Abstract

Postmortem mRNA degradation is considered to be the major concern in gene expression research utilizing human postmortem tissues. A key factor in this process is the postmortem interval (PMI), which is defined as the interval between death and sample collection. However, global patterns of postmortem mRNA degradation at individual gene levels across diverse human tissues remain largely unknown. In this study, we performed a systematic analysis of alteration of gene expression associated with PMI in human tissues. From the Genotype-Tissue Expression (GTEx) database, we evaluated gene expression levels of 2,016 high-quality postmortem samples from 316 donors of European descent, with PMI ranging from 1 to 27 hours. We found that PMI-related mRNA degradation is tissue-specific, gene-specific, and even genotype-dependent, thus drawing a more comprehensive picture of PMI-associated gene expression across diverse human tissues. Additionally, we also identified 266 differentially variable (DV) genes, such as DEFB4B and IFNG, whose expression is significantly dispersed between short PMI (S-PMI) and long PMI (L-PMI) groups. In summary, our analyses provide a comprehensive profile of PMI-associated gene expression, which will help interpret gene expression patterns in the evaluation of postmortem tissues.

Highlights

  • Postmortem mRNA degradation is considered to be the major concern in gene expression research utilizing human postmortem tissues

  • We evaluated the interaction between genotype and postmortem interval (PMI) to access the influence of genetic background on postmortem mRNA degradation in whole blood, which showed that postmortem degradation occurs in a genotype-specific manner

  • The central nervous system (CNS), as well as the lung, showed no sensitivity to postmortem mRNA degradation, which is consistent with previous studies[6, 20, 21]

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Summary

Introduction

Postmortem mRNA degradation is considered to be the major concern in gene expression research utilizing human postmortem tissues. Research using postmortem tissues from autopsies has been fundamental for improving knowledge of many diseases, including neurological disorders in particular[4, 5] Use of such tissue invariably involves a time delay, as tissue samples cannot immediately be stored in conditions which prevent mRNA degradation. Previous studies have reported that RNA degradation is associated with PMI in many species[8,9,10], including human tissues[11,12,13]. RNA integrity number (RIN) is an electrophoretic-basic method for evaluating the 28S to 18S ribosomal RNA (rRNA) ratio[14], which reflects RNA integrity as a whole

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