A Systems Biology Approach on the Regulatory Footprint of Human Endogenous Retroviruses (HERVs)

Μαρκόπουλος, Γεώργιος

doi:10.3390/diseases10040098

Cited by 2 publications

(1 citation statement)

References 130 publications

(137 reference statements)

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“…Genomic annotation and analysis were performed, following previously established systems biology approaches [33][34][35]. Gene-specific analysis was performed with the Genomic Regions Enrichment of Annotations Tool (GREAT) (great.stanford.edu, accessed on 2 September 2023) [36].…”

Section: Genomic Annotation and Analysis Of Genomic Distributionmentioning

confidence: 99%

Cancer Associated PRDM9: Implications for Linking Genomic Instability and Meiotic Recombination

Ladias,

Markopoulos,

Kostoulas

et al. 2023

IJMS

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The PR domain-containing 9 or PRDM9 is a gene recognized for its fundamental role in meiosis, a process essential for forming reproductive cells. Recent findings have implicated alterations in the PRDM9, particularly its zinc finger motifs, in the onset and progression of cancer. This association is manifested through genomic instability and the misregulation of genes critical to cell growth, proliferation, and differentiation. In our comprehensive study, we harnessed advanced bioinformatic mining tools to delve deep into the intricate relationship between PRDM9F and cancer. We analyzed 136,752 breakpoints and found an undeniable association between specific PRDM9 motifs and the occurrence of double-strand breaks, a phenomenon evidenced in every cancer profile examined. Utilizing R statistical querying and the Regioner package, 55 unique sequence variations of PRDM9 were statistically correlated with cancer, from a pool of 1024 variations. A robust analysis using the Enrichr tool revealed prominent associations with various cancer types. Moreover, connections were noted with specific phenotypic conditions and molecular functions, underlining the pervasive influence of PRDM9 variations in the biological spectrum. The Reactome tool identified 25 significant pathways associated with cancer, offering insights into the mechanistic underpinnings linking PRDM9 to cancer progression. This detailed analysis not only confirms the pivotal role of PRDM9 in cancer development, but also unveils a complex network of biological processes influenced by its variations. The insights gained lay a solid foundation for future research aimed at deciphering the mechanistic pathways of PRDM9, offering prospects for targeted interventions and innovative therapeutic approaches in cancer management.

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Section: Genomic Annotation and Analysis Of Genomic Distributionmentioning

confidence: 99%

Cancer Associated PRDM9: Implications for Linking Genomic Instability and Meiotic Recombination

Ladias,

Markopoulos,

Kostoulas

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

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Sequence Motif Analysis of PRDM9 and Short Inverted Repeats Suggests Their Contribution to Human Microdeletion and Microduplication Syndromes

et al. 2023

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Holliday junctions are the first recognized templates of legitimate recombination. Their prime physiological role is meiotic homologous recombination, resulting in rearrangements of the genetic material. In humans, recombination hotspots follow a distinct epigenetic pattern designated by the presence of PR domain-containing protein 9 (PRDM9). Repetitive DNA elements can replicate in the genome and can pair with short inverted repeats (SIRs) that form Holliday junctions in a significantly high frequency in vitro. Remarkably, PRDM9 and SIR sequence motifs, which may have the potential to act as recombination primers associated with transposable elements (TEs) and their presence, may lead to gradual spreading of recombination events in human genomes. Microdeletion and microduplication syndromes (MMSs) constitute a significant entity of genetic abnormalities, almost equal in frequency to aneuploidies. Based on our custom database, which includes all MMSs shorter than 5 Mbs in length which is the cut-off point for the standard cytogenetic resolution, we found that the majority of MMSs were present in sequences shorter than 0.5 Mbs. A high probability of TE-associated and non-TE-associated PRDM9/SIR sequence motifs was found in short and long MMSs. Significantly, following the Reactome pathway analysis, a number of affected genes have been associated with the pathophysiological pathways linked to MMSs. In conclusion, PRDM9 or SIR sequence motifs in regions spanning MMSs hotspots underlie a potential functional mechanism for MMS occurrences during recombination.

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A Systems Biology Approach on the Regulatory Footprint of Human Endogenous Retroviruses (HERVs)

Cited by 2 publications

References 130 publications

Cancer Associated PRDM9: Implications for Linking Genomic Instability and Meiotic Recombination

Cancer Associated PRDM9: Implications for Linking Genomic Instability and Meiotic Recombination

Sequence Motif Analysis of PRDM9 and Short Inverted Repeats Suggests Their Contribution to Human Microdeletion and Microduplication Syndromes

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