International Journal of Molecular Veterinary Research, 2025, Vol.15, No.1, 43-50 http://animalscipublisher.com/index.php/ijmvr 45 antioxidant defense, apoptosis, and cytoskeleton rearrangement genes quickly and intensively. Major innate immune processes that are triggered include the Toll-like receptor signaling pathway, phagosome maturation, cytokine-cytokine receptor interactions, and lysosomal and complement cascades. Immune response genes in disease-resistant tilapia lines are upregulated and possess more active innate immune systems compared to disease-susceptible lines, which highlights the significance of these genes in resistance (Zhu et al., 2017; 2021; 2023). 3.2 Association between MHC gene diversity and disease resistance Although the papers presented here do not directly address tilapia major histocompatibility complex (MHC) gene diversity, in fish immunology it is established that MHC gene diversity is crucial for pathogen recognition and immune defense. Tilapia genetic studies have recorded heritability of resistance against bacterial and viral pathogens and that immune gene diversity, like MHC loci, most likely has a role. The finding of candidate genes within QTL regions associated with disease resistance, including immune signaling and antigen processing genes, suggests that MHC diversity may account for variation observed in resistance between and among strains and individuals (Barría et al., 2020). 3.3 Application of QTL and GWAS in tilapia disease resistance QTL mapping and GWAS are currently important methods applied to clarify the genetic mechanism of tilapia resistance to disease. For example, a significant QTL that imparts an extensive effect on resistance to Tilapia Lake Virus (TiLV) was identified in Nile tilapia in Oni22 chromosome, wherein candidate genes participating in viral response were indicated within the region. Similarly, GWAS for Streptococcus agalactiae resistance in hybrid red tilapia and GIFT strain identified numerous SNPs and QTLs explaining large fractions of the genetic difference for disease resistance. The outcomes support the application of marker-assisted and genomic selection to promote breeding of disease-resistant tilapia lines. Genomic selection approaches, such as BayesB and GBLUP, have been more accurate in disease-resistant trait prediction compared to the traditional pedigree-based approaches and have been regarded as promising strategies for sustainable aquaculture (Sukhavachana et al., 2020; Barría et al., 2021; Qiao et al., 2025). 4 Molecular Mechanisms of Disease Resistance in Tilapia 4.1 Key gene expression and signaling pathways in infection responses When infected by pathogens such as Streptococcus agalactiae, tilapia rapidly upregulate a broad array of immune-related genes. Transcriptomics and proteomics reveal that an enormous number of genes are differentially expressed in resistant versus susceptible fish, particularly at early post-infection time points. All these genes are involved in pathogen recognition, immune activation, antioxidant defense, apoptosis regulation, and cytoskeleton rearrangement. Key signaling pathways include the Toll-like receptor (TLR) pathway, cytokine-cytokine receptor interactions, phagosome maturation, lysosome activity, complement cascades, and MAPK and Jak-STAT pathways. Disease-resistant stocks of tilapia have enhanced and specific induction of immune response genes, such as TLR5, p38, CXCR3, and multiple interleukins, following pathogen challenge, that underpin their heightened resistance (Ken et al., 2017; Zhu et al., 2018; 2021; Zhang et al., 2024). 4.2 Roles of non-coding RNAs and epigenetic regulation in tilapia disease resistance Epigenetic mechanisms, specifically DNA methylation, are essential in immune response regulation in tilapia. Genomic methylation analysis reveals that resistant fish have elevated promoter methylation of immunity-related genes in regulating gene expression following infection. Differentially methylated regions (DMRs) and methylation-controlled genes Arnt2, Nhr38, and hoxa family genes are involved in resisting pathogens. Accessibility profiling of chromatin also shows that chromatin structure remodeling, particularly at the level of promoter regions, is associated with immune pathway activation like autophagy, Notch signaling, and endocytosis. Such epigenetic regulation like control of non-coding RNAs that modulate the immune response are the underlying mechanisms for differential disease resistance of tilapia strains (Hu et al., 2020; Qiao et al., 2024; Jiao et al., 2025).
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