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Concept: Jews

326

The question of Jewish ancestry has been the subject of controversy for over two centuries and has yet to be resolved. The “Rhineland Hypothesis” depicts Eastern European Jews as a “population isolate” that emerged from a small group of German Jews who migrated eastward and expanded rapidly. Alternatively, the “Khazarian Hypothesis” suggests that Eastern European Jew descended from the Khazars, an amalgam of Turkic clans that settled the Caucasus in the early centuries CE and converted to Judaism in the 8(th) century. Mesopotamian and Greco-Roman Jews continuously reinforced the Judaized Empire until the 13(th) century. Following the collapse of their empire, the Judeo-Khazars fled to Eastern Europe. The rise of European Jewry is therefore explained by the contribution of the Judeo-Khazars. Thus far, however, the Khazar’s contribution has been estimated only empirically, as the absence of genome-wide data from Caucasus populations precluded testing the Khazarian Hypothesis. Recent sequencing of modern Caucasus populations prompted us to revisit the Khazarian Hypothesis and compare it with the Rhineland Hypothesis. We applied a wide range of population genetic analyses to compare these two hypotheses. Our findings support the Khazarian Hypothesis and portray the European Jewish genome as a mosaic of Caucasus, European, and Semitic ancestries, thereby consolidating previous contradictory reports of Jewish ancestry. We further describe major difference among Caucasus populations explained by early presence of Judeans in the Southern and Central Caucasus. Our results have important implications on the demographic forces that shaped the genetic diversity in the Caucasus and medical studies.

Concepts: Germany, Jews, Judaism, Russia, Soviet Union, Jewish ethnic divisions, Hebrew language, Ashkenazi Jews

163

The I405V polymorphism of the cholesteryl ester transfer protein gene (CETP) has been suggested to be a protective factor conferring longevity in Ashkenazi Jews, although findings in other races are not supportive. This paper describes a case-control study and a meta-analysis conducted to derive a more precise estimation of the association between CETP 405V and longevity.

Concepts: DNA, Gene, Allele, Cholesterylester transfer protein, Cholesteryl ester, Jews, Jewish ethnic divisions, Ashkenazi Jews

128

MacDonald argues that a suite of genetic and cultural adaptations among Jews constitutes a “group evolutionary strategy.” Their supposed genetic adaptations include, most notably, high intelligence, conscientiousness, and ethnocentrism. According to this thesis, several major intellectual and political movements, such as Boasian anthropology, Freudian psychoanalysis, and multiculturalism, were consciously or unconsciously designed by Jews to (a) promote collectivism and group continuity among themselves in Israel and the diaspora and (b) undermine the cohesion of gentile populations, thus increasing the competitive advantage of Jews and weakening organized gentile resistance (i.e., anti-Semitism). By developing and promoting these movements, Jews supposedly played a necessary role in the ascendancy of liberalism and multiculturalism in the West. While not achieving widespread acceptance among evolutionary scientists, this theory has been enormously influential in the burgeoning political movement known as the “alt-right.” Examination of MacDonald’s argument suggests that he relies on systematically misrepresented sources and cherry-picked facts. It is argued here that the evidence favors what is termed the “default hypothesis”: Because of their above-average intelligence and concentration in influential urban areas, Jews in recent history have been overrepresented in all major intellectual and political movements, including conservative movements, that were not overtly anti-Semitic.

Concepts: Genetics, Evolution, Politics, Jews, Judaism, Psychoanalysis, Antisemitism, Social movement

106

The Yiddish language is over one thousand years old and incorporates German, Slavic, and Hebrew elements. The prevalent view claims Yiddish has a German origin, whereas the opposing view posits a Slavic origin with strong Iranian and weak Turkic substrata. One of the major difficulties in deciding between these hypotheses is the unknown geographical origin of Yiddish speaking Ashkenazic Jews (AJs). An analysis of 393 Ashkenazic, Iranian, and mountain Jews and over 600 non-Jewish genomes demonstrated that Greeks, Romans, Iranians, and Turks exhibit the highest genetic similarity with AJs. The Geographic Population Structure (GPS) analysis localized most AJs along major primeval trade routes in northeastern Turkey adjacent to primeval villages with names that may be derived from “Ashkenaz.” Iranian and mountain Jews were localized along trade routes on the Turkey’s eastern border. Loss of maternal haplogroups was evident in non-Yiddish speaking AJs. Our results suggest that AJs originated from a Slavo-Iranian confederation, which the Jews call “Ashkenazic” (i.e., “Scythian”), though these Jews probably spoke Persian and/or Ossete. This is compatible with linguistic evidence suggesting that Yiddish is a Slavic language created by Irano-Turko-Slavic Jewish merchants along the Silk Roads as a cryptic trade language, spoken only by its originators to gain an advantage in trade. Later, in the 9th century, Yiddish underwent relexification by adopting a new vocabulary that consists of a minority of German and Hebrew and a majority of newly coined Germanoid and Hebroid elements that replaced most of the original Eastern Slavic and Sorbian vocabularies, while keeping the original grammars intact.

Concepts: Jews, Judaism, Jewish ethnic divisions, Hebrew language, Ashkenazi Jews, Yiddish language, Jewish languages, Haskalah

52

Adherents to the Jewish faith have resided in numerous geographic locations over the course of three millennia. Progressively more detailed population genetic analysis carried out independently by multiple research groups over the past two decades has revealed a pattern for the population genetic architecture of contemporary Jews descendant from globally dispersed Diaspora communities. This pattern is consistent with a major, but variable component of shared Near East ancestry, together with variable degrees of admixture and introgression from the corresponding host Diaspora populations. By combining analysis of monoallelic markers with recent genome-wide variation analysis of simple tandem repeats, copy number variations, and single-nucleotide polymorphisms at high density, it has been possible to determine the relative contribution of sex-specific migration and introgression to map founder events and to suggest demographic histories corresponding to western and eastern Diaspora migrations, as well as subsequent microevolutionary events. These patterns have been congruous with the inferences of many, but not of all historians using more traditional tools such as archeology, archival records, linguistics, comparative analysis of religious narrative, liturgy and practices. Importantly, the population genetic architecture of Jews helps to explain the observed patterns of health and disease-relevant mutations and phenotypes which continue to be carefully studied and catalogued, and represent an important resource for human medical genetics research. The current review attempts to provide a succinct update of the more recent developments in a historical and human health context.

Concepts: DNA, Genetics, Evolution, Biology, Population genetics, Jews, Judaism, Gene flow

28

Using the historical population of Gibraltar to examine the pattern of mortality of Jews and Roman Catholics revealed that: (1) the Jews exhibited a significantly better health status as measured by life expectancy at birth (47.66 and 47.56 for Jewish males and females vs. 38.10 and 40.89 for Catholics males and females, respectively), (2) most of the disparity is found in the very young age categories and (3) the significantly lower rates of deaths could be attributed to the diarrheal and nutritional complex. Stage two of the research involved the linkage of deaths over a 7-year period relative to their household context as of 1878. Being Jewish, having a servant, having access to a water well in the tenement and residing in a tenement only with other Jews, were all factors that contributed to a higher life expectancy. Our explanation for the enhanced survivorship among the Jews is grounded in economics as well as in an established welfare system, in religious precepts and in secular knowledge of health. One of the more notable and hitherto unobserved findings is that Roman Catholics residing in the same tenements with Jews enjoyed a distinct health advantage. This suggests that a positive amplification effect arose from their co-residence with the Jews.

Concepts: Demography, Population, Middle Ages, Life expectancy, Jews, Judaism, Ashkenazi Jews, Who is a Jew?

28

The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn’s disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at NOD2, in which three causal, uncommon and conditionally independent NOD2 variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with P-value <10(-3), respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established CD loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in TRPM2 on chromosome 21. Within the chromosome 16 region, R642S of HEATR3 and rs9922362 of BRD7 showed genome-wide significance. Expression studies of HEATR3 demonstrated a positive role in NOD2-mediated NF-κB signaling. The BRD7 signal showed conditional dependence with only the downstream rare CD-causal variants in NOD2, but not with the background haplotype; this elaborates NOD2 as a key illustration of synthetic association.Genes and Immunity advance online publication, 25 April 2013; doi:10.1038/gene.2013.19.

Concepts: Gene, Mutation, Chromosome, Genetic genealogy, Chromosomes, Jews, Jewish ethnic divisions, Ashkenazi Jews

28

Ultra-orthodox Jews compose a segregated group that struggles to preserve its centuries-old way of life by strictly adhering to the Jewish religious law in every aspect of life. Their health habits were infrequently studied to date. We sought to determine the smoking prevalence and to find its significant correlates in the ultra-orthodox Jewish population of Israel.

Concepts: Cigarette, Israel, Jews, Judaism, Jewish ethnic divisions, Halakha, Zionism, Jewish population

27

INTRODUCTION: Percent mammographic density (PMD) adjusted for age and BMI is one of the strongest risk factors for breast cancer and is known to be approximately 60 percent heritable. Here we report a finding of an association between genetic ancestry and adjusted PMD. METHODS: We selected self-identified Caucasian women in the California Pacific Medical Center Research Institute Cohort whose screening mammograms placed them in the top or bottom quintiles of age- and body mass index-adjusted PMD. Our final data set included 474 women with the highest adjusted PMD and 469 with the lowest genotyped on the Illumina 1M platform. Principal component analysis (PCA) and identity-by-descent (IBD) analyses allowed us to infer the women’s genetic ancestry and correlate it with adjusted PMD. RESULTS: Women of Ashkenazi Jewish ancestry, as defined by the first principal component (PC1) of PCA and identity-by-descent analyses, represented approximately 15 percent of the sample. Ashkenazi Jewish ancestry, defined by PC1, was associated with higher adjusted PMD (p = 0.004). Using multivariate regression to adjust for epidemiologic factors associated with PMD, including age at parity and use of postmenopausal hormone therapy, did not attenuate the association. CONCLUSION: Women of Ashkenazi Jewish ancestry based on genetic analysis are more likely to have high age- and BMI-adjusted PMD. Ashkenazi Jews may have a unique set of genetic variants or environmental risk factors that increase mammographic density.

Concepts: Breast cancer, Jews, Judaism, Jewish ethnic divisions, Hebrew language, Ashkenazi Jews, Zionism, Who is a Jew?

27

Familial Mediterranean Fever (FMF) is an autosomal recessive disease that is widely spread in the populations of the Mediterranean region. It is characterized by recurrent fever and inflammatory attacks. A total of 1700 suspected patients, belonging to various communities in Israel: Jews (Ashkenazi and non-Ashkenazi), Arabs (Muslims and Christians) and Druze, was subjected to examination for FMF mutation screening. The patients were screened for the most common six MEFV gene mutations namely, M680I, M694V, M694I, V726A, E148Q and K695R. Fifty five percent of the cases were confirmed to have MEFV mutations. The most common mutations among all the cases studied were M694V, E148Q and V726A. The common mutations in the respective communities were: among the Jews M694V with a frequency of 69.9% (76.8% for non-Ashkenazi Jews and 43.6% for Ashkenazi Jews), among the Arabs V726A with a frequency of 32.7% (32.7% for Muslims and 32.1% for Christians) and among Druze it was E148Q with a frequency of 52.1%. The characteristic mutation present in Jews was K695R and the one in Arabs was M680I, while no characteristic mutation was found in Druze. On the other hand, mutation E148Q was observed to have a considerable occurrence in patients of all ethnic groups studied. Furthermore, our results revealed that homozygous mutations accounted for 168 cases (18%). The homozygote mutation M694V was the most prevalent among Jews and the E148Q mutation was the most common among Druze, while, among Arabs there were three homozygous mutations having maximum prevalence, namely, V726A, M694V and M694I. Our study comprehensively provided a spectrum of FMF mutations in various communities of Israeli society.

Concepts: Mutation, Mediterranean Sea, Familial Mediterranean fever, Israel, Jews, Judaism, Jewish ethnic divisions, Ashkenazi Jews