The recombinant HLA‐B*5518 allele supports the evidence of conserved haplotype association of rare alleles

Abstract

Allelic polymorphism of the major histocompatibility complex arises mostly from gene recombination. Intralocus gene recombination usually involves short fragments of DNA leading most commonly to single-nucleotide substitutions and rarely involves large fragments. Here, we report a new recombinant human leukocyte antigen (HLA)-B*5518 allele that has arisen via recombination of a large fragment of DNA spanning more than 70 nucleotides. During routine HLA typing of potential volunteer donors for the National Marrow Donor Program((R)), a new HLA-B allele was identified in two donors from Guam. The allele, B*5518, appears to be a product of recombination between B*5502 and B*40. Exons 1, 3, and 4 of the new allele belong to B*5502, whereas part of exon 2 belongs to one of B*40 alleles. Introns 1 and 2 appear to belong to B*55, suggesting that the recombination event may have occurred within the homologous parts of exon 2.

Identification of a New HLA-B Allele (B*1576) by Haplotype Specific Extraction

“…Haplotype specific extraction provides a rapid, automated method for determining true (i.e. non-statistically derived) and previously unknown haplotypes, directly from genomic DNA, without requiring any familial information [4][5][6][7][8][9][10]. The method does not rely on amplification-based phasing methods which can be affected by polymorphic variation and eliminates the need for cloning or subcloning for the characterization of new alleles.…”

Identification of a novel HLA‐B*44 variant (B*4441) in three unrelated Caucasian individuals

“…Determination of human leukocyte antigen (HLA) class I and class II alleles at the high resolution level and the calculation of haplotype frequencies can provide valuable information for bone marrow donor search centres and the forensic medicine as well as advance the research in anthropology/HLA‐diversity and HLA‐associated diseases (2). Recent findings of unknown alleles in several individuals – as in the case of B*1565 (3), A*6824 (4) and B*5518 (5) – point at the possibility that there are still unknown sequence variants which are not perforce ‘rare’ ones. At least within defined areas and populations specific sequence variants seem to be represented in a greater number than expected.…”

HLA‐B*1586 is a novel, hybrid HLA‐B15/B22 allele with unique serology and haplotypic association

“…HLA‐B*15 is the most polymorphic of all HLA groups having over 100 members (1, 2). Numerous HLA‐B alleles are presumptive hybrids of more common alleles (3, 4). By nature, hybrid alleles present challenges to our classification schemes, and this is reflected in their intermediate serology.…”

“…Cw*0102 was reported as present from the Australian Red Cross Blood Service as well as our group. Identical apparent linkages from three separate groups suggest that HLA‐B*1586 has a conserved haplotype association as observed in other rare alleles (4).…”