Novel HLA-DQB1, DQA1, DPA1 and DPB1 alleles identified in the Australian New South Wales tissue typing laboratory

Abstract

Introduction of NGS into clinical histocompatibility laboratories has greatly increased the frequency of novel HLA allele discovery. We identified 9 DQA1, 7 DQB1, 8 DPA1 and 2 DPB1 novel alleles over the last 2 years. 92% (24 of 26) differed from their closest allele by single nucleotide substitutions detected in coding regions and 84% (22 of 26) contained polymorphism outside of exon 2. Identification of novel alleles in non-coding intronic regions were restricted to splice sites. Two novel alleles arising from nucleotide substitution affecting splicing were identified and named with questionable expression status. Novel alleles with polymorphism detected only in non-coding regions (introns and UTRs) were not reported. 21 additional DQA1, DQB1 and DPA1 alleles detected in multiple individuals as novel at the time of testing, were also detected in other laboratories. The number of novel alleles detected further emphasises the role of NGS in novel allele discovery.

Keywords: HLA; NGS; Novel HLA Alleles.