Biology subjects

Mukiibi, R.

Publications and source records attributed to Mukiibi, R..

3 recordsLinked to original sources

bioRxiv2026

MicroRNA modulation of viral nervous necrosis resistance in European seabass

MicroRNAs (miRNAs) are key post-transcriptional regulators of antiviral immunity, controlling gene expression by targeting 3 UTRs of immune-related transcripts. Despite their importance, the role of miRNAs in viral nervous necrosis (VNN) resistance in European seabass (Dicentrarchus labrax) is unexplored. Here, we characterized for the first time the brain miRNome of seabass from three VNN-resistance genotypes (susceptible, intermediate, resistant) across two genetically distinct seabass clusters. Differential expression analyses revealed cluster-specific patterns, with susceptible fish consistently showing overexpression of the differently expressed miRNAs (DEmiRNAs) as compared to the resistant fish. Considering the two genetic clusters in the study, miR-199-5p was differentially expressed between the VNN susceptible and resistant fish. This miRNA was found to be less expressed in the resistant individuals. Functional characterization of the miRNA predicted that it binds to two distinct miRNA recognition elements (MREs) within the ifi27l2a 3 UTR. These MREs flank a SNP (Chr3:10,082,380) previously associated with VNN survival. A strong negative correlation (r= -0.840) between miR-199-5p expression and ifi27l2a mRNA abundance further supports a post-transcriptional repression mechanism. Together, these results propose a regulatory model in which miR-199-5p modulates ifi27l2a expression, contributing to phenotypic variation in VNN resistance and positioning it as a promising biomarker for seabass aquaculture breeding.

genomics↗

bioRxiv2024

Integrated functional genomic analysis identifies the regulatory variants underlying a major QTL for disease resistance in European sea bass

BackgroundViral nervous necrosis (VNN) is a viral disease threatening the sustainability of global aquaculture, and affecting over 50 of farmed and ecologically important species. A major QTL for resistance to VNN has been previously described in European sea bass, but the underlying causal gene(s) and mutation(s) are unknown. To identify the mechanisms and genetic factors underpinning resistance to VNN, we integrated farmed and wild genetic data with multiple functional genomics assays in a farmed European sea bass population. ResultsA high heritability (h2 [~] 0.40) was estimated for VNN resistance. A major QTL for this trait was confirmed on chromosome 3, and whole-genome resequencing narrowed its location to a small region containing 4 copies of interferon alpha inducible protein 27-like 2A (IFI27L2A) genes, and one copy of the interferon alpha inducible protein 27-like 2 (IFI27L2) gene. RNA sequencing revealed a clear association between the QTL genotype and the expression of two of the IFI27L2A genes, and the IFI27L2 gene. Integration with chromatin accessibility and histone modification data pinpointed two SNPs in active regulatory regions of two of these genes (IFI27L2A and IFI27L2), and transcription factor binding site gains for the resistant alleles were predicted. These alleles, particularly the SNP variant CHR3:10077301, exhibited higher frequency in Eastern Mediterranean sea bass populations, which show considerably higher levels of resistance to VNN. ConclusionsThe SNP variant CHR3:10077301, through modulation of IFI27L2 and IFI27L2A genes, is likely the causative mutation underlying resistance to VNN in European sea bass. This is one of the first causative mutations discovered for disease resistance traits, and paves the way for marker-assisted selection as well as biotechnological approaches to enhance resistance to VNN in European sea bass and other susceptible species.

genetics↗

bioRxiv2021

The impact of Piscirickettsia Salmonis infection on genome-wide DNA methylation profile in Atlantic Salmon

Salmon rickettsial septicaemia (SRS), caused by the intracellular bacteria Piscirickettsia Salmonis, generates significant mortalities to farmed Atlantic salmon, particularly in Chile. Due to its economic importance, a wealth of research has focussed on the biological mechanisms underlying pathogenicity of P. salmonis, the host response, and genetic variation in host resistance. DNA methylation is a fundamental epigenetic mechanism that influences almost every biological process via the regulation of gene expression and plays a key role in the response of an organism to stimuli. In the current study, the role of head kidney and liver DNA methylation in the response to P. salmonis infection was investigated in a commercial Atlantic salmon population. A total of 66 salmon were profiled using reduced representation bisulphite sequencing (RRBS), with head kidney and liver methylomes compared between infected animals (3 and 9 days post infection) and uninfected controls. These included groups of salmon with divergent (high or low) breeding values for resistance to P. salmonis infection, to examine the influence of genetic resistance. Head kidney and liver showed organ-specific global methylation patterns, but with similar distribution of methylation across gene features. Integration of methylation with RNA-Seq data revealed that methylation levels predominantly showed a negative correlation with gene expression, although positive correlations were also observed. Methylation within the first exon showed the strongest negative correlation with gene expression. A total of 911 and 813 differentially methylated CpG sites were identified between infected and control samples in the head kidney at 3 and 9 days respectively, whereas only 30 and 44 sites were differentially methylated in the liver. Differential methylation in the head kidney was associated with immunological processes such as actin cytoskeleton regulation, phagocytosis, endocytosis and pathogen associated pattern receptor signaling. We also identified 113 and 48 differentially methylated sites between resistant and susceptible fish in the head kidney and liver respectively. Our results contribute to the growing understanding of the role of methylation in regulation of gene expression and response to infectious diseases, and in particular reveal key immunological functions regulated by methylation in Atlantic salmon in response to P. salmonis.

genomics↗