Background Disease resistance is the ability of a host to resist infection or exert control over the life cycle of a pathogen. There is evidence of genetic variation in response to disease for nearly every disease in livestock that has been thoroughly studied, supporting the utility of genomic selection to identify and breed livestock for increased natural disease resistance. This is an especially attractive disease control strategy when other (traditional) control methods, such as medication, sanitation, vaccination, or animal management strategies prove ineffective or impractical.
There are several benefits of selecting for increased disease resistance including: decreased impact on performance, decreased pathogen level, and decreased pathogen shedding. However, prior to implementing genetic selection for increased disease resistance, the following questions must be addressed:
• Is the disease of economic importance?
• Is there natural variation in host response to this disease?
• Which genes are associated with resistance to this disease?
• For this gene — what is the favorable allele for host response to infection?
• What is the effect of the favorable allele under alternate conditions?
An example of how these questions have been applied to investigate natural resistance to porcine reproductive and respiratory syndrome virus (PRRSV)-infection is outlined below:
Question #1: Is the disease is of economic importance? Yes, historically, PRRS is still considered the most costly disease in swine. Several factors contribute to the economic significance of PRRS, including the fact that PRRS can affect pigs during all stages of production, is difficult to control, and that no effective PRRS control strategy is currently available.
Question #2: Is there is natural variation in host response to this disease? Yes, the first indication of natural variation in host response to PRRSVinfection was the observation that some breeds appear better able to cope with PRRS than others. Such observations motivated the formation of the PRRS Host Genetics Consortium (PHGC) which was formed with the objective of using genomics to identify genes associated with PRRS resistance. To date, the PHGC has conducted over 20 trials in which commercial crossbred pigs were experimentally infected with PRRSV.
Question #3: Which genes are associated with resistance to this disease? Genomic regions associated with PRRS virus load (VL) and weight gain (WG) post-infection were identified by performing a genome-wide association study, which combines genetic information and trait information to identify chromosomal regions statistically associated with the trait of interest. Results showed that a region on chromosome 4 explained 16% and 11% of genetic variation in PRRS VL and WG, respectively. Within this region, a single genetic marker, referred to as WUR, is used to track the genetics of this region.
Question #4: For this gene — what is the favorable allele for host response to infection? For WUR, the B allele was associated with lower PRRS VL and higher WG and is, therefore, considered the favorable allele under PRRS challenge. The B allele is also the dominant allele, meaning that pigs with either the BB or AB genotype have increased PRRS resistance.
Question #5: What is the effect of the favorable allele under alternate conditions? This question was addressed by performing a number of follow-up studies, the first of which was conducted to estimate the effect of WUR following infection with a different isolate of PRRSV and with different commercial crosses. Results of these analyses showed that the B allele maintained its status as the favorable allele for PRRS VL and WG using different breed crosses, but that the effect on WG was not significant following infection with a different PRRSV isolate.
A second study was conducted to estimate the effect of WUR genotype on response to vaccination with a PRRS modified live virus (MLV) vaccine. Results from these analyses showed: 1.) no adverse effect of WUR on average daily gain (ADG) under normal, non-challenged conditions (i.e. when non-vaccinated); and 2.) that the B allele maintained its status as the favorable allele following PRRS MLV vaccination.
An additional experiment was conducted to investigate the effect of WUR following co-infection with another pathogen. Results of these analyses showed no significant effect of WUR on ADG. However, results for VL showed that the B allele maintained its status as the favorable allele following PRRS/porcine circovirus type 2b (PCV2b) co-infection.
A final study was conducted to estimate the effect of WUR on economically important traits under non-challenged conditions. It was particularly important to estimate the effect of WUR under this condition since it must be established that implementing selection based on a genetic marker for increased disease resistance will not negatively impact performance under non-challenged conditions. Records collected on Topigs Norsvin N (Landrace), Z (Large White), synthetic (Tempo), and Pietrain (Top Pi) lines were used to address this objective. Results showed no significant effect of WUR on overall economic value for any of these lines.
Conclusions Results from this case study show how a gene associated with increased natural resistance to PRRS was identified and validated under various challenged and non-challenged conditions. Taken together, results indicate that: 1.) selection based on WUR genotype can be used to breed pigs for improved natural resistance to PRRSV-infection; 2.) this approach can be used as a potential PRRS control strategy; and 3.) a similar approach can be applied to other diseases, examples of which could include: Escherichia coli, porcine epidemic diarrhea virus (PEDV), PCV2b, Pseudorabies, or Sarcocystis miescheriana, for which evidence of genetic variation in host response to disease challenge was observed for previous studies.
In closing, Topigs Norsvin has invested extensive resources to study natural disease resistance and continues to investigate ways to capitalize on naturally occurring genetic variation for host response to specific diseases such as PRRS and for general, overall robustness to disease challenge.