Sequencing-based typing identifies novel alleles due to single nucleotide polymorphisms in 'conserved' regions

The Royal Perth Hospital laboratory has been using sequencing-based typing for all HLA loci since 2002. In the period to October 2005, approximately 12,000 HLA A and HLA B, 5000 HLA C and DQB1, and 17,000 DRB1 requests have been processed. Twenty nine novel alleles have been identified in that time. These comprise 10 HLA-A (including one null allele), five HLA-B, six HLA-C, six DRB1 (including a null allele), and one DQB1 novel allele. (At the time of identifying the DRB1 null allele, there were no other reported examples.) In addition, we have seen one example of a blast-specific HLA-A null allele. One HLA-A allele (HLA-A*0264) and one HLA-B allele (HLA-B*400104) were subsequently identified in other laboratories and submitted to the international ImMunoGeneTics project (IMGT) database.