doi: 10.1111/j.1744-313X.2006.00577.x © 2006 The Authors Journal compilation © 2006 Blackwell Publishing Ltd, International Journal of Immunogenetics 33, 93–103 93 Blackwell Publishing Ltd HLA class II genetic diversity in southern Tunisia and the Mediterranean area B. Abdennaji Guenounou,*¶ B. Yacoubi Loueslati,†¶ S. Buhler,‡¶ S. Hmida,§ H. Ennafaa,† H. Khodjet-Elkhil,† N. Moojat,§ A. Dridi,§ K. Boukef,§ A. Ben Ammar Elgaaied† & A. Sanchez-Mazas‡ Summary North Africa is populated by many Arab- and Berber- speaking populations whose genetic history is still poorly understood. In this study, we analyse the HLA-DRB1 and DQB1 molecular diversity in three populations from the south of Tunisia — Berbers from Jerba, Berbers from Matmata and Arabs from Gabes — and we compare them to a large set of populations from the whole Mediterranean region. Among the three populations studied, the Berbers from Jerba are the most peculiar, as they diverge signifi- cantly from other North Africans while being genetically highly diversified and close to populations from the Near East. Thus, Jerba may have been a crossing point, in historical times, where colonization from the eastern Mediterranean area left significant genetic traces. By contrast, the populations from Matmata and Gabes are genetically similar to other Arab and Berber-speaking populations from different areas of the Maghrib, despite some peculiar allele and haplotype frequencies. At a larger scale, northwest Africa and southwest Europe are closely related according to these polymorphisms, while the populations from the eastern Mediterranean area are much more differentiated. The close genetic relatedness found for HLA among populations of the western Medi- terranean region challenges previous results based on Y chromosome analyses, where the Gibraltar Strait appeared to constitute a main genetic barrier. Introduction The major histocompatibility complex in humans, or HLA, is a highly variable genetic system constituted by six main polymorphic loci — A, B, C, DRB1, DQB1 and DPB1 — located on the short arm of chromosome 6. Besides its crucial role in human clinical transplantation, the HLA system is also very informative in anthropological studies, where it is used to describe population genetic relation- ships in relation to past migration events. During the last decade, DNA typing techniques have been developed to identify HLA alleles with a high-resolution power, and more than 2000 different alleles are currently identified at the six main loci (121 at DPB1, 69 at DQB1, 511 at DRB, 748 at B, 217 at C and 429 at A, according to a recent record 1 ). Among the different HLA loci, DRB1 and DQB1 have been tested by molecular typing since the 11th interna- tional histocompatibility workshop (held in Yokohama in 1991). Since then, a very large set of populations have been studied worldwide for these loci (Imanishi et al., 1992; Clayton et al., 1997; Mack et al., in press; Sanchez- Mazas, in press; Single et al., in press-b), through genetic comparisons at different geographical levels. In addition, as HLA-DRB1 and DQB1 alleles are associated to each other by a significant level of linkage disequilibrium, two- locus haplotype frequencies are also relevant to analyse population relationships (Imanishi et al., 1992; Bodmer, 1987; Single et al., in press-a). Several studies have been devoted to the analysis of HLA-DRB1 and DQB1 in North African populations, namely Moroccan and Algerian Berbers and Arabs (Djoulah et al., 1994; Arnaiz-Villena et al., 1995; Izaabel et al., 1996), Egyptians (Hafez & El Chennawi, 1986; El Chenawi et al., 1996) and Tunisians (Ayed et al., 1987; Jenhani et al., 1989; Hmida et al., 1995). However, no Berber population was ever investigated in Tunisia despite the presence of many Berber communities. We thus undertook field studies in two distinct areas of that * Regional Center of Blood Transfusion, Gabes, Tunisia, † Laboratory of Molecular Genetics, Immunology and Biotechnology, University of Sciences of Tunis, Tunis, Tunisia ‡ Laboratory of Anthropology, Genetics and Peopling history (AGP), Department of Anthropology and Ecology, University of Geneva, Geneva, Switzerland, § Center of Blood Transfusion, Tunis, Tunisia ¶ These authors contributed equally to the work. Received 19 January 2005; revised 18 November 2005; accepted 21 November 2005 Correspondence: Alicia Sanchez-Mazas, Laboratory of Anthropology, Genetics and Peopling history (AGP), Department of Anthropology and Ecology, University of Geneva, 12 rue Gustave-Revilliod, CH-1227 Geneva, Switzerland. Tel: +4122-379.6984; Fax: +4122-379.3194; E-mail: alicia.sanchez-mazas@anthro.unige.ch 1 http://www.anthonynolan.com/HIG/lists on 9 February 2006.