Molecular Immunology xxx (2005) xxx–xxx Short communication HLA genes in Madeira Island (Portugal) inferred from sequence-based typing: Footprints from different origins H´ elder Sp´ ınola a , J´ acome Bruges-Armas b , Marian Gantes Mora c , Derek Middleton d , Ant ´ onio Brehm a,∗ a Human Genetics Laboratory, University of Madeira, Campus of Penteada, 9000-399 Funchal, Portugal b Hospital Santo Esp´ ırito de Angra do Hero´ ısmo, Terceira, Azores, Portugal c Hospital Universit´ ario de Can ´ arias, Tenerife, Can´ arias, Spain d Northern Ireland Histocompatibility and Immunogenetics Laboratory, City Hospital and University of Ulster, Belfast, UK Received 26 August 2005; accepted 1 October 2005 Abstract Human leukocyte antigen (HLA)-A, HLA-B, and HLA-DRB1 polymorphisms were examined in Madeira Island populations. The data was obtained at high-resolution level, using sequence-based typing (SBT). The most frequent alleles at each loci were: A*020101 (24.6%), B*5101 (9.7%), B*440201 (9.2%), and DRB1*070101 (15.7%). The predominant three-loci haplotypes in Madeira were A*020101–B*510101–DRB1*130101 (2.7%) and A*010101–B*0801–DRB1*030101 (2.4%), previously found in north and central Portugal. The present study corroborates historical sources and other genetic studies that say Madeira were populated not only by Europeans, mostly Portuguese, but also sub-Saharan Africans due to slave trade. Comparison with other populations shows that Madeira experienced a stronger African influence due to slave trade than Portugal mainland and even the Azores archipelago. Despite this African genetic input, haplotype and allele frequencies were predominantly from European origin, mostly common to mainland Portugal. © 2005 Elsevier Ltd. All rights reserved. Keywords: HLA polymorphism; Sequence-based typing (SBT); Madeira island 1. Introduction The human leukocyte antigen (HLA) is one of the most poly- morphic genetic systems in humans and consists of a closely linked set of genes. HLA genes are highly important for medi- cal purposes (namely transplantation, autoimmune diseases and allergies), anthropological and forensic fields (Gibert et al., 2003; Boehncke et al., 1998; Riley and Olerup, 1992). Madeira Island (Portugal), located in the North Atlantic Ocean, was uninhabited when the settlement process began by the Portuguese in the 15th century. Settlers were mainly Por- tuguese but, when the Cabo Verde Islands were discovered (1462) and begun to be an outpost for sub-Saharan African slave trade, Madeira was one of the destinies for these African peoples. Most sub-Saharan slaves brought to Madeira were from North- western African coast (Carreira, 1983; Russel-Wood, 1998) and ∗ Corresponding author. Tel.: +35 1291 705383; fax: +35 1291 705399. E-mail address: brehm@uma.pt (A. Brehm). later were also introduced from Angola. In the middle of 16th century, African slaves constituted already 10% of the Madeira’s population and eventually become completely integrated into the society. Some studies have been done in order to characterize the Madeirean population genetic profile (Fernandes et al., 2001; Brehm et al., 2003) but only one used HLA generic class I and class II typing (Sp´ ınola et al., 2002). These studies showed that, besides the greater influence of Caucasians in the Madeira settlement, sub-Saharans left an important genetic imprint on the population. With recent developments in DNA typing, HLA can be studied at a high-resolution level, for example by sequencing. This high-resolution throughput allows an additional amount of information with greater relevance to a more specific HLA characterization, important in population’s comparisons and dis- ease studies (Ayed et al., 2004). Previous HLA generic typing revealed that the Madeirean population has an admixture of Cau- casoid and to a lesser degree, sub-Saharan alleles and haplotype frequencies (Sp´ ınola et al., 2002). 0161-5890/$ – see front matter © 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.molimm.2005.10.001 MIMM-1882; No. of Pages 3