Bruno Takao Real Karia

Background: The comprehensive elucidation of genomic relevance for mental disorder was, until recently, constrained by the limitations of microarrays or short-read sequencing (SRS). Long-read sequencing (LRS) provides access to complex classes of genetic variation and genomic architecture that are largely obscured in SRS approaches, making it a powerful tool for uncovering missing heritability and mechanistic insights in mental disorders. Objective: We synthesize current evidence on the application of LRS technologies across genomic, transcriptomic, and methylomic studies of mental disorders. The systematic review was conducted in accordance with PRISMA guidelines. Results and discussion: The literature search yielded 2,166 articles, and 14 were included in the review after applying inclusion and exclusion criteria. From a genomic perspective, LRS consistently outperformed SRS, increasing structural variant (SV) and de novo mutation (DNM) detection, particularly resolving medium-sized SVs and large inversions in repetitive regions. Transcriptomic studies established LRS as essential for achieving full-length transcript resolution, uncovering substantial novel isoform diversity and widespread alternative splicing events in the human neocortex. Crucially, LRS demonstrated that psychiatric risk is often conferred by dysregulated alternative splicing leading to isoform-specific imbalances, rather than altered total gene expression. At the epigenomic level, LRS enabled the haplotype-specific mapping of Allele-Specific Methylation within genome-wide significant loci, linking genetic risk to epigenetic dysregulation. Overall, LRS represents a significant technological advancement, providing the high-resolution molecular detail necessary to begin characterizing the complex relationships between genetic variation, splicing dynamics, and epigenetic modifications, thereby helping to contextualize psychiatric risk associations for future translational research.

LINC00152 does not affect U87 cell proliferation rate. A) qRT-PCR showing knockdown of LINC00152 after treatment with two different siRNAs. B) Cell proliferation rate measured by MTT assay of U87 cells treated with two different siRNA against LINC00152. C) qRT-PCR showing overexpression of LINC00152 after LINC00152 full length overexpression. D) Cell proliferation rates of U87 cells with and without LINC00152 overexpression.

LINC00152 full length and deletion mutants. A) Predicted secondary structures of LINC00152 deletion mutants. M2 and M3 lack the protein bound stem-loop. M8 is highlighted by the boxed area (nucleotides 280-401). On the other hand, M4 through M8 contain the protein bound stem-loop (highlighted by the boxed area). B) Schematics of LINC00152 siRNA and primers relative to LINC00152 sequence.

Expression of genes involved in EMT are decreased by si LINC00152 rescued by LINC00152 m8 overexpression. A-G) qRT-PCR showing (A) LINC00152, (B) TPM2, (C) PTX3, (D) IGFBP4, (E) TGM2, (F) SPP1, (G) LUM expression after siGL2 and pcDNA3, or siLINC00152_II and pcDNA3, or siLINC00152_II and LINC00152 m8 transfections.

Gastric cancer is the subject of clinical and basic studies due to its high incidence and mortality rates worldwide. Due to the diagnosis occurring in advanced stages and the classic treatment methodologies such as gastrectomy and chemotherapy, they are extremely aggressive and limit the quality of life of these patients. CRISPR/Cas9 is a tool that allows gene editing and has been used to explore the functions of genes related to gastric cancer, in addition to being used in the treatment of this neoplasm, greatly increasing our understanding of cancer genomics. In this mini-review, we seek the current status of the CRISPR/Cas9 gene-editing technology in gastric cancer research and clinical research.