DOCSLIB.ORG

The Genetic Basis of the Multiple Colorectal Adenoma Phenotype

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Genetic Basis of the Multiple Colorectal Adenoma Phenotype THE GENETIC BASIS OF THE MULTIPLE COLORECTAL ADENOMA PHENOTYPE Oliver Sieber Thesis submitted for the degree of Doctor of Philosophy in the University of London Cancer Research UK January 2004 ProQuest Number: U642895 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U642895 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract Multiple adenoma patients are characterised by 3-100 colorectal adenomas, resulting in an increased risk of colorectal cancer. The disease can be inherited as a Mendelian trait, either autosomal dominant or recessive, or occur sporadically. Approximately 10% of multiple adenoma patients carry a truncating mutation in the APC gene, usually in exons 1-4, exon 9 or the 3’-half of exon 15, producing a diagnosis of AAPC. Two APC missense variants, I1307K and E1317Q, have also been associated with the disease, and some whole-gene deletions have been reported. However, these latter associations have been inconsistent. In contrast, germline mutations in the central region of APC cause classical FAP, a dominant predisposition to hundreds or thousands of colorectal adenomas, resulting in a near 100% risk of cancer. The molecular mechanisms underlying these genotype-phenotype correlations are poorly understood. The genetic basis of multiple adenomas in patients without APC mutation remains to be identified. In this thesis, I have excluded a major role of whole-gene APC deletions in causing AAPC/multiple adenomas. Instead, individuals with such mutations were found to develop classical FAP. I have refined the relationship between germline and somatic mutations at the APC locus in AAPC and classical FAP to show that somatic mutations are constrained by selection for an optimal level of Wnt signalling and that this at least partly determines disease severity. In support of this view, I have provided evidence against a role of truncating APC mutations in causing chromosomal instability. I have shown that the genetic basis underlying multiple adenomas is heterogeneous, by establishing the importance of recessive germline mutations in the base excision repair gene MYH. Some individuals with such mutations were also found to develop classical polyposis. I provide evidence that multiple adenomas are not generally attributable to germline mutations in the Wnt and TGFp/BMP signalling pathways. Acknowledgements I owe thanks to my supervisor Ian Tomlinson for his great support and guidance of my project. He has been of invaluable help in numerous discussions and a continuous source of encouragement. My thanks also go to my collaborators Hanan Lamlum, Karl Heinimann, Lara Lipton, Kelly Woodford-Richens and Michael Crabtree for their intellectual and practical contributions, as well as to my colleagues from the Cancer Research UK Family Cancer Clinic, Colorectal Unit and Polyposis Registry at St Mark's Hospital. I am indebted to the patients for their participation in this study as well as to their respective doctors and pathologists for contributing samples and clinical information. I would also like to thank the staff from the Cancer Research UK Equipment Park, Histopathology and FACS Laboratories for their advice and technical support. I am particularly grateful to the Boehringer Ingelheim Fonds for their financial support. A big thank you goes to all my colleagues in the Molecular and Population Genetics Laboratory who have kept my spirits up during my studies. In particular, I am grateful to Andrew Rowan and Pat Gorman who were readily available for advice and practical help and who also contributed to my work. Lastly, I would especially like to thank my family without whose support and encouragement completion of this thesis would have not been possible. Abbreviations aa amino acid AAPC attenuated adenomatous polyposis coli Alb albumin APC adenomatous polyposis coli BMP bone morphogenic protein BMPRIA bone morphogenic protein receptor type 1A cDNA complementary DNA CGH comparative genomic hybridisation CIN chromosomal instability Co-SMAD common-mediator SMAD C0X2 cyclooxygenase-2 CPKl-a casein kinase 1-a CRC colorectal cancer c^uK CCLWClr ReStOLTclv ttK dHzO distilled water DI DNA index DNA deoxyribonucleic acid Dsh dishevelled ES cell embryonic stem cell FAP familial adenomatous polyposis FCM flow cytometry GSK3-P glycogen synthase kinase 3-p hDLG human homologue of the Drosophila discs large tumour suppressor HMPS hereditary mixed polyposis syndrome HNPCC hereditary nonpolyposis colorectal cancer IPS juvenile polyposis syndrome kb kilo base pairs LOH loss of heterozygosity LRP low-density lipoprotein receptor-related protein mb mega base pairs MCR mutation cluster region MLHl human homologue of E. coli MutL MMR mismatch repair MSH2 human homologue of E. coli MutS MSI microsatellite instability MTHl human homologue of E. coli MutT MYH human homologue of E. coli MutY nm nanometer NSAID nonsteroidal anti-inflammatory drug nt nucleotides OGGI human homologue of E. coli MutM 8-oxo-G 8-oxo-7,8-dihydroxy-2'-deoxyguanosine PCR polymerase chain reaction PI propidium iodide PJS Peutz-Jeghers syndrome PMS2 human homologue of S. cerevisiae postmeiotic segregation increased PPAR peroxisome proliferator-activated receptor PTEN phosphatase and tensin homologue deleted on chromosome 10 PTT protein truncation test RNA ribonucleic acid ROS reactive oxygen species rpm rotations per minute RQM-PCR real-time quantitative multiplex PCR R-SMAD receptor-regulated SMAD SMAD human homologue of Drosophila small mothers against decapentaplegic SSCP single-strand conformation polymorphism TCP T cell factor TGF-p transforming growth factor-^ p-TRCP P-transducin repeat-containing protein All genes have been italicised throughout the text, whereas proteins are shown in plain text. Table of Contents Abstract.............................................................................................................................2 Acknowledgements.......................................................................................................... 3 Abbreviations ...................................................................................................................4 Table of Contents.............................................................................................................6 Table of Figures.............................................................................................................10 Table of Tables...............................................................................................................12 Chapter 1 Introduction to Colorectal Cancer .....................................................14 1.1 The Epidemiology of Colorectal Cancer ...........................................................14 1.2 The Natural History of Colorectal Cancer ....................................................... 17 1.2.1 The Anatomy of the Colorectum ...............................................................17 1.2.2 Adenomatous Polyps ..................................................................................19 1.2.3 Hamartomatous Polyps..............................................................................21 1.2.4 Stages of Colorectal Cancer...................................................................... 22 1.3 The Adenoma-Carcinoma Sequence .................................................................23 1.4 Hereditary Colorectal Cancer Syndromes ........................................................26 1.4.1 Polyposis Syndromes ................................................................................. 27 1.4.1.1 Familial Adenomatous Polyposis ..........................................................27 1.4.1.1.1 The APC Gene and its Functions ...................................................29 1.4.1.1.2 APC and the Regulation of Wnt Signalling .................................. 32 1.4.1.1.3 Germline Mutations in the APC Gene ........................................... 35 1.4.1.1.4 Genotype-phenotype Associations in FAP ....................................36 1.4.1.1.5 Somatic Mutations in the APC Gene ............................................ 37 1.4.1.1.6 Associations between Germline and Somatic APC Mutations.... 38 1.4.1.1.7 Genetic Testing and Clinical Management .................................. 39 1.4.1.2 Attenuated Adenomatous Polyposis Coli ...............................................40 1.4.1.2.1 APC Missense Variants and AAPC ..............................................41 1.4.1.2.2 Clinical Management ..................................................................... 42 1.4.1.3 Juvenile Polyposis ...................................................................................42 1.4.1.3.1 The TGF-(3/BMP Signalling Pathway...........................................44 6 1.4.1.4 Peutz-Jeghers Syndrome ........................................................................ 46 1.4.1.5 Cowden’s Syndrome and Bannayan-Riley-Ruvalcaba Syndrome.... 48 1.4.1.6 Hereditary Mixed Polyposis Syndrome ...............................................
Load more

Recommended publications
  • Migration of Jews to Palestine in the 20Th Century
    Name Date Migration of Jews to Palestine in the 20th Century Read the text below. The Jewish people historically defined themselves as the Jewish Diaspora, a group of people living in exile. Their traditional homeland was Palestine, a geographic region on the eastern coast of the Mediterranean Sea. Jewish leaders trace the source of the Jewish Diaspora to the Roman occupation of Palestine (then called Judea) in the 1st century CE. Fleeing the occupation, most Jews immigrated to Europe. Over the centuries, Jews began to slowly immigrate back to Palestine. Beginning in the 1200s, Jewish people were expelled from England, France, and central Europe. Most resettled in Russia and Eastern Europe, mainly Poland. A small population, however, immigrated to Palestine. In 1492, when King Ferdinand and Queen Isabella expelled all Jewish people living in Spain, some refugees settled in Palestine. At the turn of the 20th century, European Jews were migrating to Palestine in large numbers, fleeing religious persecution. In Russia, Jewish people were segregated into an area along the country’s western border, called the Pale of Settlement. In 1881, Russians began mass killings of Jews. The mass killings, called pogroms, caused many Jews to flee Russia and settle in Palestine. Prejudice against Jews, called anti-Semitism, was very strong in Germany, Austria-Hungary, and France. In 1894, a French army officer named Alfred Dreyfus was falsely accused of treason against the French government. Dreyfus, who was Jewish, was imprisoned for five years and tried again even after new information proved his innocence. The incident, called The Dreyfus Affair, exposed widespread anti-Semitism in Western Europe.
    [Show full text]
  • The Hebrew Revolution and the Revolution of the Hebrew Language Between the 1880S and the 1930S
    The Hebrew Revolution and the Revolution of the Hebrew Language between the 1880s and the 1930s Judith Winther Copenhagen The new Hebrew culture which began to crys- Eliezer Ben Yehudah was born in 1858, tallize in the land of Israel from the end of the Ben Gurion in 1886, and Berl Kazenelson in last century, is a successful event of "cultural 1887. planning". During a relatively short period of As a man who was not active in the so- time a little group of"culture planners" succee- cialist Jewish movement Ben Yehudah's dedi- ded in creating a system which in a significant cation to Hebrew is probably comprehensible. way was adapted to the requested Zionist ide- But why should a prominent socialist like Berl ology. The fact that the means by which the Kazenelson stick to the spoken Hebrew langu- "cultural planning" was realized implicated a age? A man, who prior to his immigration to heroic presentation of the happenings that led Palestine was an anti-Zionist, ridiculed Hebrew to a pathetical view of the development. It and was an enthusiastic devotee of Yiddish? presented the new historical ocurrences in Pa- The explanation is to be found in the vi- lestine as a renaissance and not as a continu- tal necessity which was felt by the pioneers ation of Jewish history, as a break and not as of the second Aliyah to achieve at all costs a continuity of the past. break from the past, from the large world of the The decision to create a political and a Russian revolutionary movements, from Rus- Hebrew cultural renaissance was laid down by sian culture, and Jewish Russian culture.
    [Show full text]
  • The Sephardim of the United States: an Exploratory Study
    The Sephardim of the United States: An Exploratory Study by MARC D. ANGEL WESTERN AND LEVANTINE SEPHARDIM • EARLY AMERICAN SETTLEMENT • DEVELOPMENT OF AMERICAN COMMUNITY • IMMIGRATION FROM LEVANT • JUDEO-SPANISH COMMUNITY • JUDEO-GREEK COMMUNITY • JUDEO-ARABIC COMMUNITY • SURVEY OF AMERICAN SEPHARDIM • BIRTHRATE • ECO- NOMIC STATUS • SECULAR AND RELIGIOUS EDUCATION • HISPANIC CHARACTER • SEPHARDI-ASHKENAZI INTERMARRIAGE • COMPARISON OF FOUR COMMUNITIES INTRODUCTION IN ITS MOST LITERAL SENSE the term Sephardi refers to Jews of Iberian origin. Sepharad is the Hebrew word for Spain. However, the term has generally come to include almost any Jew who is not Ashkenazi, who does not have a German- or Yiddish-language background.1 Although there are wide cultural divergences within the Note: It was necessary to consult many unpublished sources for this pioneering study. I am especially grateful to the Trustees of Congregation Shearith Israel, the Spanish and Portuguese Synagogue in New York City, for permitting me to use minutes of meetings, letters, and other unpublished materials. I am also indebted to the Synagogue's Sisterhood for making available its minutes. I wish to express my profound appreciation to Professor Nathan Goldberg of Yeshiva University for his guidance throughout every phase of this study. My special thanks go also to Messrs. Edgar J. Nathan 3rd, Joseph Papo, and Victor Tarry for reading the historical part of this essay and offering valuable suggestions and corrections, and to my wife for her excellent cooperation and assistance. Cecil Roth, "On Sephardi Jewry," Kol Sepharad, September-October 1966, pp. 2-6; Solomon Sassoon, "The Spiritual Heritage of the Sephardim," in Richard Barnett, ed., The Sephardi Heritage (New York, 1971), pp.
    [Show full text]
  • Abraham•S Children in the Genome Era: Major Jewish Diaspora
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector ARTICLE Abraham’s Children in the Genome Era: Major Jewish Diaspora Populations Comprise Distinct Genetic Clusters with Shared Middle Eastern Ancestry Gil Atzmon,1,2,6 Li Hao,3,6,7 Itsik Pe’er,4,6 Christopher Velez,3 Alexander Pearlman,3 Pier Francesco Palamara,4 Bernice Morrow,2 Eitan Friedman,5 Carole Oddoux,3 Edward Burns,1 and Harry Ostrer3,* For more than a century, Jews and non-Jews alike have tried to define the relatedness of contemporary Jewish people. Previous genetic studies of blood group and serum markers suggested that Jewish groups had Middle Eastern origin with greater genetic similarity between paired Jewish populations. However, these and successor studies of monoallelic Y chromosomal and mitochondrial genetic markers did not resolve the issues of within and between-group Jewish genetic identity. Here, genome-wide analysis of seven Jewish groups (Iranian, Iraqi, Syrian, Italian, Turkish, Greek, and Ashkenazi) and comparison with non-Jewish groups demonstrated distinctive Jewish population clusters, each with shared Middle Eastern ancestry, proximity to contemporary Middle Eastern populations, and variable degrees of European and North African admixture. Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry.
    [Show full text]
  • The Role of Envy in Anti-Semitism by José Leopoldo Duarte A
    The Role of Envy in Anti-Semitism by José Leopoldo Duarte A Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy Approved April 2015 by the Graduate Supervisory Committee Adam Cohen, Chair Steven L. Neuberg Paul Karoly Craig T. Nagoshi ARIZONA STATE UNIVERSITY December 2015 ABSTRACT Anti-Semitism is a recurrent phenomenon in modern history, but has garnered relatively little focus among research psychologists compared to prejudice toward other groups. The present work frames anti-Semitism as a strategy for managing the implications of Jews’ extraordinary achievements compared to other groups. Anti- Semitic beliefs are sorted into two types: stereotypes that undercut the merit of Jews’ achievements by attributing them to unfair advantages such as power behind the scenes; and stereotypes that offset Jews’ achievements by attaching unfavorable traits or defects to Jews, which are unrelated to the achievement domains, e.g. irritating personalities or genetically-specific health problems. The salience of Jews’ disproportionate achievements was hypothesized as driving greater endorsement of anti-Semitic stereotypes, and envy was hypothesized as mediating this effect. Individual differences in narcissistic self-esteem and moral intuitions around in- group loyalty and equity-based fairness were hypothesized as moderating the effect of Jewish achievement on anti-Semitic beliefs. The results showed greater endorsement of undercutting – but not offsetting – stereotypes after reading about Jewish achievements, compared to Jewish culture or general American achievement conditions. Envy did not significantly mediate this effect. The moral foundation of in- group loyalty predicted greater endorsement of anti-Semitic stereotypes in the Jewish Achievement condition, and lesser endorsement in the Jewish Culture condition.
    [Show full text]
  • The Memorial Inscription from the Bimah of the Great Synagogue of Vilna
    Article Between Yerushalayim DeLita and Jerusalem— The Memorial Inscription from the Bimah of the Great Synagogue of Vilna Jon Seligman Israel Antiquities Authority, Jerusalem 91004, Israel; [email protected] Received: 19 February 2020; Accepted: 18 March 2020; Published: 1 April 2020 Abstract: During excavations of the bimah (the platform for reading the Torah) of the 17th-century Great Synagogue of Vilna (Vilnius, Lithuania), an important memorial inscription was exposed. This paper describes the new finds associated with the baroque-rococo architecture of the bimah and focuses on the inscription and its meaning. The Hebrew inscription, engraved on a large stone slab, is a complex rabbinic text filled with biblical allusions, symbolism, gematria, and abbreviations. The text describes the donation of a Torah reading table in 1796 in honour of R. Ḥayim ben Ḥayim and of Sarah by their sons, R. Eliezer and Shmuel. The inscription notes the aliyah (emigration) of Ḥayim and Sarah to Eretz Israel, the Land of Israel. The interpretation of the inscription shows the use of multiple messianic motifs. Historical analysis identifies the involvement of the Vilna community with the support of the Yishuv (the Jewish community in Ottoman Palestine) and the aliyah of senior scholars and community leaders at the end of the 18th and early 19th centuries. Amongst these figures were Ḥayim ben Ḥayim and Sarah, with Ḥayim ben Ḥayim going on to represent the Vilna community in the Land of Israel as its emissary, distributing charitable donations to the scholarly Ashkenazi community resident in Tiberias, Safed, and later Jerusalem. Keywords: Vilna/Vilnius; synagogue; bimah; inscription; Jerusalem; aliyah Over the past five years (2016–2019), a consortium of researchers 1 has been conducting archaeological research on the site of the Great Synagogue and Shulhoyf (synagogue courtyard) of Vilna (present-day Vilnius in Lithuania).
    [Show full text]
  • Name Fluidity and Its Effect on Ashkenazi Genealogical Research
    Dominican Scholar Senior Theses Student Scholarship 5-2019 Name Fluidity and its Effect on Ashkenazi Genealogical Research Meredith Dreyfuss Dominican University of California https://doi.org/10.33015/dominican.edu/2019.HCS.ST.05 Survey: Let us know how this paper benefits you. Recommended Citation Dreyfuss, Meredith, "Name Fluidity and its Effect on Ashkenazi Genealogical Research" (2019). Senior Theses. 114. https://doi.org/10.33015/dominican.edu/2019.HCS.ST.05 This Senior Thesis is brought to you for free and open access by the Student Scholarship at Dominican Scholar. It has been accepted for inclusion in Senior Theses by an authorized administrator of Dominican Scholar. For more information, please contact [email protected]. Meredith Dreyfuss HCS 4910 Senior Capstone Project Instructor: Dr. Chase Clow Reader: Robert Bradford Name Fluidity and its Effect on Ashkenazi Genealogical Research It is commonly believed that genealogical research has become easier and more popular than ever before, and with more and more records being digitized and available over the internet, the ability to research family history can be done by anyone with an interest and a computer. Where one might have had to travel to the places that housed the records that trace family life, now many of those records are online, with the data store growing all the time. Similarly, relatively inexpensive DNA testing is bringing family background and history to the masses. However, while science and technology have revolutionized genealogical research, it can still be very difficult to research one’s family history. Specifically, for Ashkenazi Jews, those from Central and Eastern Europe, there is a history of name changes, both given and surname, which makes the search for one’s ancestors a difficult challenge.
    [Show full text]
  • Jewish Emancipation and Schism: Economic Development and Religious Change ∗
    Jewish Emancipation and Schism: Economic Development and Religious Change ∗ Jean-Paul Carvalho Mark Koyama University of California, Irvine George Mason University June 17, 2016 Abstract This paper studies the impact of Jewish Emancipation and economic develop- ment on Jewish religious culture in 19th century Europe. In Germany, a liberal Reform movement developed in response to emancipation, while ultra-Orthodox Judaism emerged in eastern Europe. We develop a historical narrative and model of religious organization that accounts for the polarized responses by Jewish com- munities. Our explanation is based on a tradeoff between time and money contri- butions. A religious organization chooses between a relatively affluent community that expends little effort on religious participation and a poorer community that devotes a large amount of time and effort to religious activity. Political and economic development shape this tradeoff in unexpected ways, leading to com- plex forms of behavior such as religious schisms and cycles. When preferences are transmitted intergenerationally, organizations tend to be more conservative. Our historical narrative points to further extensions of extant models of religion, as well as providing broader insights into cultural integration and religious change. JEL Classification: D23, N33, Z12, J24 Keywords: economics of religion, club goods, community, economic development ∗Carvalho: Department of Economics, University of California, Irvine, 3151 Social Science Plaza, Irvine, CA 92697, [email protected]. Koyama: Center for Public Choice, Carow Hall, George Mason University, VA 22030, [email protected]. We thank the editor and two anonymous referees for their comments. We are grateful for valuable conversa- tions with Eli Berman, Lloyd Cohen, Tyler Cowen, Stephan Funk, Noel Johnson, Tom Klein, Mike McBride, Avner Offer, Francis Teal, Jared Rubin, Gaston Yalonetzky and Peyton Young.
    [Show full text]
  • Congregation Shaar Hashomayim
    Congregation Shaar Hashomayim. View from Côte-Saint-Antoine Road The nave, looking towards the bimah Photo: Bergeron Gagnon inc. Photo: Bergeron Gagnon inc. THE HERITAGE VALUE STATEMENT CONGREGATION SHAAR HASHOMAYIM CIVIC ADDRESS HERITAGE DESIGNATION RELIGIOUS DENOMINATION 450 Kensington Avenue, Westmount Municipal - Category 1: Important ? Jewish ? Ashkenazi traditional Original 1922 Synagogue (SPAIP) (Orthodox) rite - Category 2: Interesting ? 1948 and 1967 Additions (SPAIP) Provincial - None Federal - None OVERVIEW Historical Value The historical heritage value resides in the history of the Shaar Hashomayim congregation with Westmount since 1922, when the present synagogue was built. It is the oldest Ashkenazi synagogue in Canada and has, for the last hundred years, had a leadership role nationally and internationally in issues affecting the Jewish community and in larger ones of social justice. The sacrifice of the membership during both World Wars is commemorated in its memorials. The long history of the membership can be traced through the individual memorial plaques. The museum contains a large collection of Judaica and artefacts related to the history of Jewish life in Montreal. The synagogue also has a significant collection of portraits and artwork. The Shaar is famous for the quality of its music, which is an integral part of its religious services. In recent memory, the congregation, its cantor and choir have become associated with Leonard Cohen?s last musical compositions. Contextual Value The contextual heritage value resides in the synagogue?s large footprint which, with its associated buildings, occupies almost an entire city block. It is a landmark within a residential community and also forms part of the institutional heart of Westmount.
    [Show full text]
  • A Tradition Without a Past
    Chapter 8 A Tradition without a Past A new hope sprang up in the 1980s – the promise to realize and establish the Mizrahi communities in Israel as an integral part of Israeli society, destined to reclaim the focus of its oriental traditions and history and reclaim its shattered dignity: “Restoring the past glory.” This was the foundation for a new politi- cal party, Shas, comprised purely of Mizrahi members, or Sephardim, as they referred to themselves. The party ran its first campaign in the 1983 municipal elections with the intention of later running independently. Most members and supporters were descendants of North African families,1 spiritually awak- ened after the religious revival of the mid-‘70s and led by Rabbis Reuven Elbaz (Morocco) and Amnon Yitzhak (Yemen). They followed the Iraqi traditions and the teachings of the Rishon Lezion, the former Sephardi Chief Rabbi of Israel, and Rabbi Ovadia Yosef (Iraq). Shas was founded by Jerusalemite Sephardim in their 30s,2 men who had experienced firsthand cultural and social discrimina- tion from their Ashkenazi peers.3 The Mizrahim forged a new path, not to spite religion or the ultraorthodox Ashkenazi culture, but as a way of “politicizing integrative religious awareness […] with an electoral manifestation.”4 They claimed to have been disappointed and hurt by the Mizrahi wing of the Agudat Israel party (Hasidim), and later by the behavior of Lithuanian ultraorthodox leader Rabbi Schach towards Rabbi Ovadia Yosef. Their response was to form a party that would attract not only the Haredi-Sephardi
    [Show full text]
  • AJC's Glossary of Antisemitic Terms, Phrases, Conspiracies, Cartoons, Themes, and Memes
    American Jewish Committee AJC's glossary of antisemitic terms, phrases, conspiracies, cartoons, themes, and memes. American Jewish Committee | The Translate Hate Glossary | November 2019 1 Table of Contents Introduction 3 I Illuminati 10 B blood libel 4 J Jew down 10 “Jewish features” 10 C Jewish figures 11 clannish 4 conspiracy theory 5 control 5 K Khazars 11 cowardice 6 kosher tax 12 creatures 6 N D New World Order 13 dual loyalty 6 P E Protocols of the Elders of Zion 13 (((echo))) 7 S G scapegoat 14 globalist 8 silencing 14 “The Goyim Know” 8 smirking merchant 15 greed 9 Z H Zionist 15 Holocaust denial 9 How to Report Hate 16 Conclusion 16 2 The Translate Hate Glossary Antisemitism is the hatred of Jews. But it manifests itself in so many ways. It includes medieval blood libel claims rooted in Christianity and twentieth century conspiracy theories about Jewish control of the world economy. It encompasses Holocaust denial and distortion and virulent anti-Israel animus. It can exist in places where Jews are prominent and visible and in places where Jews themselves are entirely absent. It may be present in physical encounters at work or on the street or in the virtual world of the internet and social media. But in order to combat antisemitism we must first understand it. And that means we must define it in all its forms and expressions, in ways both painfully evident and obscure. This glossary offers a comprehensive list of terms and expressions that will help you recognize antisemitism when you see it.
    [Show full text]
  • Who Is the Synagogue of Satan (Pdf) Download
    Who is the Synagogue of Satan 1. Revelation 2:8-9 2. Revelation 3:9 3. Genesis 9:20-29 (Ashkenazi Jews I.E. Gentile Converts) ● The word enlarge here is not the best translation. The KJV translates Strong's H6601 in the following manner: entice (10x), deceive (8x), persuade (4x), flatter pâthâh, paw-thaw'; a ָפּ ָתה .(2x), allure (1x), enlarge (1x), silly one (1x), silly (1x) primitive root; to open, i.e. be (causatively, make) roomy; usually figuratively (in a mental or moral sense) to be (causatively, make) simple or (in a sinister way) delude:—allure, deceive, enlarge, entice, flatter, persuade, silly (one). Yah enticed Japheth to dwell in the tents in the tents of Shem (the promised land). This happened during the crusades, 1949, & will again after the abomination of desolation. 4. Genesis 10:1-5 ● Encylopedia Brittanica: Ashkenazi, plural Ashkenazim, from Hebrew Ashkenaz ​ ​ (“Germany”), member of the Jews who lived in the Rhineland valley and in neighbouring France before their migration eastward to Slavic lands (e.g., Poland, Lithuania, Russia) after the Crusades (11th–13th century) and their descendants. After the 17th-century persecutions in eastern Europe, large numbers of these Jews resettled in western Europe, where they assimilated, as they had done in eastern Europe, with other Jewish communities. In time, all Jews who had adopted the “German rite” synagogue ritual were referred to as Ashkenazim to distinguish them from Sephardic (Spanish rite) Jews. Ashkenazim differ from Sephardim in their pronunciation of Hebrew, in cultural traditions, in synagogue cantillation (chanting), in their widespread use of Yiddish (until the ​ 20th century), and especially in synagogue liturgy.
    [Show full text]