Dr Craig Lewis & Dr Andrey Pavlov – PIC
Disease remains one of, or THE dominant constraints on economic and sustainable pig production worldwide.
Endemic and transboundary pathogens reduce biological efficiency, compromise animal welfare, impact trade / operations, increase antimicrobial use, and elevate the environmental footprint of pork production. As expectations rise around sustainability, genetics has emerged as a critical, long-term lever for improving disease outcomes.
Rather than selecting against individual pathogens, modern breeding to date has increasingly emphasized robustness and resilience – integrated traits that allow pigs to maintain productivity under health and environmental challenges.
Why disease resilience matters in pig production
Robustness is typically defined as the ability of an animal to perform consistently across variable environments or conditions, while resilience refers to the capacity to withstand, adapt to, and recover from disturbances such as infectious disease. These traits reflect complex biological processes involving immune regulation, metabolism, and stress physiology, and are therefore polygenic and lowly to moderately heritable. Importantly, resilience does not necessarily imply reduced pathogen load; instead, it often reflects tolerance, where performance losses are minimized despite ongoing infection.
From a breeding perspective, robustness and resilience are most effectively captured through large-scale data recorded under commercial conditions. Survival, lifetime productivity, variability in growth rate, and treatment records can all function as proxy indicators of disease tolerance. Genomic selection has substantially increased the effectiveness of such approaches by enabling accurate breeding value estimation even when direct disease challenge data are limited. As a result, many modern pig breeding programs now explicitly include robustness or resilience objectives alongside growth, efficiency, and carcass traits.
The practical value of such improvement extends beyond health alone. Increased resilience can translate into improved feed efficiency, reduced mortality, lower treatment costs, improved lifetime productivity, and reduced environmental impact per kilogram of pork produced. In this way, genetic improvement contributes not only to biological performance, but also to economic sustainability and resource-use efficiency within modern pig production systems.
Tolerance versus resistance: what genetics can deliver
Framing disease resistance in terms of tolerance rather than absolute resistance has proven particularly valuable for endemic pathogens. Complete resistance is rare, slow to achieve through conventional selection, and may impose biological trade-offs. Tolerance-based approaches accept ongoing exposure but aim to decouple infection from poor outcomes.
It should however be noted that naturally occurring single gene resistance mechanisms do already exist in pigs, illustrating that decisive genetic solutions to disease are biologically plausible. A well-established example is resistance to Escherichia coli expressing F4 and F18 fimbriae, major causes of post weaning diarrhoea. A polymorphism in the FUT1 gene, which controls expression of intestinal epithelial receptors, determines whether F18 fimbriae can bind to the gut surface. Pigs homozygous for the resistant FUT1 allele lack the functional receptor and are effectively resistant to F18 positive E. coli infection, with no consistent negative effects on growth or reproduction. This naturally occurring, single gene solution has been successfully integrated into commercial breeding programs, providing durable health benefits under field conditions.
PRRS as a case study for genetic resilience
With no specific genes for resistance identified Porcine reproductive and respiratory syndrome (PRRS) exemplifies both the opportunities and limitations of breeding for disease resistance in terms of tolerance rather than absolute resistance. PRRS has become the most intensively studied model for genetic resilience in pigs.
PRRS has had a profound global impact since its emergence in the late 1980s. The virus reduces reproductive performance in breeding herds and increases mortality, reduces growth rate, and impairs feed efficiency in growing pigs. Its significant economic cost has been repeatedly documented, but more recent work highlights an additional consequence: reduced production efficiency increases greenhouse gas emissions per kilogram of pork produced.
Large-scale life cycle assessment has shown that PRRS-negative pig production systems have a 4–6% lower environmental impact than industry-average systems and a 9–17% lower impact than PRRS-positive systems. These effects are driven primarily by higher survival and improved feed conversion, illustrating how genetic and health interventions that enhance resilience deliver climate and resource-use co-benefits.
Genetic studies under experimental and commercial PRRS challenge demonstrated that host response has a clear heritable component, particularly in nursery pigs. Identification of a major quantitative trait locus on chromosome 4, associated with variation in the GBP5 gene, provided the first widely adopted marker for PRRS resilience. Pigs carrying the favourable allele show reduced viremia and improved growth under PRRS challenge, validating the principle that genetic tolerance can be selected for at scale.
However, subsequent work also revealed important limitations. Effects of single loci vary across viral strains, production stages, and health status, and in some cases may be neutral or even unfavourable under PRRS-free conditions. These findings underline that PRRS response is polygenic and context-dependent, reinforcing the need for whole-genome selection within robust breeding frameworks rather than reliance on individual markers.
Gene editing and the potential for true disease resistance
While PRRS genetics has largely focused on tolerance, gene editing has demonstrated that true resistance is biologically feasible. Editing of the CD163 receptor, which PRRS virus uses to enter macrophages, produces pigs that are resistant to infection without observable adverse effects on health or performance. More specifically, gene editing technology such as CRISPR enabled precise modification of the specific domain of the CD163 receptor used by the virus for entry into host cells, while maintaining the receptor’s normal biological functions. This is a major step forward, as it effectively prevents infection rather than treating disease, clearly demonstrating how targeted genetic approaches can improve disease resilience.
To breed pigs that are resistant to PRRS, researchers precisely removed a portion of a specific gene that the PRRS virus uses to infect the pig. Nothing foreign was added and no genes were inserted. This distinction is important when considering the broader discussion surrounding gene editing technologies.
Gene editing is not the same as genetic modification
A clear distinction exists between genetically modified organisms (GMOs) and gene-edited animals. Gene editing technologies such as CRISPR make precise, targeted changes within an animal’s existing DNA without introducing foreign genetic material. In contrast, traditional GMOs typically involve inserting genes from another species, such as bacterial genes in Bt crops or growth hormone genes in salmon, to introduce new traits. This distinction is important, as gene-edited animals—such as PRRS-resistant pigs—are not transgenic but are created by modifying their own genome. Recognizing this difference supports clearer scientific communication and may improve public understanding and acceptance of gene-editing technologies in agriculture.
Gene-editing technology shows strong potential to address both agricultural challenges and human health conditions. To date, it has been successfully used to treat patients with disorders such as sickle cell anaemia, inherited hearing loss, and certain forms of inherited blindness. In addition, gene-editing therapies are currently in development for conditions including HIV, cystic fibrosis, and various cancers, according to the World Health Organization.
Gene editing raises questions that extend beyond scientific feasibility. Regulatory frameworks, societal acceptance, and implications for international trade will determine whether such technologies can be deployed commercially. Nevertheless, PRRS provides a proof of concept for how functional genomics could transform disease control if these barriers are addressed.
What PRRS can teach us about ASF and FMD
Connecting to current breeding, the FUT1 case above reinforces a key principle emerging from PRRS and gene editing research: when infection depends on a specific host receptor, genetics can break the disease pathway entirely, whether through conventional selection or targeted genome modification.
Looking forward, these lessons are highly relevant to transboundary diseases such as African swine fever (ASF) and foot-and-mouth disease (FMD). ASF, in particular, causes near-complete mortality in naïve populations, leaving little scope for tolerance-based selection. Although no functional resistance genes have yet been identified, advances in understanding host–pathogen interactions, combined with genome editing tools, may eventually allow modification of critical entry receptors or immune pathways.
For FMD, where vaccination remains effective but logistically challenging, genetic approaches enhancing resilience or shortening recovery could complement existing control strategies. In both cases, broader improvements in robustness—such as enhanced immune competence and stress tolerance—will remain valuable regardless of whether pathogen-specific resistance becomes achievable.
Genetics as part of future disease control
In summary, genetics for disease control in pigs is evolving from broad selection for robustness, through tolerance-based resilience as exemplified by PRRS, toward the possibility of precise, gene-edited resistance. Together, these approaches offer a future in which disease impact can be reduced sustainably, supporting animal welfare, farm profitability, and environmental performance while strengthening preparedness for high-consequence diseases such as ASF and FMD.
This article was first published in PORCUS, the South African pig industry magazine, and has been adapted for publication on our websites.
References and further reading
Bishop SC, Woolliams JA. Genomics and disease resistance studies in livestock. Livest Sci. 2014;166:190–198.
Dekkers JCM, Rowland RRR, Lunney JK, Plastow GS. Host genetics of response to porcine reproductive and respiratory syndrome in nursery pigs. Vet Microbiol. 2017;209:107–113.
Thoma GJ, Galina Pantoja L, Linhares DCL, et al. The effects of PRRS on the environmental impact of pig production: a life cycle assessment study. Front Vet Sci. 2025;12:1625581.
Chase-Topping M, Plastow G, Dekkers JCM, et al. The WUR SNP and PRRS transmission. Genet Sel Evol. 2023;55:51.
Rowland RRR, Brandariz-Nuñez A. Role of CD163 in PRRSV infection. Virology. 2024;600:110262.
Petersen GEL, Buntjer JB, Byrne TJ, Doeschl-Wilson A. Modeling suggests gene editing combined with vaccination could eliminate a persistent disease in livestock. Proc Natl Acad Sci USA. 2022;119:e2107224119.
Kyriazakis I, Arndt C, Aubry A, et al. Improve animal health to reduce livestock emissions. Proc R Soc B. 2024;291:20240675.
You X, Li G, Lei Y, et al. Role of genetic factors in resistance and susceptibility to PRRSV. Virus Res. 2023;326:199057.