High-resolution HLA ABDRB1 haplotype frequencies from the Ezer Mizion Bone Marrow Donor Registry in Israel Sigal Manor a,⇑,1 , Michael Halagan b,1 , Nira Shriki a , Isaac Yaniv a,c,d , Bracha Zisser a , Martin Maiers b , Abeer Madbouly b , Jerry Stein c,d a Ezer Mizion Bone Marrow Donor Registry, Petach Tikva, Israel b Bioinformatics Research, National Marrow Donor Program, Minneapolis, MN, USA c Bone Marrow Transplant Unit, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel d Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel article info Article history: Received 10 August 2016 Revised 15 September 2016 Accepted 16 September 2016 Available online xxxx Keywords: HLA Haplotype and allele frequencies Jewish population Bone marrow donor registry abstract We have investigated HLA population alleles and haplotype frequencies for the ethnicities that comprise the contemporary population of Israel, using a large data set from the Ezer Mizion Bone Barrow Donor Registry. We genotyped 275,699 individuals at the HLA-A, -B and -DRB1 loci using HLA genotyping methods. HLA ABDRB1 haplotype frequencies were estimated from 19 sub-ethnic Jewish populations and other non-Jewish minorities using the maximum likelihood model, which accommodates typing ambiguities. We present overall and sub-ethnicity specific HLA diversity results of the registry, which will help guide a data-driven strategy for future registry expansion. Ó 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction Israel is home to the entire genetic spectrum of the Jewish Dias- pora as well as for non-Jewish minorities, leading to marked ethnic diversity in a country of only eight million individuals. Before the founding of the modern state of Israel (1948), the Jewish Diaspora consisted of separate Jewish communities in Europe, North Africa, and Asia. Ancient communities of Jewish exiles formed in Iran and Iraq from the 7th to the 5th centuries BCE. From the 1st century BCE onward, Jewish communities spread westward through the north and south coasts of the Mediterranean basin, throughout the Levant and inland into the European continent. Subsequently, Jewish populations expanded in central and eastern Europe, along the North African coast and in the southern Arabian peninsula. Jews migrated eastwards from the Persian empire and reached as far as India and China. Toward the late 19th century through the 20th century, there was significant immigration of Jews from Eur- ope to North and South America. Admixtures of Jewish migrants with indigenous host populations led to increasing genetic diver- sity between individual Diaspora communities, while cultural and religious forces maintained coherence of the Jewish people [1–3]. During the last 100 years, increasing immigration to Israel, together with the growth of Muslim and Druze populations within the boundaries of the State have resulted in a panoply of sub- ethnicities that make up the patchwork of modern Israeli society. As second and third generation Israelis start marrying outside of their ancestral subethnicities, an additional layer of allelic diversity has been introduced into the HLA landscape in Israel, leading to intergenerational immunogenetic differences within the Israeli population [4]. In the last decades, the successful use of highly matched unrelated volunteer donors for hematopoietic stem cell transplan- tation (HSCT) has stimulated the development of many national volunteer unrelated donor stem cell registries. This paper outlines analyses of HLA population haplotype frequencies in a large stem cell donor registry to characterize the genetic population profile of the contemporary Israeli population. In addition to the large extent of the population size analyzed, the high-resolution HLA profile presented in this study improves on data obtained in previ- ous studies [2,5–8]. This analysis is the first phase of a project that seeks to guide strategic planning for donor recruitment and expan- sion of the Ezer Mizion Bone Marrow Donor Registry (EM BMDR) in Israel. http://dx.doi.org/10.1016/j.humimm.2016.09.004 0198-8859/Ó 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. ⇑ Corresponding author at: Ezer Mizion Bone Marrow Donor Registry, 40 Kaplan St., Petach Tikva 49210, Israel. E-mail address: sigal@bmdr.org.il (S. Manor). 1 These authors contributed equally to this work. Human Immunology xxx (2016) xxx–xxx Contents lists available at ScienceDirect www.ashi-hla.org journal homepage: www.elsevier.com/locate/humimm Please cite this article in press as: S. Manor et al., High-resolution HLA ABDRB1 haplotype frequencies from the Ezer Mizion Bone Marrow Donor Reg- istry in Israel, Hum. Immunol. (2016), http://dx.doi.org/10.1016/j.humimm.2016.09.004 Downloaded from ClinicalKey.com at CONSORTIUM MEDICAL LIBRARIES - ISRAEL -Rabin Medical Center (Beilinson October 09, 2016. For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved.