The noncoding regions of HLA-DRB uncover interlineage recombinations as a mechanism of HLA diversification

The mechanisms generating new alleles at the MHC loci are still unknown in detail, and several proposals have been made to explain the extent of polym orphism. The patchwork pattern of polymorphism in the 2nd exon of HLA-DRBI recommends this locus as a model for the study of the potential of interall elic gene conversion, In general, the inference of gene conversion-like eve nts based exclusively on exon sequence comparisons may be misleading becaus e the identity of the putative donor allele remains unknown. In this study, we describe five alleles of the HLA-DRBI gene, which intron regions give e vidence for interlineage recombination events either strictly located at th e 2nd exon or involving the adjacent Introns, Furthermore, we show that the noncoding regions provide important clues to the mechanisms of the generat ion of new alleles, and our results indicate that interlineage recombinatio ns may be hidden and are perhaps more frequent than currently expected.