Increased HLA class I and II diversity as 72 novel alleles are identified in volunteers for the National Marrow Donor Program Registry in 2010

Abstract

Seventy-two novel human leukocyte antigen (HLA) class I and class II alleles are described from volunteers for the 'Be The Match Registry®': 17 HLA-A alleles, 12 HLA-C alleles, 31 HLA-B alleles and 12 HLA-DRB1 alleles. Forty-six (≈ 64%) of the 72 novel alleles are single-nucleotide substitution variants when compared with their most homologous allele. Five of these single-nucleotide variants are silent substitutions and one creates a non-expressed allele (B*44:108N). The remaining novel alleles differ from their most similar allele by two to five nucleotide substitutions. One of the novel HLA-C alleles (C*07:150Q) is of questionable expression due to an insertion of 21 nucleotides starting at codon 143 that adds seven amino acids to exon 3. An inter-locus gene conversion may have created the novel allele HLA-A*23:31 that shares its codon differences with HLA-B*07:28. Some of the new alleles encode novel codons and unique amino acid changes at polymorphic positions in the HLA-A (codons 116 and 150), HLA-C (codon 114), HLA-B (codons 11, 21, 35, 42, 48, 73, 98 and 170) and HLA-DRB1 (codon 29) loci.

Resolving unknown nucleotides in the IPD-IMGT/HLA database by extended and full-length sequencing of HLA class I and II alleles

“…Since then, many HLA alleles have been determined to originating through recombination events, mostly intragenic (between alleles of the same locus) and rarely intergenic (between alleles of different loci). Among HLA-B alleles, B*53 and B*07 have previously been reported to be involved in recombination events; B*53:31 was identified as arisen by a gene conversion event between B*35:03:01 and B*44:02 or B*13:02 (Adamek et al 2015 ), B*07 has been reported as donor allele group for the alleles B*44:150 and B*08:79 (Balas et al 2012a , b ), but also for the allele A*23:31 that originated from an interlocus gene conversion (Lazaro et al 2012 ). Several B*07 alleles might also have been the result of a recombination event themselves, like B*07:12 , that seems to be a recombination between B*07:02 and either B*35 , 53 , or 58 , sharing intron 2 and first part of exon 3 sequences with the latter allele groups (Steiner et al 2001 ).…”

Characterization of 27 novel HLA class II alleles from China Marrow Donor Program

“…Numbering from the first codon of the mature protein . The altered codon(s) number and sequence of the most homologous alleles are compared with the novel allele that is listed second.…”

Description of five novel HLA‐B alleles, B*07:184, B*41:27, B*42:19, B*50:32 and B*57:63, identified in Brazilian individuals

“…The high level of HLA gene polymorphism has been extensively documented as the abundance of new alleles is steadily increasing (Lazaro et al ., , ; Robinson et al ., ) with the distribution varying greatly within human populations (Braun‐Prado et al ., ; Williams et al ., ; Maiers et al ., ; Gonzalez‐Galarza et al ., ). The HLA genetic diversity makes each individual genetically unique (Buhler et al ., ).…”