The HLA gene complex is the most important, single genetic factor in susceptibility to most diseases with autoimmune or autoinflammatory origin and in transplantation matching. The majority of the studies have focused on the huge allelic variation in these genes; only a few studies have explored differences in expression levels of HLA alleles. To study the expression levels of HLA alleles more systematically we utilised two different RNA sequencing methods. Illumina RNAseq has a high sequencing accuracy and depth but is limited by the short read length, whereas Oxford Nanopore’s technology can sequence long templates, but has a poor accuracy. We studied allelic mRNA levels of HLA class I and II alleles from peripheral blood samples of 50 healthy individuals. The results demonstrate large differences in mRNA expression levels between HLA alleles. The method can be applied to quantitate the expression differences of HLA alleles in various tissues and to evaluate the role of this type of variation in transplantation matching and susceptibility to autoimmune diseases.

HLA RNAseq reveals high allele-specific variability in mRNA expression