This descriptive, hypothesis-generating study examined whether 15q13.3-deletion cortical organoids show developmental transcriptomic differences overlapping retinoic acid (RA)-related gene-expression programs. Signatures derived from early RA exposure and prolonged, 7-day all-trans RA (ATRA) treatment were evaluated in public cortical organoid data from three deletion and 17 control donors. Donors, rather than individual samples, were the units of inference; 16 controls and all three deletion donors had sufficient time points for slope testing. Early human, early mouse, and conserved early RA signatures were not significant. A broad ATRA-derived differentiation score showed a negative deletion-control slope difference (exact P = 0.0083; false-discovery rate = 0.0206), but a non-RA maturation score was also significant. The prolonged score correlated strongly with maturity. Sensitivity analyses adjusting for measured maturation and composition did not identify an RA-specific component; neither the targeted RA program nor the covariate-adjusted joint trajectory test was significant. External and single-cell analyses provided biological context, not independent validation. The findings suggest a developmental/maturation-associated trajectory difference overlapping a broad prolonged ATRA-associated program. The three-donor case group and heterogeneous source models limit stability and generalizability; the results do not establish altered RA signaling, vitamin A deficiency, or retinoid-treatment relevance.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and progressive joint damage. Although numerous molecular contributors have been reported, the integrated regulatory architecture linking coding and non-coding transcripts remains incompletely defined. This study aimed to construct a multilayer lncRNA-miRNA-mRNA-transcription factor (TF) network to prioritize candidate regulators associated with RA. Publicly available RNA-sequencing datasets from RA and control samples were retrieved from the NCBI Sequence Read Archive. Differential expression analysis was performed using DESeq2. High-confidence miRNA-mRNA interactions were obtained from miRDip, miRNA-lncRNA associations from miRNet, and TF annotations from AnimalTFDB. Functional enrichment analyses were conducted to identify overrepresented biological themes. Network topology and module structure were evaluated in Cytoscape using CytoHubba and MCODE. Integration of interaction datasets identified 179 mRNAs targeted by 93 miRNAs, of which 90 miRNAs were connected to 404 annotated lncRNAs. Twenty-five TFs were incorporated into the regulatory framework. Degree-based analysis highlighted QKI, hsa-miR-497-5p, and KCNQ1OT1 as the most connected nodes within their respective categories. Module detection revealed five densely interconnected sub-networks, indicating coordinated regulatory organization. Several prioritized elements have previously been implicated in immune or inflammatory regulation, supporting the biological relevance of the network. This integrative analysis delineates a comprehensive regulatory landscape of RA and provides a ranked set of candidate molecules for future experimental validation. Among these, CCDC6 was identified as a downregulated gene positioned within a highly connected module and linked to multiple hub miRNAs and lncRNAs, suggesting potential functional importance in RA pathobiology.
Indigenous sheep constitute vital reservoirs of adaptive genetic diversity, yet their genomic signatures of adaptation are poorly understood. The present study provides a comprehensive genomic characterization of the endangered Karnah sheep (Ovis aries) native to North Kashmir, India. A total of 41,812 high-confidence SNPs were used across 266 individuals representing nine geographically and functionally diverse breeds (i.e., Karnah, Garole, Deccani, Changthangi, Tibetan, Australian Merino, Rambouillet, Suffolk, and Texel). Population structure analyses revealed pronounced genetic stratification with PC1-PC3 explaining 13.81
Developmental genes lie in transposon-poor regions, but whether that deficit is a conserved property of the promoters themselves remains unmeasured. Transposable element frequency was compared at neurodevelopmental disorder (NDD) promoters (TSS ±2 kb) in seven primates and two outgroups, contrasting a curated NDD gene set (SFARI and ClinGen; n=1020 ) with brain-expressed housekeeping genes ( n=1679 ). Alu depletion was significant in every primate ( r = -0.147 to -0.384 ), including the mouse lemur at 70 Mya. Mouse B1 and B2, SINEs amplified independently of primate Alu, each showed the deficit; the AT-biased Can-SINEs of dog did not. LINE-1 depletion was weak against housekeeping promoters but comparable to or deeper than the SINEs against the genome baseline, and more lineage-variable. The signal survived permutation testing, CpG and GC stratification, and gene-density and recombination controls. It persisted for alignment-defined rather than annotation-defined promoter windows, and against each genome’s own baseline in seven of nine, marmoset and dog excepted; the squirrel monkey showed no such exception. Against human controls matched on constraint, brain expression and GC it narrowed but persisted ( r = -0.106 ); Alu density does not otherwise track constraint. Windows away from the start site separate two components: the surrounding 250 kb is itself Alu-poor, and a promoter-proximal deficit survives normalisation to it. Depleted promoters coincided with active cis-regulatory elements, preferentially fetal-brain ones. Low promoter SINE content is thus an old feature of NDD-associated loci; whether the elements were never inserted or inserted and later lost is unresolved.
Kartagener’s syndrome (KS) is a rare, typically autosomal recessive ciliopathy and a subtype of primary ciliary dyskinesia (PCD), characterized by situs inversus, bronchiectasis, and chronic sinusitis. KS accounts for approximately 50
