi and Oriental ethnicities (adjusted OR of 2.93 (95% CI, 2.52–3.41) and 1.56 (1.38–1.77), respectively). Oriental ethnicity was associated with an increased risk of hypertension compared with the Sephardi ethnicity (OR of 1.91 (1.60–2.27)). Similar results were observed in a sub-analysis, which included only Israeli-born examinees. CONCLUSIONS Our results indicate that ethnicity is significantly associated with hypertension among Jewish adolescents. Ashkenazi Jews had the highest risk of hypertension. [ABSTRACT FROM AUTHOR]

Jewish languages contain a component derived from Hebrew and Aramaic, the earliest languages Jews used. We offer a historical comparative analysis of the structure and use of adjectives of Hebrew and Aramaic origin in the diverse spoken and written registers of Judezmo (Ladino, Judeo-Spanish) and Yiddish, the two major Jewish languages of the Sephardim and Ashkenazim of Europe. Attention is paid both to adjectives whose forms are entirely of Hebrew or Aramaic origin, as well as those constructed of bases of Hebrew and Aramaic origin, and derivational morphemes of Hispanic and Turkish origin (Judezmo), and Germanic and Slavic origin (Yiddish). The incorporation of the adjectives within the syntactic and semantic systems of Judezmo and Yiddish is examined, and comparisons made between the relative quantity and function of the adjectives in the two languages. It is meant as a model for the comparative study of the linguistic structures of Jewish languages. [ABSTRACT FROM AUTHOR]

The first New World Jewish settlement was in Recife, then a relatively small city in northeastern Brazil. Portuguese New Christians migrated there in the sixteenth century in search of a freer environment in which to continue practicing the Jewish faith. However, it was not until 1630, when the Dutch conquered the region, that Jews were able to openly observe their religion. With the Portuguese reconquest in 1654, this brief chapter ended. Ashkenazi Jews from Eastern Europe and Germany arrived at the beginning of the twentieth century and flourished for several decades. Assimilation and intermarriage, however, diminished Jewish practices and identity before a revival flourished during the last twenty-five years, which has seen both cultural and religious institutions rebuilt. Still, the long-term viability of this community, far from others in Brazil, is not guaranteed. What follows is an account of the long history of Recife Jewry. [ABSTRACT FROM AUTHOR]

A reevaluation of the anthropological genetics literature on Jewish populations reveals them not simply to be a body of genetically related people descending from a small group of common ancestors, but rather a "mosaic" of peoples of diverse origins. Greek and other pre-medieval historiographic sources suggest the patterning evident in recent genetic studies could be explained by a major contribution from Greco-Roman and Anatolian-Byzantine converts who affiliated themselves with some iteration of Judaism beginning in the first and second centuries ce and continuing into the Middle Ages. These populations, along with Babylonian and Alexandrian Jewish communities, indigenous North Africans, and Slavic-speaking converts to Judaism, support a mosaic geography of Jewish ancestry in Europe and Western Asia, rather than one arising from a limited set of lineages originating solely in Palestine. [ABSTRACT FROM AUTHOR]

In the early seventeenth century, the Jews formally established two separate communities in Amsterdam, the Portuguese Sephardi and the High German Ashkenazi congregations. Until the end of the eighteenth century, medical care for the Amsterdam indigent Jews had been controlled and regulated by the powerful Parnasim, the de facto rulers, of each community. The primary communal organizations that were exclusively responsible for medical care for the poor were the Bikur Holim societies. This approach for the care of the indigent Jewish sick became ineffective in the nineteenth century and was replaced by a hospital-based system. This essay describes how seriously ill indigent Jews in nineteenth-century Amsterdam received hospital care, tracing the establishment and development of the first Ashkenazi and Sephardi hospitals in the city. Although each community established their own hospital, they used different approaches to accomplish this goal.

Background: Historically, three founder mutations in the BRCA1/2 (OMIM 113705; OMIM 600185) genes have been the focus of cancer risks within the Ashkenazi Jewish (AJ) population. However, there are several additional mutations associated with increased susceptibility to cancer in individuals of AJ ancestry. Methods: We report three patients who exemplify the need to keep these additional founder mutations in mind when pursuing hereditary cancer genetic testing of individuals in this population. All gene sequences in this paper were aligned to reference sequences based on human genome build GRCh37/UCSC hg19. Results: review of the literature discusses that the combined risk is 12.36%–20.83% forhaving 1 of the 10 hereditary cancer AJ founder mutations in the BRCA1, BRCA2, CHEK2 (OMIM 604373), APC (OMIM 611731), MSH2 (OMIM 609309), MSH6 (OMIM 600678), and GREM1 (OMIM 603054) genes for individuals of AJ ancestry. Conclusion: We recommend testing for all 10 of these AJ founder cancer susceptibility mutations for individuals within this population as standard screening in order to ensure appropriate cancer risk management and cascade testing. Historically, three founder mutations in the BRCA1/2 genes have been the focus of cancer risks within the Ashkenazi Jewish (AJ) population. However, there are several additional mutations associated with increased susceptibility to cancer in individuals of AJ ancestry. We report three patients who exemplify the need to keep these additional founder mutations in mind when pursuing hereditary cancer genetic testing in this population. A review of the literature discusses that the combined risk of having 1 of the 10 hereditary cancer AJ founder mutations in the BRCA1, BRCA2, CHEK2, APC, MSH2, MSH6, and GREM1 genes for individuals of AJ ancestry is 12.36%–20.83%. We recommend testing for all 10 of these AJ founder cancer susceptibility mutations for individuals within this population as standard screening in order to ensure appropriate cancer risk management and cascade testing. [ABSTRACT FROM AUTHOR]

Purpose: BRCA1 and BRCA2 genotyping results have clinical implications for cancer risk assessment and targeted therapy. Current practice in Israel is to genotype for the predominant BRCA1/2 mutations first, followed by full gene analysis in eligible mutation-negative individuals. This work assessed the rate of non-predominant mutations in BRCA1/2 in ethnically diverse high-risk cases.Methods: Breast and/or ovarian cancer patients who tested negative for the predominant BRCA1/2 mutations were referred for comprehensive BRCA1/2 genotyping if calculated risk for carrying a BRCA mutation was ≥ 10%.Results: Of 1258 eligible patients, 41 (3.3%) carried one of 38 mutations: 3% of Ashkenazi Jews and 3.4% of mixed ethnicities. Detection rate was < 5% among patients diagnosed with cancer younger than 40 or with bilateral breast cancer, and was 5.5% of ovarian cancer patients. Three of the carriers (7.3%) carried gene rearrangements. Three mutations were reported in more than one case.Conclusions: The overall yield of comprehensive BRCA1/2 testing in ethnically diverse high-risk Israeli individuals is 3.3%. This is lower than expected by probability models. A slightly higher rate of BRCA1/2 carriers was seen among ovarian cancer cases. These data should guide BRCA1/2 optimal testing strategy in Israel. [ABSTRACT FROM AUTHOR]

Kufor-Rakeb syndrome (KRS)/PARK9 presents with autosomal recessive young onset Parkinson’s disease (YOPD), spastic paraparesis, abnormal eye movements and facial myokymia. KRS is caused by homozygous/compound heterozygous inactivating mutations in ATP13A2. Two affected siblings (born to non-consanguineous Jewish parents) presenting a similar KRS phenotype (onset age 27, 23), carried compound heterozygous pathogenic variants in ATP13A2: c.217_218insG and c.3057delC. Allele frequency of the c.3057delC mutation was about 100 times higher in Ashkenazi controls in our study (1/190 = 0.00526) and in the Genome Aggregation Database, (GnomAD, 27/10132 = 0.002665) versus non-Ashkenazi controls worldwide in GnomAD (9/264566 = 0.000034018, p < 0.0001). The c.217_218insG mutation is novel and not found in controls or GnomAD. The c.3057delC mutation should be included in the genetic workup of Ashkenazi YOPD patients. [ABSTRACT FROM AUTHOR]

The Jewish community in Israel has become a heterogeneous and even forked structure composed of Middle Eastern and European Jews as a result of immigration from several countries, especially after the 1950s. Today, we hear of existence of different Jewish groups like Ashkenazim, Sephardim, Mizrachim, Falashim, Samirim, and Karaim in Israel. But, it is generally divided binary as West and East under the influence of orientalist perspective. The first of them is Ashkenazim and it is thought that they represent Western culture; the second one is Mizrachim and it is thought that they represent Eastern culture. There have been the social, political, economic and sometimes religious conflict between these two groups since they immigrated to Israel. In this essay, we will first inform about these two groups and then focus on their main matter of conflict and its reason with examples in daily life. [ABSTRACT FROM AUTHOR]

In the early seventeenth century, the Jews formally established two separate communities in Amsterdam, the Portuguese Sephardi and the High German Ashkenazi congregations. Until the end of the eighteenth century, medical care for the Amsterdam indigent Jews had been controlled and regulated by the powerful Parnasim, the de facto rulers, of each community. The primary communal organizations that were exclusively responsible for medical care for the poor were the Bikur Holim societies. This approach for the care of the indigent Jewish sick became ineffective in the nineteenth century and was replaced by a hospital-based system. This essay describes how seriously ill indigent Jews in nineteenth-century Amsterdam received hospital care, tracing the establishment and development of the first Ashkenazi and Sephardi hospitals in the city. Although each community established their own hospital, they used different approaches to accomplish this goal. [ABSTRACT FROM AUTHOR]

The successful completion of the Human Genome Project led to the discovery of the molecular basis of thousands of genetic disorders. The identification of the mutations that cause familial dysautonomia (FD), an autosomal recessive disorder that impacts sensory and autonomic neurons, was aided by the release of the human DNA sequence. The identification and characterization of the genetic cause of FD have changed the natural history of this disease. Genetic testing programs, which were established shortly after the disease-causing mutations were identified, have almost completely eliminated the birth of children with this disorder. Characterization of the principal disease-causing mutation has led to the development of therapeutic modalities that ameliorate its effect, while the development of mouse models that recapitulate the impact of the mutation has allowed for the in-depth characterization of its impact on neuronal development and survival. The intense research focus on this disorder, while clearly benefiting the FD patient population, also serves as a model for the positive impact focused research efforts can have on the future of other genetic diseases. Here, we present the research advances and scientific breakthroughs that have changed and will continue to change the natural history of this centuries-old genetic disease. [ABSTRACT FROM AUTHOR]

The article discusses the concept of hitmazrehut for the decolonialization of sociopolitical theory and practice in Israel and Palestine. It examines the transformation of relations between space, identity and narrative through the social movement activism across national boundaries. It also stresses the ahistorical and orientalist biases of sociological inquiry due to the political system in the region.

Through developing of the concept of hitmazrehut, the article highlights avenues for decolonializing and de-orientalizing sociopolitical theory and practice in Israel/Palestine. Hitmazrehut (literally 'becoming of the East') is understood as the transformation of relations between space, identity, and narrative through an intersectionality framework of social movement activism and intellectual counter-discourse. Exposing the intersections among sites of marginality as well as cultivating localized interpretations of identity (delinked from the orientalist positing of Israel in the 'West') would contribute to the possibility of the formation of transformative coalition building across national boundaries. Hitmazrehut is both an outcome and a necessary process for enabling geopolitical reframing. The article begins with the ahistorical and orientalist biases of sociological inquiry into the region. It continues with an analysis of efforts to localize and re-orient Jewish identity as well as the Mizrahi discursive critique of epistemological violence guiding sociological scholarship, double consciousness and patterns of ethnic passing. [ABSTRACT FROM AUTHOR]

Purpose: Studies evaluating adolescent risk factors for developing acute myeloid leukemia (AML) are virtually nonexistent. We assessed adolescent predictors of AML in adults, with a main focus on adolescent BMI.Methods: The study included 2,310,922 16-19-year-old Jewish Israeli adolescents (mean age 17.3 ± 0.4, 59.5% male), called up for an obligatory health examination. Sociodemographic and health data, including measured weight and height, were gathered. Body mass index (BMI) was examined both as a continuous variable and grouped according to the World Health Organization (WHO) classification and US-CDC percentiles. Bone-marrow-biopsy-verified AML cases diagnosed up to 31 December 2012 were identified by linkage to the Israel national cancer registry. Multivariable-adjusted Cox proportional-hazards models were used to model time to diagnosis.Results: During 47 million person years of follow-up, 568 AML cases were identified (crude incidence rate 1.21/100,000 person years). There was a multivariable-adjusted hazard ratio (HR) of 1.041 (95% CI 1.015-1.068, p = 0.002) per unit BMI. The association was evident in those of Middle Eastern, North African, and European origin. A graded association was evident across the overweight and obese WHO grouping. With the US-CDC grouping, excess risk was evident in overweight but not in obese adolescents, although a test for trend in percentiles was significant (p = 0.004). Borderline associations were noted for origin (p = 0.065) (higher in the predominantly Ashkenazi European origin), sex (higher in women: HR = 1.24 (95% CI 0.99-1.55), and stature (HR = 1.013, 95% CI 1.000-1.026, per cm).Conclusions: Higher BMI in adolescence was associated with increased AML incidence in adulthood in this multiethnic population. [ABSTRACT FROM AUTHOR]

The three novels of Dudu Busi, who was born in Tel-Aviv, on 1969, treat of oriental Jews in Israel during the thirty last years of the twentieth century. Through the study of the protagonists, their behavior, their environment, this study tries to see whether belonging to the oriental community is a reason for exclusion from the higher class of Israeli society and whether members of this community have to deny their roots in order to succeed.

Abstract Objectives To conduct a pilot population-based study within a general practice catchment area to determine whether the incidence of breast cancer was increased in the Ashkenazi population. Design Population-based cohort study. Setting A single general practice catchment area in North London. Participants 1947 women over the age of 16 who responded to a questionnaire about ethnicity and breast cancer. Main outcome measures Incidence of breast cancer, ethnicity. Results This study showed a 1.5-fold (95% CI 0.93–2.39) increase in breast cancer risk in the Ashkenazim compared with the non-Ashkenazi white population. The increased incidence was for both premenopausal and postmenopausal breast cancer (expected incidence pre:post is 1:4 whereas in the Ashkenazim it was 1:1; 51 and 52% of cases respectively). This increase was not shown in the Sephardim. Asians had a reduction in incidence (OR = 0.44; 95% CI 0.10–1.89). Results were adjusted for other risk factors for breast cancer. Conclusion This study showed a 1.5-fold increase in breast cancer rates in Ashkenazim compared with the non-Jewish white population when adjusted for age (i.e. corrections were made to allow comparison of age groups) and this is not observed in the Sephardic population. The proportion of premenopausal breast cancer was just over double that of the general population. This is the first general practice population-based study in the UK to address this issue and has implications for general practitioners who care for patients from the Ashkenazi community.

Background: The Y-chromosome haplogroup Q has three major branches: Q1, Q2, and Q3. Q1 is found in both Asia and the Americas where it accounts for about 90% of indigenous Native American Y-chromosomes; Q2 is found in North and Central Asia; but little is known about the third branch, Q3, also named Q1b-L275. Here, we combined the efforts of population geneticists and genetic genealogists to use the potential of full Y-chromosome sequencing for reconstructing haplogroup Q3 phylogeography and suggest possible linkages to events in population history. Results: We analyzed 47 fully sequenced Y-chromosomes and reconstructed the haplogroup Q3 phylogenetic tree in detail. Haplogroup Q3-L275, derived from the oldest known split within Eurasian/American haplogroup Q, most likely occurred in West or Central Asia in the Upper Paleolithic period. During the Mesolithic and Neolithic epochs, Q3 remained a minor component of the West Asian Y-chromosome pool and gave rise to five branches (Q3a to Q3e), which spread across West, Central and parts of South Asia. Around 3-4 millennia ago (Bronze Age), the Q3a branch underwent a rapid expansion, splitting into seven branches, some of which entered Europe. One of these branches, Q3a1, was acquired by a population ancestral to Ashkenazi Jews and grew within this population during the 1st millennium AD, reaching up to 5% in present day Ashkenazi. Conclusions: This study dataset was generated by a massive Y-chromosome genotyping effort in the genetic genealogy community, and phylogeographic patterns were revealed by a collaboration of population geneticists and genetic genealogists. This positive experience of collaboration between academic and citizen science provides a model for further joint projects. Merging data and skills of academic and citizen science promises to combine, respectively, quality and quantity, generalization and specialization, and achieve a well-balanced and careful interpretation of the paternal-side history of human populations. [ABSTRACT FROM AUTHOR]

Copyright of Clio. Femmes, Genre, Histoire is the property of Belin Editeur and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hileya: Scientific Bulletin / Gileya is the property of GILEYA Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Autosomal recessive polycystic kidney disease (ARPKD) is usually detected late in pregnancies in embryos with large echogenic kidneys accompanied by oligohydramnios. Hundreds of private pathogenic variants have been identified in the large PKHD1 gene in various populations. Yet, because of the large size of the gene, segregation analysis of microsatellite polymorphic markers residing in the PKDH1 locus has commonly been utilized for prenatal diagnosis. Keeping in mind the limitations of this strategy, we utilized it for testing 7 families with affected fetuses or newborns, of which in 5 at least one parent was Ashkenazi, and identified that the same haplotype was shared by the majority of the Ashkenazi parents (7/9). This led us to suspect that they carry the same founder mutation. Whole Exome analysis of DNA from a fetus of one of the families detected an already known pathogenic variant c.3761_3762delCCinsG, an indel variant resulting in frameshift (p.Ala1254GlyfsX49). This variant was detected in 9 parents (5 families), of them 7 individuals were Ashkenazi and one Moroccan Jew who shared the same haplotype, and one Ashkenazi, who carried the same variant on a recombinant haplotype. Screening for this variant in 364 Ashkenazi individuals detected 2 carriers. These findings suggest that although c.3761_3762delCCinsG is considered one of the frequent variants detected in unrelated individuals, and was thought to have occurred independently on various haplotypes, it is in fact a founder mutation in the Ashkenazi population. [ABSTRACT FROM AUTHOR]

This article is based on a study in Arabic by author that formed the final chapter of the bookYahud al-bilad al-‘arabiyyah(The Jews of the Arab Countries) by the late Palestinian historian Khairiyyah Qasimiyyah. It examines the problem of identity among Jews of Arab origin in Israel and the resurgent use of the term ‘Arab Jew’ used by Jewish academics and activists in Israel. It also considers the issues of discrimination and socioeconomic injustice against the Arab Jewish community since the early history of Israel. Finally, it discusses the potential for joint action by Arab Jews and Palestinians for the cause of social justice and pluralism in Israel. [ABSTRACT FROM AUTHOR]