Yuju Lee1†, Dain Lee2†, Julan Kim2, Tae-Hee Kim1, Chaehyeon Lim2, Hyejin Kim2, Jong-Won Park2, Yoonji Chung3, Yeongkuk Kim4, Min Sung Kim5, Seung Hwan Lee3, Woo-jai Lee5, Hyun-Chul Kim2*, Hee-Bok Park1
1Department of Animal Resources Science, Kongju National University, Yesan, 32439, Korea
2Genetics and Breeding Research Center, National Institute of Fisheries Science, Geoje 53334, Korea
3Division of Animal and Dairy Science, Chungnam National University, Deajeon 34134, Korea
4Quantomic, Deajeon 34167, Korea
5BLUGEN, Busan 48071, Korea
Correspondence to Hee-Bok Park, E-mail: heebokpark@kongju.ac.kr
†These authors contributed equally to this work.
Volume 8, Number 4, Pages 107-116, December 2024.
Journal of Animal Breeding and Genomics 2024, 8(4), 107-116. https://doi.org/10.12972/jabng.20240401
Received on 28 October, 2024, Revised on 09 December, 2024, Accepted on 09 December, 2024, Published on 31 December, 2024.
Copyright © 2024 Korean Society of Animal Breeding and Genetics.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0).
The olive flounder (Paralichthys olivaceus) is one of the most economically important fish species in South Korea’s aquaculture industry. However, Edwardsiellosis, caused by Edwardsiella tarda (E. tarda), poses a significant threat to this industry, resulting in high mortality rates and economic losses. The aim of this study is to identify genetic loci associated with Edwardsiellosis resistance in olive flounder using a genome-wide association study (GWAS). A challenge experiment was conducted, infecting 2,939 flounders with E. tarda and recording survival traits. Genotyping was performed using a 60K SNP array, followed by statistical genetic analysis using SPACox software, which identified four significant SNPs on chromosomes 10, 13, 18, and 21. These SNPs were located in or near positional candidate genes for inflammation and immune responses, such as STXBP5L, MEF2D, and HOMER1, indicating their potential involvement in bacterial defense mechanisms. Biological pathway analysis revealed several significant pathways, including Apelin signaling, ECM-receptor interaction, Calcium signaling, and PI3K-Akt signaling, which are known to regulate immune cell activity and inflammation. These findings provide important insights into the genetic mechanisms of disease resistance in olive f lounder and offer valuable resources for future selective breeding programs aimed at enhancing Edwardsiellosis resistance.
Disease, Edwardsiellosis, Genome-wide association study, Olive flounder, SNP
이 논문은 국립수산과학원(수산과학연구사업 R2024032)의 지원으로 수행되었습니다.
Arranz A., Doxaki C., Vergadi E., Martinez de la Torre Y., Vaporidi K., Lagoudaki E. D., Ieronymaki E., Androulidaki A., Venihaki M. and Margioris A. N. 2012. Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization. Proceedings of the National Academy of Sciences. 109(24):9517-9522.
[DOI][PubMed][PMC]
Bi W., Fritsche L. G., Mukherjee B., Kim S. and Lee S. 2020. A Fast and Accurate Method for Genome-Wide Time-to-Event Data Analysis and Its Application to UK Biobank. The American Journal of Human Genetics. 107(2):222-233.
[DOI][PubMed][PMC]
Chang C. C., Chow C. C., Tellier L. C., Vattikuti S., Purcell S. M. and Lee J. J. 2015. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience. 4(1):s13742-8.
[DOI][PubMed][PMC]
Chen Y., Chen Y., Shi C., Huang Z., Zhang Y., Li S., Li Y., Ye J., Yu C. and Li Z. 2018. SOAPnuke: a MapReduce acceleration-supported software for integrated quality control and preprocessing of high-throughput sequencing data. Gigascience. 7(1):gix120.
[DOI]
Connolly S. F. and Kusner D. J. 2007. The regulation of dendritic cell function by calcium-signaling and its inhibition by microbial pathogens. Immunol.Res. 39:115-127.
[DOI][PubMed]
Danecek P., Auton A., Abecasis G., Albers C. A., Banks E., DePristo M. A., Handsaker R. E., Lunter G., Marth G. T. and Sherry S. T. 2011. The variant call format and VCFtools. Bioinformatics. 27(15):2156-2158.
[DOI][PubMed][PMC]
Ewing W. H., McWhorter A. C., Escobar M. R. and Lubin A. H. 1965. Edwardsiella, a new genus of Enterobacteriaceae based on a new species, E. tarda. Int.J.Syst.Evol.Microbiol. 15(1):33-38.
[DOI]
Fei X., Dou Y., Wang L., Wu X., Huan Y., Wu S., He X., Lv W., Wei J. and Fei Z. 2022. Homer1 promotes the conversion of A1 astrocytes to A2 astrocytes and improves the recovery of transgenic mice after intracerebral hemorrhage. Journal of Neuroinflammation. 19(1):67.
[DOI][PubMed][PMC]
Guillermet-Guibert J., Bjorklof K., Salpekar A., Gonella C., Ramadani F., Bilancio A., Meek S., Smith A. J., Okkenhaug K. and Vanhaesebroeck B. 2008. The p110β isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110γ. Proceedings of the National Academy of Sciences. 105(24):8292-8297.
[DOI][PubMed][PMC]
Harjunpää H., Llort Asens M., Guenther C. and Fagerholm S. C. 2019. Cell adhesion molecules and their roles and regulation in the immune and tumor microenvironment. Frontiers in immunology. 10:1078.
[DOI][PubMed][PMC]
Hughey J. J., Rhoades S. D., Fu D. Y., Bastarache L., Denny J. C. and Chen Q. 2019. Cox regression increases power to detect genotype-phenotype associations in genomic studies using the electronic health record. BMC Genomics. 20:1-7.
[DOI][PubMed][PMC]
Jaśkiewicz A., Pająk B. and Orzechowski A. 2018. The many faces of Rap1 GTPase. International journal of molecular sciences. 19(10):2848.
[DOI][PubMed][PMC]
Kanehisa M. and Goto S. 2000. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28(1):27-30.
[DOI][PubMed][PMC]
Kim N. L., Kim H. S., Kim D. H., Lee N. S., Kim S. K. and Min B. H. 2023. Value Chain Analysis of the Olive Flounder Paralichthys olivaceus Aquaculture Indusctry. Korean Journal of Fisheries and Aquatic Sciences. 56(6):930-935.
Kim W., Kim S., Kim D., Kim J., Park M., Kitamura S., Kim H., Kim D., Han H., Jung S. and Oh M. 2009. An outbreak of VHSV (viral hemorrhagic septicemia virus) infection in farmed olive flounder Paralichthys olivaceus in Korea. Aquaculture. 296(1):165-168.
[DOI]
Lee J., Choi I. C., Kim K. T., Cho S. H. and Yoo J. Y. 2012. Response of dietary substitution of fishmeal with various protein sources on growth, body composition and blood chemistry of olive flounder (Paralichthys olivaceus, Temminck & Schlegel, 1846). Fish Physiol.Biochem. 38(3):735-744.
[DOI][PubMed]
Li H. 2013. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv preprint arXiv:1303.3997.
Li H., Handsaker B., Wysoker A., Fennell T., Ruan J., Homer N., Marth G., Abecasis G., Durbin R. and 1000 Genome Project Data Processing Subgroup. 2009. The sequence alignment/map format and SAMtools. Bioinformatics. 25(16):2078-2079.
[DOI][PubMed][PMC]
Liu F., Tang X., Sheng X., Xing J. and Zhan W. 2016. Edwardsiella tarda Outer Membrane Protein C: An Immunogenic Protein Induces Highly Protective Effects in Flounder (Paralichthys olivaceus) against Edwardsiellosis. International Journal of Molecular Sciences. 17(7)
[DOI][PubMed][PMC]
Lu F., Wang R., Xia L., Nie T., Gao F., Yang S., Huang L., Shao K., Liu J. and Yang Q. 2021. Regulation of IFN-Is by MEF2D promotes inflammatory homeostasis in microglia. Journal of Inflammation Research. :2851-2863.
[DOI][PubMed][PMC]
Mohanty B. R. and Sahoo P. K. 2007. Edwardsiellosis in fish: a brief review. J.Biosci. 32(3):1331-1344.
[DOI][PubMed]
Park S. B., Aoki T. and Jung T. S. 2012. Pathogenesis of and strategies for preventing Edwardsiella tarda infection in fish. Vet.Res. 43(1):67.
[DOI][PubMed][PMC]
Pfisterer K., Shaw L. E., Symmank D. and Weninger W. 2021. The extracellular matrix in skin inflammation and infection. Frontiers in cell and developmental biology. 9:682414.
[DOI][PubMed][PMC]
Preena P. G., Dharmaratnam A. and Swaminathan T. R. 2022. A peek into mass mortality caused by antimicrobial resistant Edwardsiella tarda in goldfish, Carassius auratus in Kerala. Biologia. 77(4):1161-1171.
[DOI][PubMed][PMC]
Sommerset I., Krossøy B., Biering E. and Frost P. 2005. Vaccines for fish in aquaculture. Expert review of vaccines. 4(1):89-101.
[DOI][PubMed]
Sun K., Wang H., Zhang M., Xiao Z. and Sun L. 2009. Genetic mechanisms of multi-antimicrobial resistance in a pathogenic Edwardsiella tarda strain. Aquaculture. 289(1-2):134-139.
[DOI]
Szeto A. C., Clark P. A., Ferreira A. C., Heycock M., Griffiths E. L., Jou E., Mannion J., Luan S., Storrar S. and Knolle M. D. 2024. Mef2d potentiates type-2 immune responses and allergic lung inflammation. Science. 384(6703):eadl0370.
[DOI][PubMed][PMC]
Tsai H., Hamilton A., Tinch A. E., Guy D. R., Bron J. E., Taggart J. B., Gharbi K., Stear M., Matika O. and Pong-Wong R. 2016. Genomic prediction of host resistance to sea lice in farmed Atlantic salmon populations. Genetics Selection Evolution. 48:1-11.
[DOI][PubMed][PMC]
Uffelmann E., Huang Q. Q., Munung N. S., De Vries J., Okada Y., Martin A. R., Martin H. C., Lappalainen T. and Posthuma D. 2021. Genome-wide association studies. Nature Reviews Methods Primers. 1(1):59.
[DOI]
Vaca D. J., Thibau A., Schütz M., Kraiczy P., Happonen L., Malmström J. and Kempf V. A. 2020. Interaction with the host: the role of fibronectin and extracellular matrix proteins in the adhesion of Gram-negative bacteria. Med.Microbiol.Immunol.(Berl.). 209(3):277-299.
[DOI][PubMed][PMC]
Van der Auwera G. A. and O’Connor B. D. 2020. Genomics in the cloud: using Docker, GATK, and WDL in Terra.
Vergadi E., Vaporidi K., Theodorakis E. E., Doxaki C., Lagoudaki E., Ieronymaki E., Alexaki V. I., Helms M., Kondili E. and Soennichsen B. 2014. Akt2 deficiency protects from acute lung injury via alternative macrophage activation and miR-146a induction in mice. The Journal of Immunology. 192(1):394-406.
[DOI][PubMed]
Vishnupriya V., Swaminathan T. R., Dharmarathnam A., Sharma S. R. K. and Preena P. G. 2024. Virulent and Multi-drug-Resistant Edwardsiella tarda Infection in Oscar Fish: Unveiling the Threat of Mass Mortality and AMR Dissemination. Curr.Microbiol. 81(7):174.
[DOI][PubMed]
Wang Q., Yang M., Xiao J., Wu H., Wang X., Lv Y., Xu L., Zheng H., Wang S., Zhao G., Liu Q. and Zhang Y. 2009. Genome Sequence of the Versatile Fish Pathogen Edwardsiella tarda Provides Insights into its Adaptation to Broad Host Ranges and Intracellular Niches. PLOS ONE. 4(10):e7646.
[DOI][PubMed][PMC]
Wong C. H., Jenne C. N., Petri B., Chrobok N. L. and Kubes P. 2013. Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance. Nat.Immunol. 14(8):785-792.
[DOI][PubMed][PMC]
Xia F., Chen H., Jin Z. and Fu Z. 2021. Apelin-13 protects the lungs from ischemia-reperfusion injury by attenuating inflammatory and oxidative stress. Hum.Exp.Toxicol. 40(4):685-694.
[DOI][PubMed]
Xiao J., Wang Q., Liu Q., Wang X., Liu H. and Zhang Y. 2008. Isolation and identification of fish pathogen Edwardsiella tarda from mariculture in China. Aquacult.Res. 40(1):13-17.
[DOI]
Xie Z., Bailey A., Kuleshov M. V., Clarke D. J., Evangelista J. E., Jenkins S. L., Lachmann A., Wojciechowicz M. L., Kropiwnicki E. and Jagodnik K. M. 2021. Gene set knowledge discovery with Enrichr. Current protocols. 1(3):e90.
[DOI][PubMed][PMC]
Yin L., Zhang H., Tang Z., Xu J., Yin D., Zhang Z., Yuan X., Zhu M., Zhao S., Li X. and Liu X. 2021. rMVP: A Memory-efficient, Visualization-enhanced, and Parallel-accelerated Tool for Genome-wide Association Study. Genomics, proteomics & bioinformatics. 19(4):619-628.
[DOI][PubMed][PMC]
Yoshida G. M., Bangera R., Carvalheiro R., Correa K., Figueroa R., Lhorente J. P. and Yáñez J. M. 2018. Genomic prediction accuracy for resistance against Piscirickettsia salmonis in farmed rainbow trout. G3: Genes, Genomes, Genetics. 8(2):719-726.
[DOI][PubMed][PMC]
Yuan Y., Wang W., Zhang Y., Hong Q., Huang W., Li L., Xie Z., Chen Y., Li X. and Meng Y. 2022. Apelin-13 attenuates lipopolysaccharide-induced inflammatory responses and acute lung injury by regulating PFKFB3-driven glycolysis induced by NOX4-dependent ROS. Journal of Inflammation Research. :2121-2139.
[DOI][PubMed][PMC]
Zhu M., Foreman D. P., O’Brien S. A., Jin Y. and Zhang W. 2018. Phospholipase D in TCR-mediated signaling and T cell activation. The Journal of Immunology. 200(6):2165-2173.
[DOI][PubMed][PMC]
Zhu Q., Yamakuchi M., Ture S., de la Luz Garcia-Hernandez M., Ko K. A., Modjeski K. L., LoMonaco M. B., Johnson A. D., O’Donnell C. J. and Takai Y. 2014. Syntaxin-binding protein STXBP5 inhibits endothelial exocytosis and promotes platelet secretion. J.Clin.Invest. 124(10):4503-4516.
[DOI][PubMed][PMC]