Global Gene Expression Patterns and Somatic Mutations in Sporadic Intracranial Aneurysms

Area of Science:

• Genomics
• Molecular Biology
• Pathology

Background:

• Intracranial aneurysms (IAs) are complex vascular diseases.
• Understanding the molecular mechanisms of IA pathogenesis is crucial for developing effective treatments.
• High-throughput sequencing offers powerful tools to investigate the genetic underpinnings of IAs.

Purpose of the Study:

• To identify the gene expression signature associated with intracranial aneurysms (IAs).
• To uncover the genetic factors contributing to IA development.
• To explore potential somatic alterations in key genes.

Main Methods:

• RNA sequencing was performed on 3 IA samples to determine gene expression levels.
• Bioinformatics analysis identified differentially expressed genes (DEGs) and their functions.
• Whole genome sequencing was conducted on 6 IA samples to detect somatic alterations.

Main Results:

• 1709 genes were found to be differentially expressed in IA tissues compared to normal arterial tissue.
• H19 and HIST1H3J were the most significantly up- and down-regulated genes, respectively.
• IKBKG, ACTB, and MKI67IP were identified as key hub proteins potentially involved in IA pathogenesis. Four candidate somatic single nucleotide variants, including MUC3B and BLM, were identified.

Conclusions:

• Transcriptome and whole genome sequencing data suggest no somatic mutations occurred in the identified DEGs.
• IKBKG, ACTB, and MKI67IP are highlighted as essential DEGs in IAs.
• MUC3B and BLM are identified as potentially important mutant genes in IA pathogenesis.