HLA RNA Sequencing With Unique Molecular Identifiers Reveals High Allele-Specific Variability in mRNA Expression

Frontiers in Immunology

Dawit A. Yohannes¹  Tiira Johansson²  Päivi Saavalainen²  Jukka Partanen²  Satu Koskela² 

[1] Research Programs Unit, Translational Immunology Program, University of Helsinki, Helsinki, Finland;Research and Development, Finnish Red Cross Blood Service, Helsinki, Finland;

关键词: HLA;    allele-specific expression;    RNA sequencing;    unique molecular identifiers;    gene expression;   

DOI  :  10.3389/fimmu.2021.629059

来源: DOAJ

【 摘 要 】

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. Most studies have focused on the vast allelic variation in these genes; only a few studies have explored differences in the expression levels of HLA alleles. In this study, we quantified mRNA expression levels of HLA class I and II genes from peripheral blood samples of 50 healthy individuals. The gene- and allele-specific mRNA expression was assessed using unique molecular identifiers, which enabled PCR bias removal and calculation of the number of original mRNA transcripts. We identified differences in mRNA expression between different HLA genes and alleles. Our results suggest that HLA alleles are differentially expressed and these differences in expression levels are quantifiable using RNA sequencing technology. Our method provides novel insights into HLA research, and it can be applied to quantify 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.

【 授权许可】

Unknown