Human leucocyte antigens class II allele and haplotype association with Type 1 Diabetes in Madeira Island (Portugal).

This study confirms for Madeira Island (Portugal) population the Type 1 Diabetes (T1D) susceptible and protective Human leucocyte antigens (HLA) markers previously reported in other populations and adds some local specificities. Among the strongest T1D HLA associations, stands out, as susceptible, the alleles DRB1*04:05 (OR = 7.3), DQB1*03:02 (OR = 6.1) and DQA1*03:03 (OR = 4.5), as well as the haplotypes DRB1*04:05-DQA1*03:03-DQB1*03:02 (OR = 100.9) and DRB1*04:04-DQA1*03:01-DQB1*03:02 (OR = 22.1), and DQB1*06:02 (OR = 0.07) and DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.04) as protective. HLA-DQA1 positive for Arginine at position 52 (Arg52) (OR = 15.2) and HLA-DQB1 negative for Aspartic acid at the position 57 (Asp57) (OR = 9.0) alleles appear to be important genetic markers for T1D susceptibility, with higher odds ratio values than any single allele and than most of the haplotypes. Genotypes generated by the association of markers Arg52 DQA1 positive and Asp57 DQB1 negative increase T1D susceptibility much more than one would expected by a simple additive effect of those markers separately (OR = 26.9). This study also confirms an increased risk for DRB1*04/DRB1*03 heterozygote genotypes (OR = 16.8) and also a DRB1*04-DQA1*03:01-DQB1*03:02 haplotype susceptibility dependent on the DRB1*04 allele (DRB1*04:01, OR = 7.9; DRB1*04:02, OR = 3.2; DRB1*04:04, OR = 22.1).

HLA-DQA1 and HLA-DQB1 allele diversity and its extended haplotypes in Madeira Island (Portugal).

This study shows, for the first time, high-resolution allele frequencies of HLA-DQA1 loci in Madeira Island (Portugal) and allows us to better understand and refine present knowledge on DQB1 variation, with the identification of several alleles not previously reported in this population. Estimates on haplotype profile, involving HLA-A, HLA-B, HLA-DRB1, HLA-DQA1 and HLA-DQB1, are also reported.

HLA-A polymorphisms in four ethnic groups from Guinea-Bissau (West Africa) inferred from sequence-based typing.

Human leukocyte antigen (HLA)-A locus polymorphisms were examined at high-resolution level, using sequence-based typing, in the four most representative Guinea-Bissau (Northwest Africa) ethnic groups: Balanta, Bijagós, Fula and Papel. Despite the Fula group having significant differences when compared with the other three ethnic groups, all four groups most likely received a genetic input from non sub-Saharans. The Bijagós and Papel groups showed similarities to neighboring populations from Mali and Senegal. The Balanta, despite their oral tradition of an East Africa origin, show affinities to Cameroon populations, highly influenced by Bantu migrations. These results are congruent with historical sources and other genetic studies that support the finding that the Guinea-Bissau genetic pool was influenced by several migrations from North Africa, Sahara and East Africa.

HLA class I and II polymorphisms in Azores show different settlements in Oriental and Central islands.

Human leucocyte antigen-A, -B, -Cw, -DRB1, -DQA1 and -DQB1 polymorphisms were examined in the Azorean population. The data were obtained at high-resolution level, using polymerase chain reaction (PCR) with sequence-specific primer, PCR-sequence-specific oligonucleotides and sequence-based typing. The most frequent allele in each locus was: A*0201 (24.5%), B*510101 (9.8%), Cw*0401 (14.8%), DRB1*070101 (18.3%), DQA1*0201 (17.4%) and DQB1*0301 (19.4%). The predominant extended haplotype was A*0202-B*1503-Cw*0202-DRB1*090102-DQA1*0303- DQB1*0202 (1.9%), which was found to be absent in the Portuguese mainland. The present study corroborates historical sources that say the Azores were populated not only by Portuguese but also by other Europeans, mostly Flemish people. Despite dendrogram analysis showing some remote Asian genetic affinities, the lack of specific alleles and haplotypes from those populations does not allow us to conclude for direct influence. Haplotype and allele frequencies in Azores show no homogeneous distribution between Oriental and Central islands of this archipelago. The Oriental islands harbour several haplotypes already found in mainland Portugal and identified as Mediterranean and European. The Central group of islands on the contrary clearly shows an influence of north Europeans (most probably derived from a well-documented Flemish settlement), with much less affinity to mainland Portugal.

HLA genes in Portugal inferred from sequence-based typing: in the crossroad between Europe and Africa.

The human leukocyte antigen-A (HLA-A), -B and -DRB1 polymorphism was examined in the Portuguese population, discriminating between North, Centre and South inhabitants. All data were obtained at high-resolution level, using sequence-based typing. The most frequent allele at each locus was A* 020101 (26%), B* 440301 and B* 510101 (12% each) and DRB1* 070101 (15%). The predominant three-locus haplotype was A*020101-B*440301-DRB1*070101 (3.1%), highly frequent in North Portugal (5.4%), lower in Centre (2%) and absent in the South. The present study demonstrates that the Portuguese population has been genetically influenced by Europeans and North Africans, via several historic immigrations. North Portugal seems to concentrate, probably due to the pressure of Arab expansion, an ancient genetic pool originated from several North Africans and Europeans, influences throughout millenniums. South Portugal shows a North African genetic influence, probably of recent origin by means of Berbers accompanying Arab expansion. We found that Centre Portugal is the distribution limit of some alleles and haplotypes that characterize the North or the South of the country. Despite North, Centre and South Portugal not being significantly different in allele frequencies, this study shows that HLA allele and haplotype frequencies are not homogeneous in the country. North and South Portugal show more similarity to North Africans in opposition to Centre which appears closer to Europeans.

[HLA-B27 polymorphism and spondyloarthropathies]. / Polimorfismo do alelo HLA-B27 no desenvolvimento das espondilartropatias.

The association of HLA-B27 with ankylosing spondylitis (AS), and other spondyloarthropathies (SpA), remains as one of the strongest between HLA molecules and human disease. Since it was reported, in 1973, it has been extensively studied in order to understand the underlying pathogenic mechanism. The objective of this article is to review the current knowledge on the structure and polymorphism of HLA-B27 molecule, as well as describe the main pathogenic hypotheses trying to explain its association with AS.

Phylogeography of the Madeiran endemic lizard Lacerta dugesii inferred from mtDNA sequences.

Partial sequences from two mitochondrial DNA genes, cytochrome b and 12S rRNA, were used to assess the phylogenetic relationships of populations of Lacerta dugesii from the volcanic Atlantic islands of Madeira, the Desertas, Porto Santo, and the Selvagens. All four-island groups are genetically distinguishable and populations within each contain similar degrees of genetic diversity. Molecular clock estimates suggest that the islands were colonized much later after their emergence compared to other Atlantic islands, possibly due to their greater geographical isolation. Mismatch analysis of all populations is consistent with exponential growth, as expected after colonization of empty niches. The Selvagens contain genetic substructuring between the islets.

Distribution of HLA alleles in Portugal and Cabo Verde. Relationships with the slave trade route.

HLA-A, -B, and -DR frequencies were analysed in populations from Portugal and the Madeira and Cabo Verde Archipelagos, aiming to characterize their genetic composition. Portuguese settlers colonized both Archipelagos in the 15th and 16th centuries. Madeira received many sub-Saharan slaves to work in the sugar plantations, and Cabo Verde served as a pivotal market in the Atlantic slave trade and was populated by individuals coming from the Senegambia region of the West African coast. The population of Madeira shows the highest genetic diversity and the presence of alleles and haplotypes usually linked to sub-Saharan populations, the haplotypes accounting for 3.5% of the total. Cabo Verde presents typical markers acknowledged to be of European or Ibero-Mediterranean origin, thus revealing the admixture of European settlers with Sub-Saharan slaves. Altogether the number of European haplotypes reaches 15% of the total. The Portuguese population shows a perceivable and significant heterogeneity both in allele and haplotype frequencies, unveiling a differential input of peoples from different origins. A PCA of the populations studied, plus other relevant ones, clearly shows gene heterogeneity in mainland Portugal as well as the differences and relationships between these populations and Madeira and Cabo Verde.