Generation of the HLA-B35, -B5, -B16, and B15 groups of alleles studied by intron 1 and 2 sequence analysis.
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 alpha 1 and alpha 2 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.
Gómez-Casado
E
E
Department of Immunology, Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
Vargas-Alarcón
G
G
Martinez-Laso
J
J
Perez-Blas
M
M
Granados
J
J
Layrisse
Z
Z
Montoya
F
F
Varela
P
P
Arnaiz-Villena
A
A
D000483:Alleles; D001483:Base Sequence; D004247:DNA; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
D015235:HLA-B Antigens; D004247:DNA