Description of a new HLA-E (E*01031) allele and its frequency in the Spanish population.

An HLA-E polymorphism study by oligotyping and DNA sequencing was carried out in the Spanish population. As a result, a new HLA-E allele (E*01031) initially assigned by polymerase chain reaction oligotyping as E*0104 was found. This allele presents a synonymous change at codon 77 (AAT-->AAC; Asn) when compared with the E*01032 allele. This position is located in the alpha-helix (alpha 1-domain) and is involved in the peptide binding region of the hypothetical HLA-E molecule. Among 60 Spanish individuals, HLA-E*0101 presents the highest phenotype frequency, followed in decreasing order by E*01032, E*01031 (new allele), and E*0102. Also, new partial intron 1 and complete intron 2 sequences from E*0101, E*01031, and E*01032 are described; the sequences are identical among the three forms. However, the intron 2 sequence of the E*0102 allele bears a two-base deletion not found in apes.

High polymorphism of Mhc-E locus in non-human primates: alleles with identical exon 2 and 3 are found in two different species.

Thirteen Mhc-E new sequences were found in eight individuals belonging to the Cercopithecinae family, i.e.: Macaca mulatta, Macaca fascicularis and Cercopithecus aethiops when studying E locus polymorphism. No changes were found in the invariant residues which are required for the correct conformation of the peptide presenting region which are conserved in classical Mhc class I molecules from fish and reptiles to humans; however, polymorphism of Mhc-E alleles is not limited to the three typical hypervariable regions per domain as it is in classical class I alleles. The rate of synonymous and nonsynonymous substitutions in the DNA sequence corresponding to the antigen binding site, compared to the remainder of exons 2 and 3 shows that the peptide-binding site is under high evolutionary pressure for stability since only synonymous substitutions have been found to be accepted in apes. Also, a clear example of trans-species evolution of allelism is found: two identical exon 2 and exon 3 sequences there exist belonging to individuals from different species (Mamu-Mhc-E*0101 and Mafa-Mhc-E*04). In addition, two Macaca mulatta individuals show an Mhc-E locus duplication. Finally, phylogenetic tree analysis shows that Mhc class I molecules found in Saguinus oedipus (described as Mhc-G homologues) are closer to Mhc-E sequences.

Relatedness among Basques, Portuguese, Spaniards, and Algerians studied by HLA allelic frequencies and haplotypes.

HLA-A, -B, -DRB1, -DQA1, and DQB1 alleles were studied in Iberian and Algerian populations by serology and DNA sequence methodologies. The genetic and cultural relatedness among Basques, Spaniards, and paleo-North Africans (Berbers or Tamazights) was established. Portuguese people have also maintained a certain degree of cultural and ethnic-specific characteristics since ancient times. The results of the present HLA study in Portuguese populations show that they have features in common with Basques and Spaniards from Madrid: a high frequency of the HLA-haplotypes A29-B44-DR7 (ancient western Europeans), A2-B7-DR15 (ancient Europeans and paleo-North Africans), and A1-B8-DR3 (Europeans) are found as common characteristics. Portuguese and Basques do not show the Mediterranean A33-B14-DR1 haplotype, suggesting a lower admixture with Mediterraneans; Spaniards and Algerians do have this haplotype in a relatively high frequency, indicating a more extensive Mediterranean genetic influence. The paleo-North African haplotype A30-B18-DR3 present in Basques, Algerians, and Spaniards is not found in Portuguese either. The Portuguese have a characteristic unique among world populations: a high frequency of HLA-A25-B18-DR15 and A26-B38-DR13, which may reflect a still detectable founder effect coming from ancient Portuguese, i.e., oestrimnios and conios; Basques and Algerians also show specific haplotypes, A11-B27-DR1 and A2-B35-DR11, respectively, probably showing a relatively lower degree of admixture. A neighbor-joining dendrogram place Basques, Portuguese, Spaniards, and Algerians closer to each other and more separated from other populations. Genetic, cultural, geological, and linguistic evidence also supports the hypothesis that people coming from a fertile Saharan area emigrated towards the north (southern Europe, Mesopotamia, the Mediterranean Islands, and the North African coast) when the climate changed drastically to hotter and drier ca 10 000 years B.C.

Mhc-E polymorphism in Pongidae primates: the same allele is found in two different species.

Mhc-E intron 1, exon 2, intron 2, and exon 3 from pygmy chimpanzee (Pan paniscus), chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orangutan (Pongo pygmaeus) have been sequenced; six new Mhc-E alleles have been obtained but sequence changes are only placed either in introns or in synonymous exonic bases. One pygmy chimpanzee Mhc-E DNA sequence is identical to another sequence from chimpanzee; the fact that no variation is found also at the intronic level suggests that these two species of chimpanzee may have recently separated and/or that both of them might only represent subspecies. Mhc-E phylogenetic trees separate two evolutionary groups: Pongidae, including humans, and Cercopithecinae; this is also found by studying another non-classical class I gene, Mhc-G. The Mhc-E alleles' invariance at the protein level supports that strong selective forces are operating at the Mhc-E locus, as has also been found in both Cercopithecinae and humans. These allelic and evolutionary data suggest an altogether different functionality for HLA-E (and also HLA-G) compared with classical class I proteins: i.e., sending negative (tolerogenic) signals to NK and T cells.

Description of a novel HLA-B35 (B*3514) allele found in a Mexican family of Nahua Aztec descent.

A new allele, HLA-B*3514, has been found in a Mexican family from Nahua descent. Its exon 2 is identical to that of B*3501 allele, but exon 3 bears a 3-base difference at codons 152 and 156, which results in Val-->Glu and Leu-->Trp changes, respectively, in the corresponding HLA molecule at the peptide-binding site. These substitutions may have originated from a DNA stretch donation from an allele belonging to the B15 group, enabling HLA-B*3514 to cope with the presentation of a new set of antigenic peptides. The high frequency of serologic B35 in Amerindians, together with the variety of B35 alleles detected by DNA sequencing in these populations, suggest that a frequent B35 subtype was present in the founder population and that several B35 subtypes may have been recently generated, probably due to the abrupt arrival of new pathogens following European invasions.

HLA allele and haplotype frequencies in Algerians. Relatedness to Spaniards and Basques.

The powerful genetic polymorphism of the HLA system has been used to identify individuals and populations. Ethnic groups may be characterized by specific HLA allele frequencies and particular extended HLA haplotypes; also, genetic relationships among these groups may be deduced. In the present study, serology and DNA typing were used to detect HLA-A, -B, -C, -DR, and -DQ alleles in each individual and to calculate characteristic haplotypes in Algerians. These results were compared to those previously obtained in other populations, particularly northern Mediterraneans; genetic distances and their respective dendrograms place Basques and Spaniards closer to Algerians than to other Europeans. Also, characteristic Basque and/or Spanish haplotypes are found in Algerians; i.e., A30-B18-Cw5-DR3-DQ2 and A1-B57-Cw7-DR7-DQ2. This supports the evidence that the Algerian population, mainly its paleo-North African component (Berbers), has a common descent with Basques and Spaniards, probably reflecting a preneolithic relationship between Iberians and paleo-North Africans.