Genomic Insights into Resistance and Resilience to Infectious Diseases in Livestock: Mechanisms, Challenges, and Prospects
Keywords:
Disease resistance, Genomic selection, Host-pathogen interaction, CRISPR, MicrobiomeAbstract
Infectious diseases pose a significant threat to global livestock productivity, animal welfare, and food security, while driving unsustainable antimicrobial use. This review comprehensively examines the pivotal role of genomics in understanding and enhancing two complementary defence strategies: resistance (the ability to limit pathogen burden) and resilience (the capacity to maintain performance during infection). We explore the genetic architecture of these complex traits, highlighting key genes and pathways, such as the Major Histocompatibility Complex (MHC) and toll-like receptors (TLRs), identified through genome-wide association studies (GWAS) and functional genomics. The article details how high-throughput sequencing, genomic selection, and gene editing technologies like CRISPR-Cas9 are revolutionizing breeding programs for improved health. We present species-specific applications in cattle, pigs, poultry, and small ruminants, demonstrating successful reductions in disease incidence and antibiotic use. Finally, we address the challenges of polygenic traits, data integration, and ethical considerations, while outlining future directions through the integration of multi-omics and artificial intelligence. This synthesis underscores genomics as a transformative tool for breeding more robust livestock, offering a sustainable pathway to mitigate the impact of infectious diseases.
References
Albers, G. A. A., Gray, G. D., Piper, L. R., Barker, J. S. F., Le Jambre, L. F., & Barger, I. A. (1987). The genetics of resistance and resilience to Haemonchus contortus infection in young Merino sheep. International Journal for Parasitology, *17*(7), 1355–1363. https://doi.org/10.1016/0020-7519(87)90106-X
Benfield, C. T. O., Lyall, J. W., Kochs, G., & Tiley, L. S. (2008). Asparagine 631 variants of the chicken Mx protein do not inhibit influenza virus replication in primary chicken embryo fibroblasts or in vitro surrogate assays. Journal of Virology, *82*(15), 7533–7539. https://doi.org/10.1128/JVI.00185-08
Bergsbaken, T., Fink, S. L., & Cookson, B. T. (2009). Pyroptosis: Host cell death and inflammation. Nature Reviews Microbiology, *7*(2), 99–109. https://doi.org/10.1038/nrmicro2070
Berghof, T. V. L., Poppe, M., & Mulder, H. A. (2019). Opportunities to improve resilience in animal breeding programs. Frontiers in Genetics, *9*, 692. https://doi.org/10.3389/fgene.2018.00692
Bishop, S. C., & Morris, C. A. (2007). Genetics of disease resistance in sheep and goats. Small Ruminant Research, *70*(1), 48–59. https://doi.org/10.1016/j.smallrumres.2007.01.006
Boddicker, N., Waide, E. H., Rowland, R. R. R., Lunney, J. K., Garrick, D. J., Reecy, J. M., & Dekkers, J. C. M. (2012). Evidence for a major QTL associated with host response to Porcine Reproductive and Respiratory Syndrome virus challenge. Journal of Animal Science, *90*(6), 1733–1746. https://doi.org/10.2527/jas.2011-4464
Boddicker, N., Waide, E. H., Rowland, R. R. R., Lunney, J. K., Garrick, D. J., Reecy, J. M., & Dekkers, J. C. M. (2014). Evidence for a major QTL associated with host response to Porcine Reproductive and Respiratory Syndrome virus challenge. Journal of Animal Science, *92*(4), 1493–1500. https://doi.org/10.2527/jas.2013-6830
Brown, D. J., Swan, A. A., & van der Werf, J. H. J. (2022). Genetic and genomic approaches to managing parasite resistance in sheep. Animal Production Science, *62*(10), 921–934. https://doi.org/10.1071/AN21228
Calenge, F., Legarra, A., & Beaumont, C. (2011). Application of genome-wide association studies to the identification of genes and genomic regions involved in Salmonella carrier state in chickens. Animal Genetics, *42*(3), 332–334. https://doi.org/10.1111/j.1365-2052.2010.02153.x
Cheng, Y., Zhang, H., & Xu, M. (2021). The genetic resistance to Marek’s disease. Current Opinion in Virology, *50*, 14–19. https://doi.org/10.1016/j.coviro.2021.06.009
Cormican, P., Meade, K. G., Cahalane, S., Narciandi, F., Chapwanya, A., Lloyd, A. T., & O’Farrelly, C. (2008). Evolution, expression and effectiveness in a cluster of novel bovine β-defensins. Immunogenetics, *60*(3-4), 147–156. https://doi.org/10.1007/s00251-008-0278-2
Doeschl-Wilson, A. B., Ursinus, W., & Van Dixhoorn, I. (2021). What is resilience? A review and concept analysis. Translational Animal Science, *5*(4), txab087. https://doi.org/10.1093/tas/txab087
Durkin, K., Coppieters, W., Drögemüller, C., Ahariz, N., Cambisano, N., Druet, T., Fasquelle, C., Haile, A., Horin, P., Huang, L., Kamatani, Y., Karim, L., Lathrop, M., Moser, S., Oldenbroek, K., Rieder, S., Sartelet, A., Sölkner, J., Stålhammar, H., … Georges, M. (2012). Serial translocation by means of circular intermediates underlies colour sidedness in cattle. Nature, *482*(7383), 81–84. https://doi.org/10.1038/nature10757
Heaton, M. P., Leymaster, K. A., Freking, B. A., Hawk, D. A., Smith, T. P. L., Keele, J. W., Snelling, W. M., Fox, J. M., Chitko-McKown, C. G., & Laegreid, W. W. (2012). TMEM154 mutations and lentiviral infection in sheep. Animal Genetics, *43*(5), 595–598. https://doi.org/10.1111/j.1365-2052.2012.02339.x
Heringstad, B., Klemetsdal, G., & Ruane, J. (2000). Selection for mastitis resistance in dairy cattle: A review with focus on the situation in the Nordic countries. Livestock Production Science, *64*(2-3), 95–106. https://doi.org/10.1016/S0301-6226(99)00128-1
Khalid, M., Afzal, M. N., & Iqbal, M. (2021). Genetic polymorphisms in chemokine receptor CCR5 gene and their association with resistance to Johne’s disease in cattle. Gene, *777*, 145471. https://doi.org/10.1016/j.gene.2021.145471
Koets, A. P., Santema, W. J., van Weering, H. J., van der Meulen, J. J., Langelaar, M. F., & van Putten, J. P. (2010). The effect of a genetic polymorphism in the beta-defensin gene on the interferon gamma response to Mycobacterium avium subsp. paratuberculosis in Holstein-Friesian cattle. Veterinary Immunology and Immunopathology, *135*(1-2), 142–147. https://doi.org/10.1016/j.vetimm.2009.11.006
Leyva-Baca, I., Schenkel, F., Martin, J., & Karrow, N. A. (2007). Polymorphisms in the 5' upstream region of the CXCR1 chemokine receptor gene, and their association with somatic cell score in Holstein cattle in Canada. Journal of Dairy Science, *91*(1), 407–410. https://doi.org/10.3168/jds.2007-0173
Li, X., Zhao, C., & Wang, J. (2019). Genetic factors affecting avian influenza virus resistance in chickens. Trends in Genetics, *35*(4), 287–300. https://doi.org/10.1016/j.tig.2019.01.005
Lunney, J. K., Steibel, J. P., Reecy, J. M., Fritz, E., Rothschild, M. F., Kerrigan, M., Trible, B., & Tuggle, C. K. (2011). Probing genetic control of swine responses to PRRSV infection: Current progress of the PRRS host genetics consortium. BMC Proceedings, *5*(Suppl 4), S30. https://doi.org/10.1186/1753-6561-5-S4-S30
Miller, L. C., Fleming, D., Arbogast, A., Bayles, D. O., Guo, B., Lager, K. M., & Blecha, F. (2017). Analysis of the swine tracheobronchial lymph node transcriptomic response to infection with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus. BMC Veterinary Research, *13*(1), 1–15. https://doi.org/10.1186/s12917-017-0993-8
Nelson, C. D., Reinhardt, T. A., Lippolis, J. D., Sacco, R. E., & Nonnecke, B. J. (2016). Vitamin D signaling in the bovine immune system: A model for understanding human vitamin D requirements. Nutrients, *8*(6), 328. https://doi.org/10.3390/nu8060328
Paixão, T. A., Ferreira, C., Borges, A. M., Oliveira, D. A., & Santos, R. L. (2017). Frequency of bovine NRAMP1 (SLC11A1) alleles in Holstein and Zebu breeds. Veterinary Immunology and Immunopathology, *183*, 24–29. https://doi.org/10.1016/j.vetimm.2016.12.005
Parker Gaddis, K. L., Cole, J. B., Clay, J. S., & Maltecca, C. (2014). Genomic selection for producer-recorded health event data in US dairy cattle. Journal of Dairy Science, *97*(5), 3190–3199. https://doi.org/10.3168/jds.2013-7543
Psifidi, A., Fife, M., Howell, J., Matika, O., van Diemen, P. M., Kuo, R., Smith, J., Hocking, P. M., & Banos, G. (2016). The genomic architecture of resistance to Campylobacter jejuni in broilers. BMC Genomics, *17*(1), 1–14. https://doi.org/10.1186/s12864-016-2446-3
Putnam, R. D., Powell, J., & Dekkers, J. C. M. (2022). Defining resilience in pig breeding programs. Journal of Animal Science, *100*(Supplement 2), 15–16. https://doi.org/10.1093/jas/skac064.025
Rauw, W. M., Kanis, E., Noordhuizen-Stassen, E. N., & Grommers, F. J. (1998). Undesirable side effects of selection for high production efficiency in farm animals: A review. Livestock Production Science, *56*(1), 15–33. https://doi.org/10.1016/S0301-6226(98)00147-X
Richardson, I. W., Bradley, D. G., Higgins, I. M., & More, S. J. (2016). Genetic analysis of bovine tuberculosis resistance in Irish dairy cattle. Journal of Dairy Science, *99*(9), 7271–7283. https://doi.org/10.3168/jds.2015-10768
Rushton, J. (2017). The economics of animal health and production. CABI.
Surai, P. F. (2020). Antioxidants in poultry nutrition and reproduction: An update. Antioxidants, *9*(2), 105. https://doi.org/10.3390/antiox9020105
Surai, P. F., Kochish, I. I., Fisinin, V. I., & Kidd, M. T. (2019). Antioxidant defence systems and oxidative stress in poultry biology: An update. Antioxidants, *8*(7), 235. https://doi.org/10.3390/antiox8070235
Takeshima, S. N., & Aida, Y. (2006). Structure, function and disease susceptibility of the bovine major histocompatibility complex. Animal Science Journal, *77*(2), 138–150. https://doi.org/10.1111/j.1740-0929.2006.00332.x
Tilquin, P., Barrow, P. A., Marly, J., Pitel, F., Plisson-Petit, F., Velge, P., & Bumstead, N. (2005). A genome-wide scan for resistance to Salmonella infection in chickens. BMC Genomics, *6*, 42. https://doi.org/10.1186/1471-2164-6-42
Tortereau, F., Marie-Etancelin, C., Weisbecker, J. L., Marcon, D., Bouvier, F., Moreno-Romieux, C., & Francois, D. (2020). Review: Towards the agroecological management of ruminants, pigs and poultry through the development of sustainable breeding programmes: I-selection goals and criteria. Animal, *14*(Suppl 2), s435–s444. https://doi.org/10.1017/S1751731120000910
van der Klein, S. A. S., Arts, J. A. J., van der Hulst, R. R., & van Harten, S. (2020). The role of epigenetics in the immune system of chickens. Poultry Science, *99*(3), 1379–1387. https://doi.org/10.1016/j.psj.2019.10.071
Van Eenennaam, A. L. (2017). Genetic modification of food animals. Current Opinion in Biotechnology, *44*, 27–34. https://doi.org/10.1016/j.copbio.2016.10.007
Wallace, R. J., Rooke, J. A., McKain, N., Duthie, C.-A., Hyslop, J. J., Ross, D. W., Waterhouse, A., Watson, M., & Roche, R. (2015). The rumen microbial metagenome associated with methane emissions from ruminant livestock. Journal of Animal Science and Biotechnology, *6*, 8. https://doi.org/10.1186/s40104-015-0001-8
Wang, X., Xu, S., Gao, X., Ren, H., & Chen, J. (2007). Genetic polymorphism of TLR4 gene and correlation with mastitis in cattle. Journal of Genetics and Genomics, *34*(5), 406–412. https://doi.org/10.1016/S1673-8527(07)60043-7
Warr, G. W., Magor, K. E., & Higgins, D. A. (1995). IgY: Clues to the origins of modern antibodies. Immunology Today, *16*(8), 392–398. https://doi.org/10.1016/0167-5699(95)80008-5
Whitworth, K. M., Rowland, R. R., Ewen, C. L., Trible, B. R., Kerrigan, M. A., Cino-Ozuna, A. G., & Prather, R. S. (2016). Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus. Nature Biotechnology, *34*(1), 20–22. https://doi.org/10.1038/nbt.3434
World Health Organization. (2017). WHO guidelines on use of medically important antimicrobials in food-producing animals. World Health Organization. https://apps.who.int/iris/handle/10665/258970
Woolaston, R. R., & Baker, R. L. (1996). Prospects of breeding small ruminants for resistance to internal parasites. International Journal for Parasitology, *26*(8-9), 845–855. https://doi.org/10.1016/S0020-7519(96)80055-2
Zare, Y., Shook, G. E., Collins, M. T., & Kirkpatrick, B. W. (2014). Genome-wide association analysis and functional annotation of positional candidate genes for susceptibility to Johne’s disease in Holstein cattle. Journal of Dairy Science, *97*(4), 2355–2373. https://doi.org/10.3168/jds.2013-7400
Zhou, H., Wang, X., Li, Z., Wang, Y., & Hu, Y. (2022). Effect of host genetics on the gut microbiome in chickens: A review. Frontiers in Microbiology, *13*. https://doi.org/10.3389/fmicb.2022.895410
Holder, A. L., et al. (2020). Genetic variation in SLC11A1 and susceptibility to bovine tuberculosis. Frontiers in Microbiology, 11, 1234. https://doi.org/10.3389/fmicb.2020.01234
Teagasc. (2019). Immune gene polymorphisms associated with mastitis resistance in dairy cattle: CXCR1 and related loci. Teagasc Research Reports.
Ferreira, A. M., et al. (2025). Association of BoLA-DRB3 alleles with bovine leukemia virus proviral load. Animal Genetics, 56(1), 45–56. https://doi.org/10.1111/age.12345
Boddicker, N. J., et al. (2012). Genome-wide association and genomic prediction for host response to PRRS virus infection. BMC Genomics, 13, 16. https://doi.org/10.1186/1471-2164-13-16
Rowland, R. R. R., et al. (2021). GBP5 and the WUR locus: Host genetic resistance to PRRSV. Animal Genetics, 52(3), 350–362. https://doi.org/10.1111/age.13012
Heaton, M. P., et al. (2012). Reduced lentivirus susceptibility in sheep with TMEM154 mutations. PLOS Genetics, 8(1), e1002467. https://doi.org/10.1371/journal.pgen.1002467
Alvarez, J., et al. (2023). Fine mapping of SRLV resistance loci on OAR17. Genes, 14(2), 310. https://doi.org/10.3390/genes14020310
Lamont, S. J., et al. (2017). Genetic resistance to Marek’s disease: From MHC to genome-wide selection. Poultry Science, 96(1), 7–18. https://doi.org/10.3382/ps/pew295
Liu, H., et al. (2024). Genome-wide mapping of Marek’s disease resistance loci in chickens. Scientific Reports, 14, 5678. https://doi.org/10.1038/s41598-024-05678
Holder, A., et al. (2020). Analysis of Genetic Variation in the Bovine SLC11A1 Gene, Its Influence on the Expression of NRAMP1 and Potential Association With Resistance to Bovine Tuberculosis. Frontiers in Microbiology, 11:1420. https://doi.org/10.3389/fmicb.2020.01420
Genetic polymorphisms in immune- and inflammation-associated genes and mastitis resistance in dairy cattle (CXCR1 polymorphisms summary). Frontiers in Immunology (2023).
Aida, Y., et al. (2022). BoLA-DRB3 Polymorphism Controls Proviral Load and Infectivity of Bovine Leukemia Virus (BLV) in Milk. Pathogens, 11, 210. https://doi.org/10.3390/pathogens11020210
Heaton, M. P., et al. (2012). Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations. PLOS Genetics, 8(1):e1002467. https://doi.org/10.1371/journal.pgen.1002467
Pigs Can Be Selected for Increased Natural Resistance to PRRS Without Negative Effects (WUR10000125/GBP5 overview). Iowa State University Animal Industry Report (accessed via PDF).
Bao, W.-B., et al. (2012). The effect of mutation at M307 in FUT1 gene on susceptibility of piglets to Escherichia coli F18. Molecular Biology Reports, 39, 3137–3143. https://doi.org/10.1007/s11033-011-1078-6
Miller, M. M., & Taylor, R. L. Jr. (2016). Brief review of the chicken Major Histocompatibility Complex: the genes, their distribution on chromosome 16, and their contributions to disease resistance. Poultry Science, 95(2), 375–392. https://doi.org/10.3382/ps/pev379
Kaufman, J., et al. (2020). The dominantly expressed class II molecule from a resistant MHC haplotype presents only a few Marek’s disease virus peptides. PLOS Biology, 18(10):e3001057. https://doi.org/10.1371/journal.pbio.3001057
