title: Further diversification of the HLA-B locus in Central American Amerindians: new B*39 and B*51 alleles in the Kuna of Panama.
abstract: Several new HLA-B locus alleles have been discovered in South American Amerindians. By contrast, analysis of the MHC class I alleles of North American native populations has revealed few new HLA-B alleles. This suggests that the HLA-B locus is evolving rapidly in South American populations. Here we describe the HLA-B locus alleles present in individuals from a Central American tribe, the Kuna of Panama. Using a sequence-based typing technique that separates alleles by denaturing gradient gel electrophoresis (DGGE) followed by direct sequencing, we determined the HLA-B alleles from eight Kunas. Two of the HLA-B alleles present in the Kuna have been previously described in other South American Amerindian populations; one allele has been characterized in a Mexican-American. We characterized two new HLA-B alleles in the Kuna, HLA-B*3911 and HLA-B*5110. HLA-B*3911 differed from HLA-B*3905 by only a single nucleotide substitution in exon 3. This substitution resulted in an amino acid replacement of leucine by arginine at residue 156 in the alpha 2 domain. Such a change may affect the repertoire of peptides that are bound by this molecule. HLA-B*5110 differed significantly from other HLA-B*51 alleles in that it is the result of an unusually large intra-locus recombination event of minimally 216 nucleotides. This recombination results in an allele that is part HLA-B*51 and part HLA-B*40. Thus, more dramatic recombination events may also play a role in the rapid evolution of the HLA-B locus in Amerindians.
authors.affiliation: Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Iwanaga
authors.forename: M
authors.initials: M
authors.lastname: Eberle
authors.forename: C J
authors.initials: CJ
authors.lastname: Kolman
authors.forename: E
authors.initials: E
authors.lastname: Bermingham
authors.forename: D I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D015235:HLA-B Antigens / Q000235:genetics*; D059946:HLA-B39 Antigen; D059949:HLA-B51 Antigen; D006801:Humans; D007197:Indians, Central American / Q000235:genetics*; D008969:Molecular Sequence Data; D010176:Panama
chemical_list: D015235:HLA-B Antigens; D059946:HLA-B39 Antigen; D059949:HLA-B51 Antigen