Genetic affinities of Jewish populations.

Genetic relations between various Jewish (J) and non-Jewish (NJ) populations were assessed using two sets of data. The first set contained 12 pairs of matched J and NJ populations from Europe, the Middle East, and North Africa, for which 10 common polymorphic genetic systems (13 loci) were available. The second set included 22 polymorphic genetic systems (26 loci) with various numbers of populations (ranging from 21 to 51) for each system. Therefore, each system was studied separately. Nei's standard genetic distance (D) matrices obtained for these two sets of data were tested against design matrices specifying hypotheses concerning the affiliations of the tested populations. The tests against single designs were carried out by means of Mantel tests. Our results consistently show lower distances among J populations than with their NJ neighbors, most simply explained by the common origin of the former. Yet, there is evidence also of genetic similarity between J and corresponding NJ populations, suggesting reciprocal gene flow between these populations or convergent selection in a common environment. The results of our study also indicate that stochastic factors are likely to have played a role in masking the descent relationships of the J populations.     

The Tay-Sachs disease gene in North American Jewish populations: geographic variations and origin.

From data collected in a North American Tay-Sachs disease (TSD) heterozygote screening program, the TSD carrier frequency among 46,304 Jewish individuals was found to be .0324 (1 in 31 individuals). This frequency is consistent with earlier estimates based on TSD incidence data. TSD carrier frequencies were then examined by single country and single region of origin in 28,029 Jews within this sample for whom such data were available for analysis. Jews with Polish and/or Russian ancestry constituted 88% of this sample and had a TSD carrier frequency of .0327. No TSD carriers were observed among the 166 Jews of Near Eastern origins. Relative to Jews of Polish and Russian origins, there was at least a twofold increase in the TSD carrier frequency in Jews of Austrian, Hungarian, and Czechoslovakian origins (P less than .005). These findings suggest that the TSD gene proliferated among the antecedents of modern Ashkenazi Jewry after the Second Diaspora (70 A.D.) and before their major migrations to regions of Poland and Russia (before 1100 A.D.).     

Hypodontia: Prevalence amongst Jewish populations of different origin

The teeth of 10,371 male and 11,013 female Israel Jews were examined. Prevalence of all hypodontia was 4.60% with no significant difference between the sexes; 2.11% lacked upper lateral incisors, the females having a significantly higher prevalence than males. Second premolars were missing in 1.87% of the population, with no significant differences between the sexes. Missing lower incisors was diagnosed in 0.68% of the children, with a higher prevalence in males. Prevalence of missing lower incisors was similar in the Ashkenazi and in the non-Ashkenazi. The teeth most frequently missing in descending order were the upper lateral incisors and the lower second premolars.     

Immunoglobulin allotypes in Jewish populations living in Israel and the United States

The ongoing interest in the interrelationships of Jewish populations justifies inclusion of the immunoglobulin allotypes in an ethnohistorical analysis. A total of 2,184 serum specimens obtained from unrelated Israeli Jewish and self-identified Milwaukee, WI, Jewish blood donors were classified as Ashkenazi, Sephardi, Asiatic, or North African and tested for G1m (a, x, z, and f), G3m (b0, b1, b3, b5, g), A2m (1 and 2), and Km (1). Selected sera were also tested for G3m (s, t, c3, c5). The estimated maximum likelihood Gm-Am haplotype frequencies were used in a heterogeneity chi-square analysis. The results indicate that there is less heterogeneity within Jewish populations from Europe, Middle East, and North Africa than in corresponding non-Jewish populations representing the same geographical areas. In order to avoid the hazards of a univariate focus, previously published data were incorporated into two additional analyses: 15 populations with information on 16 genetic loci and 24 populations with information on five genetic loci. Both sets of data were analyzed using principal-components and cluster analysis. In both sets of analyses, with the exception of the Yemenite Jews, Jewish populations grouped together. These analyses support the belief that Jewish populations appear to be derived from a common gene pool, and there has been some genetic drift and minimal gene flow with surrounding populations.     

Analysis of genetic data on Jewish populations. I. Historical background, demographic features, and genetic markers.

Part I describes the data sets on which the analysis of Part II is based. This covers the nature of the populations sampled, the extent to which the samples are representative, and a brief review of historical and demographic facts on the populations involved.     

Contrasting patterns of Y chromosome variation in Ashkenazi Jewish and host non-Jewish European populations

The molecular basis of more than 25 genetic diseases has been described in Ashkenazi Jewish populations. Most of these diseases are characterized by one or two major founder mutations that are present in the Ashkenazi population at elevated frequencies. One explanation for this preponderance of recessive diseases is accentuated genetic drift resulting from a series of dispersals to and within Europe, endogamy, and/or recent rapid population growth. However, a clear picture of the manner in which neutral genetic variation has been affected by such a demographic history has not yet emerged. We have examined a set of 32 binary markers (single nucleotide polymorphisms; SNPs) and 10 microsatellites on the non-recombining portion of the Y chromosome (NRY) to investigate the ways in which patterns of variation differ between Ashkenazi Jewish and their non-Jewish host populations in Europe. This set of SNPs defines a total of 20 NRY haplogroups in these populations, at least four of which are likely to have been part of the ancestral Ashkenazi gene pool in the Near East, and at least three of which may have introgressed to some degree into Ashkenazi populations after their dispersal to Europe. It is striking that whereas Ashkenazi populations are genetically more diverse at both the SNP and STR level compared with their European non-Jewish counterparts, they have greatly reduced within-haplogroup STR variability, especially in those founder haplogroups that migrated from the Near East. This contrasting pattern of diversity in Ashkenazi populations is evidence for a reduction in male effective population size, possibly resulting from a series of founder events and high rates of endogamy within Europe. This reduced effective population size may explain the high incidence of founder disease mutations despite overall high levels of NRY diversity.Electronic Supplementary Material Supplementary material is available in the online version of this article at D.M. Behar and D. Garrigan contributed equally to this workElectronic database information: URLs for the data in this article are as follows:ARLEQUIN,     

Y chromosome haplogroups and prostate cancer in populations of European and Ashkenazi Jewish ancestry

Genetic variation on the Y chromosome has not been convincingly implicated in prostate cancer risk. To comprehensively analyze the role of inherited Y chromosome variation in prostate cancer risk in individuals of European ancestry, we genotyped 34 binary Y chromosome markers in 3,995 prostate cancer cases and 3,815 control subjects drawn from four studies. In this set, we identified nominally significant association between a rare haplogroup, E1b1b1c, and prostate cancer in stage I (P = 0.012, OR = 0.51; 95% confidence interval 0.30-0.87). Population substructure of E1b1b1c carriers suggested Ashkenazi Jewish ancestry, prompting a replication phase in individuals of both European and Ashkenazi Jewish ancestry. The association was not significant for prostate cancer overall in studies of either Ashkenazi Jewish (1,686 cases and 1,597 control subjects) or European (686 cases and 734 control subjects) ancestry (P(meta) = 0.078), but a meta-analysis of stage I and II studies revealed a nominally significant association with prostate cancer risk (P(meta) = 0.010, OR = 0.77; 95% confidence interval 0.62-0.94). Comparing haplogroup frequencies between studies, we noted strong similarities between those conducted in the US and France, in which the majority of men carried R1 haplogroups, resembling Northwestern European populations. On the other hand, Finns had a remarkably different haplogroup distribution with a preponderance of N1c and I1 haplogroups. In summary, our results suggest that inherited Y chromosome variation plays a limited role in prostate cancer etiology in European populations but warrant follow-up in additional large and well characterized studies of multiple ethnic backgrounds.     

Analysis of biochemical genetic data on Jewish populations. III. The application of individual phenotype measurements for population comparisons.

Individual phenotypic data on six blood markers and six enzyme polymorphisms in seven Jewish and two non-Jewish populations were subjected to a comparative statistical analysis. A set of functionals defined with respect to the individual biochemical profiles was used to investigate the following problems: (1) What are the distributional characteristics of various types of individual heterozygosity measures (for blood and enzyme loci) within and across populations? (2) Is the observed phenotypic variation in agreement with what might be expected if the loci were independent? (3) What proportion of the characteristics can be explained by reference to population structure and historical data? Average total heterozygosity of blood and protein loci was highest in the Iraqi population and lowest in the Yemenite. The differences among the other populations were not significant. The highest cumulative recessive homozygosity of blood markers occurs in Yemenites and Samaritans. No association was present between total blood and protein heterozygosity. Applications of these ideas and techniques to the study of multilocus genetic organization are discussed.     

Characterization of two New York City Jewish populations at six short tandem repeat loci

The Hasidic and non-Hasidic Jewish communities of New York City represent two subpopulations with long-documented histories of restrictive marriage patterns and a high degree of endogamy. As part of a continuing study into their genetic structure, allele frequencies were determined for the six tetrameric short tandem repeat (STR) loci: FESFPS, F13AO1, vWA, CSF1PO, TPOX, and THO1. All loci were tested for Hardy-Weinberg equilibrium (HWE) by three tests: chi-square analysis, Monte Carlo chi-square analysis. and the exact test. The non-Hasidic population failed to meet HWE at the F13A01, FESFPS, and CSF1PO loci by all three tests. The Hasidic population also failed to meet HWE at the same loci by some of the tests. Comparison of the Hasidic to the non-Hasidic population using an R x C contingency table demonstrated a similarity at only the vWA locus. Significant differences exist when comparing the two Jewish populations to a reference Caucasian population.     

Bloom's syndrome in an Iranian Jewish male.

Bloom's syndrome is described in an Iranian Jewish male who subsequently developed myocardial disease. This may represent the first definitely non Ashkenazi Jewish patient in the literature and the only one to develop this complication.     

Sandhoff disease heterozygote detection: a component of population screening for Tay-Sachs disease carriers. II. Sandhoff disease gene frequencies in American Jewish and non-Jewish populations.

Carrier frequencies for the allele(s) causing Sandhoff disease have been estimated for the U.S. Jewish and non-Jewish populations. The estimates have been made directly, with data from 22,043 Jewish and 32,342 non-Jewish individuals measured for total serum hexosaminidase activity and the heat-labile fraction. These values have been shown to identify potential carriers of the Sandhoff allele(s) with 95% sensitivity. Subsequent leukocyte assays of total hexosaminidase activity and the heat-labile fraction in those identified in serum tests have been shown to provide a much finer discrimination between those who carry the allele(s) and those who do not. Results from such assays were used to generate these carrier frequency estimates. Carrier frequency estimates have also been made indirectly from Sandhoff disease incidence data collected during the period 1979-84. These estimates are in agreement with data for the Jewish population under analysis, but in the non-Jewish population the estimate derived from data on screened individuals is greater than the estimate derived from incidence figures. The possible causes for such a difference are discussed. In a study of non-Jewish individuals each of whose grandparents derives from a single country of origin, the distribution of countries among Sandhoff disease carriers differs significantly from that in the non-Jewish sample under analysis, indicating possible ethnic groups with increased or decreased carrier frequencies. These analyses suggest an increased Sandhoff disease carrier frequency among Mexican and Central-American populations and a decreased carrier frequency among non-Jewish German populations.     

Analysis of biochemical genetic data on Jewish populations: II. Results and interpretations of heterogeneity indices and distance measures with respect to standards.

A nonparametric statistical methodology is used for the analysis of biochemical frequency data observed on a series of nine Jewish and six non-Jewish populations. Two categories of statistics are used: heterogeneity indices and various distance measures with respect to a standard. The latter are more discriminating in exploiting historical, geographical and culturally relevant information. A number of partial orderings and distance relationships among the populations are determined. Our concern in this study is to analyze similarities and differences among the Jewish populations, in terms of the gene frequency distributions for a number of genetic markers. Typical questions discussed are as follows: These Jewish populations differ in certain morphological and anthropometric traits. Are there corresponding differences in biochemical genetic constitution? How can we assess the extent of heterogeneity between and within groupings? Which class of markers (blood typings or protein loci) discriminates better among the separate populations? The results are quite surprising. For example, we found the Ashkenazi, Sephardi and Iraqi Jewish populations to be consistently close in genetic constitution and distant from all the other populations, namely the Yemenite and Cochin Jews, the Arabs, and the non-Jewish German and Russian populations. We found the Polish Jewish community the most heterogeneous among all Jewish populations. The blood loci discriminate better than the protein loci. A number of possible interpretations and hypotheses for these and other results are offered. The method devised for this analysis should prove useful in studying similarities and differences for other groups of populations for which substantial biochemical polymorphic data are available.