Two DRβ allelic series defined by exon II-specific synthetic oligonucleotide genomic hybridization: A method of HLA typing?

Abstract

Comparisons of exon II HLA-DRβ sequences have shown that nucleotide variations are principally clustered within the following three regions: V1 (amino acid 8-15), V2 (25-32), and V3 (70-77). V1, V2, and V3-derived 24-mers have been synthesized, the DRβ sequences coming from DR1, DR3, DRw6, DR4, DR5, and DRw53 haplotypes. Each oligonucleotide was hydribized to Pvu II-digested DNA samples from 13 HLA genotyped families; therefore, 52 haplotypes have been investigated. Six polymorphic Pvu II fragments were detected, constituting two allelic series probably corresponding to the β1 and β2 locus of the DR region. The first series (β1) comprises a minimum of nine alleles while the second series (β2), which is less polymorphic, comprises at least four alleles. Certain patterns correlate perfectly with certain DR specificities, whereas other patterns define new subdivisions as in DR3 and DRw6 haplotypes. Although it appears that some mismatches do not always prevent hybridization in the conditions used in this work, this method will provide in many instances a convenient tool for HLA-DR typing.