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

HLA RNA Sequencing With Unique Molecular Identifiers Reveals High Allele-Specific Variability in mRNA Expression.
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HLA RNA测序与独特的分子标识符揭示了高等位基因特异性变异的mRNA表达。

DOI:
10.3389/fimmu.2021.629059
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发表时间:
2021
影响因子:
7.3
通讯作者:
Saavalainen P
Saavalainen P
中科院分区:
医学2区
文献类型:
--
作者:
Johansson T;Yohannes DA;Koskela S;Partanen J;Saavalainen P

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HLA基因复合体是对大多数自身免疫性或自身炎症性疾病的易感性和移植配型中最重要的单一遗传因素。大多数研究都集中在这些基因中的巨大等位基因变异上;只有少数研究探讨了HLA等位基因表达水平的差异。在这项研究中,我们定量的HLA I类和II类基因的mRNA表达水平从50个健康个体的外周血样本。使用独特的分子标识符评估基因和等位基因特异性mRNA表达,这使得能够去除PCR偏倚并计算原始mRNA转录本的数量。我们确定了不同HLA基因和等位基因之间mRNA表达的差异。我们的研究结果表明,HLA等位基因的差异表达,这些差异的表达水平是定量使用RNA测序技术。我们的方法为HLA研究提供了新的见解,它可以应用于量化HLA等位基因在各种组织中的表达差异,并评估这种类型的变异在移植配型和自身免疫性疾病易感性中的作用。
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.
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