New HLA alleles discovered by next generation sequencing in routine histocompatibility lab work in a medium-volume laboratory

Abstract

The immunogenetics research and clinical communities are undergoing a revolution in the way that Human Leukocyte Antigens (HLA) alleles are typed, thanks to the introduction and increasing acceptance of next-generation sequencing into laboratory practice. With the ability to sequence all exons of each allele, instead of the previously routine typing of exons 2 and 3 of class I and exon 2 of class II, the sequencing of previously unsequenced areas of HLA alleles is causing a host of new alleles to be discovered through the course of routine laboratory testing. In the first 4 months of routine next generation sequencing, we have identified 10 novel alleles that have been discovered through laboratory testing for all facets of HLA typing, i.e. solid organ transplantation, hematopoietic stem cell transplantation, disease association typing and pharmacogenomics testing. The advent of NGS HLA typing in routine clinical practice, and the concomitant routine typing of exons outside the norm, opens the window for rapid discovery of new HLA alleles and a potential for overwhelming the current HLA nomenclature naming conventions.