Abstract
HLA-B is the most polymorphic of the major histocompatibility complex classical class I loci. This polymorphism is mainly in exons 2 and 3, which code for the molecule’s α1 and α2 domains and include the antigenic peptide binding site. Recent studies have indicated that not only exons but also the intron 2 region may be involved in the generation of certain HLA-B alleles such as B * 3906 and B * 1522. To study the degree of intron 2 participation and the mechanisms that generate polymorphism at the HLA-B locus, intron 1 and 2 sequences from the HLA-B35, -B5, -B16 and -B15 groups of alleles were obtained. A group-specific intronic polymorphism was found: namely, B * 5301 shows intron 1 and 2 sequences identical to those found in all B35 alleles studied. On the other hand, B * 5101 and B * 52012 show the same intron 1 and 2 sequences and their intron 1 is the same as that found in the B35 group. This suggests that B5 and B35 groups of alleles may have arisen from a common ancestor. All known B16 alleles show the same introns 1 and 2, with the exception of B * 39061 and B * 39062, and all B15 alleles also bear the same introns 1 and 2, with the exception of B * 1522. Variability at intron 1 is more restricted than at intron 2, and the use of intron 1 for HLA-B allele phylogenetic analysis is better for grouping alleles of a postulated common origin. In conclusion, there is a remarkable conservation of intronic sequences within related HLA-B alleles, which probably reflects a common origin and perhaps a selective force avoiding DNA changes. Intronic sequences are also potentially useful to design DNA typing strategies.
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Received: 11 March 1997 / Revised: 29 May 1997
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Gómez-Casado, E., Vargas-Alarcón, G., Martinez-Laso, J. et al. Generation of the HLA-B35, -B5, -B16, and B15 groups of alleles studied by intron 1 and 2 sequence analysis. Immunogenetics 46, 469–476 (1997). https://doi.org/10.1007/s002510050307
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DOI: https://doi.org/10.1007/s002510050307