ABRAHAMS CHILDREN IN THE GENOME ERA: MAJOR JEWISH DIASPORA POPULATIONS COMPRISE DISTINCT GENETIC CLUSTERS WITH SHARED MIDDLE EASTERN ANCESTRY. L. Hao1,6, G. Atzmon2, C. Velez1, A. Pearlman1, B. Riley1, C. Campbell1, M. Sasson1, P. Palamara3, J. Shan4, D. Reynolds4, E. Friedman5, B. Morrow4, C. Oddoux1, I. Pe'er3, E. Burns2, H. Ostrer1 1) Department of Pediatrics, Human Genetics Program, NYU Langone Medical Center, New York, NY; 2) Department of Medicine, Albert Einstein College of Medicine, Bronx, NY; 3) Department of Computer Science, Columbia University, New York, NY; 4) Department of Genetics, Albert Einstein College of Medicine, Bronx, NY; 5) Chaim Sheba Medical Center, Tel Hashomer, Israel; 6) Center for Genome Informatics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ.

   Despite residence all over the world, Jewish populations have maintained continuous genetic, cultural, and religious tradition over 4,000 years. The unique ethnic makeup and social practices provide an invaluable opportunity to understand their genetic origins and migrations and to elucidate the genetic basis of complex disorders. To generate a comprehensive HapMap of ethnically diverse, healthy Jewish populations, we used the Affymetrix array 6.0 to genotype 381 samples recruited from 7 Jewish communities with different geographic origins: Eastern European Ashkenazim; Italian, Greek and Turkish Sephardim; Iranian, Iraqi, and Syrian Mizrahim (Middle Easterners). Here, we present population structure results from compiled datasets after merging with the Human Genome Diversity Project and the Population Reference Sample studies, which consisted of 146 non-Jewish Middle Easterners (Druze, Bedouin and Palestinian), 30 northern Africans (Mozabite from Algeria), 1547 Europeans, and 653 individuals from other African, Asian, Latin American, and Oceanian populations. Both principal component analyses and multi-dimensional scaling analysis of pairwise Fst distance show that Jewish populations form a cluster clearly distinct from all major continental populations. The results also reveal a finer population substructure in which each of 7 Jewish populations studied here form distinctive clusters - in each instance within group Fst was smaller than between group, although some groups (Iranian, Iraqi) demonstrated greater within group diversity and even sub-clusters, based on village of origin. By pairwise Fst analysis, the Jewish groups are closest to Southern Europeans (i.e. Tuscan Italians) and to Druze, Bedouins, Palestinians. Interestingly, the distance to the closest Southern European population follows the order from proximal to distal: Ashkenazi, Sephardic, Syrian, Iraqi, and Iranian, which reflects historical admixture with local communities. STRUCTURE results show that the Jewish Diaspora groups all demonstrated Middle Eastern ancestry, but varied significantly in the extent of European admixture. There is almost no European ancestry in Iranian and Iraqi Jews, whereas Syrian, Sephardic, and Ashkenazi Jews have European admixture ranging from 30%~60%. Analysis of identity-by-descent provides further insight on recent and distinct history of such populations. These results demonstrate the shared and distinctive genetic heritage of Jewish Diaspora groups.