Pseudogenes as Functionally Significant Elements of the Genome

Kovalenko, T. F.; Patrushev, Lev I.

doi:10.1134/s0006297918110044

Cited by 51 publications

(51 citation statements)

References 129 publications

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“…Interestingly, we found that most genes of the top 30 MDG differentially 5hmC markers were pseudogenes. The experimental data obtained during recent years indicate this understanding of the nature of pseudogenes is not entirely correct, and many pseudogenes are functionally significant elements of the genome and may play a regulatory role in the form of non-coding RNA [57][58][59]. Thus, we speculated that 5hmC regulated gene expression by regulating the production of pseudogene RNA.…”

Section: Discussionmentioning

confidence: 97%

5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic and predictive biomarkers for coronary artery disease

et al. 2020

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Background: The 5-hydroxymethylcytosine (5hmC) DNA modification is an epigenetic marker involved in a range of biological processes. Its function has been studied extensively in tumors, neurodegenerative diseases, and atherosclerosis. Studies have reported that 5hmC modification is closely related to the phenotype transformation of vascular smooth muscle cells and endothelial dysfunction. However, its role in coronary artery disease (CAD) has not been fully studied. Results: To investigate whether 5hmC modification correlates with CAD pathogenesis and whether 5hmC can be used as a biomarker, we used a low-input whole-genome sequencing technology based on selective chemical capture (hmC-Seal) to firstly generate the 5hmC profiles in the circulating cell-free DNA(cfDNA) of CAD patients, including stable coronary artery disease (sCAD) patients and acute myocardial infarction (AMI) patients. We detected a significant difference of 5hmC enrichment in gene bodies from CAD patients compared with normal coronary artery (NCA) individuals. Our results showed that CAD patients can be well separated from NCA individuals by 5hmC markers. The prediction performance of the model established by differentially regulated 5hmc modified genes were superior to common clinical indicators for the diagnosis of CAD (AUC = 0.93) and sCAD (AUC = 0.93). Specially, we found that 5hmC markers in cfDNA showed prediction potential for AMI (AUC = 0.95), which was superior to that of cardiac troponin I, muscle/brain creatine kinase, and myoglobin. Conclusions: Our results suggest that 5hmC markers derived from cfDNA can serve as effective epigenetic biomarkers for minimally noninvasive diagnosis and prediction of CAD.

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Section: Discussionmentioning

confidence: 97%

5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic and predictive biomarkers for coronary artery disease

et al. 2020

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“…On the contrary, a low expression is detected in adrenal gland, colon and pituitary gland (https://amp.pharm.mssm.edu/Harmonizome/gene/ EEF1DP3). It is known that lncRNAs, as pseudogenes as well as the others ncRNAs, may modulate the gene expression both at the transcriptional level, interacting with the promotor of parental gene o other genes, and posttranscriptional level, acting as microRNA decoys and so they may play key roles in cellular biological processes (Chan and Tay, 2018;Hu et al, 2018;Kovalenko and Patrushev, 2018). Nowadays, is still unknown the exact role of EEF1DP3 in healthy tissues.…”

Section: Transcriptionmentioning

confidence: 99%

EEF1DP3 (Eukaryotic translation elongation factor 1 delta pseudogene 3)

Cristiano¹

2020

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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“…Pseudogenes are DNA sequences with high homology to functional genes. More than 17,000 pseudogenes have been identified in the human genome and up to 10% of them are transcribed (Kovalenko and Patrushev, 2018). Even if pseudogenes are considered as ancient genes that have lost their functions (Portin, 2002), they still participate to the regulation of their parental gene expression at both transcriptional and translational levels (Kovalenko and Patrushev, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…More than 17,000 pseudogenes have been identified in the human genome and up to 10% of them are transcribed (Kovalenko and Patrushev, 2018). Even if pseudogenes are considered as ancient genes that have lost their functions (Portin, 2002), they still participate to the regulation of their parental gene expression at both transcriptional and translational levels (Kovalenko and Patrushev, 2018). Pseudogenes can act as competing endogenous RNA (ceRNA) toward their parental gene and compete for regulatory microRNA (miRNA) (Costa et al, 2012;Kovalenko and Patrushev, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Even if pseudogenes are considered as ancient genes that have lost their functions (Portin, 2002), they still participate to the regulation of their parental gene expression at both transcriptional and translational levels (Kovalenko and Patrushev, 2018). Pseudogenes can act as competing endogenous RNA (ceRNA) toward their parental gene and compete for regulatory microRNA (miRNA) (Costa et al, 2012;Kovalenko and Patrushev, 2018). By these mechanisms, the ratio between the amount of gene and pseudogene transcripts modulates the expression of the gene.…”

Section: Introductionmentioning

confidence: 99%

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Quality Control Strategy for CRISPR-Cas9-Based Gene Editing Complicated by a Pseudogene

et al. 2020

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CRISPR-Cas9 mediated gene editing in induced pluripotent stem cells became an efficient tool to investigate biological mechanisms underlying genetic-driven diseases while accounting for the respective genetic background. This technique relies on the targeting of a specific nucleotide sequence present in the gene of interest. Therefore, the gene editing of some genes can be complicated by non-coding pseudogenes presenting a high homology of sequence with their respective genes. Among them, GBA is raising special interest because of its implication as the most common genetic risk factor for Parkinson's disease. In this study, we present an easy-to-use CRISPR-Cas9 gene editing strategy allowing for specific editing of point mutations in a gene without genetic alteration of its pseudogene exemplified by the correction or insertion of the common N370S mutation in GBA. A quality control strategy by combined fluorescence and PCR-based screening allows the early identification of correctly edited clones with unambiguous identification of the status of its pseudogene, GBAP1. Successful gene editing was confirmed by functional validation. Our work presents the first CRISPR-Cas9 based editing of a point mutation in GBA and paves the way for technically demanding gene engineering due to the presence of pseudogenes.

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Pseudogenes as Functionally Significant Elements of the Genome

Cited by 51 publications

References 129 publications

5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic and predictive biomarkers for coronary artery disease

5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic and predictive biomarkers for coronary artery disease

EEF1DP3 (Eukaryotic translation elongation factor 1 delta pseudogene 3)

Quality Control Strategy for CRISPR-Cas9-Based Gene Editing Complicated by a Pseudogene

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