Review of Research Progress on Pig Disease-Resistance Breeding Technology

High-yield objectives usually lead to reduced pig resistance. At the same time, pig farm diseases, especially viral infectious diseases, severely threaten pig health. Although vaccination has played an important preventive and control role, it has not been able to completely control and eliminate the prevalence of infectious diseases. In the long run, adopting genetic methods to improve pigs' resistance to pathogens at the genetic level, and carrying out disease-resistance breeding, has a fundamental effect. In the 1930s, some scholars reported that different chicken breeds differed in susceptibility to Marek's disease, and in the subsequent period fairly systematic research was conducted on disease-resistance breeding in pigs and other livestock and poultry. With the development of immunology and biological products science, most infectious diseases were effectively controlled through vaccination, causing disease-resistance breeding to be somewhat neglected. Since the 1980s, with the development of molecular biology and genetic engineering technology, new ideas have been provided for disease-resistance breeding, and people have once again attached importance to research on disease-resistance breeding.

1 Genetic Basis of Disease Resistance During the infection process, pathogens encounter 3 defense mechanisms, namely the epithelial defense mechanism, the non-specific defense mechanism and the specific defense mechanism. When an individual is infected by a pathogen, these 3 aspects of defense mechanisms are mobilized to resist it. Whether a pig develops disease depends on the result of the interaction between infection and defense function; pigs with strengthened defense function exhibit natural disease resistance. According to differences in genetic basis, disease resistance can be divided into specific disease resistance and general disease resistance. Specific disease resistance refers to a pig's resistance to a particular disease or pathogen; this resistance is mainly controlled by one major gene locus, and can also be affected to varying degrees by other loci (including regulators) and environmental factors. Existing research results indicate that the intrinsic mechanism of specific disease resistance lies in the presence or absence of a certain molecule or its variant in the host body; this molecule has the following effects:

①Determines allogeneic recognition and specific allogeneic reactions;

②Determines the specific adhesion of the pathogen;

③After the pathogen enters the body, it proliferates in the body, determining whether it can cause disease in the host. General disease resistance is not limited to resistance to a certain pathogen; it is affected by the combined influence of multiple genes and the environment. Differences in pathogen antigenicity have very little effect on general disease resistance, or even no effect at all. This kind of disease resistance reflects the body's overall defense function against disease. For example, the chicken's MHC is related to resistance and susceptibility to Marek's disease, coccidiosis and Rous sarcoma and other diseases.

1.1 MHC and disease resistance The major histocompatibility complex (Major Histocompatibility Complex, MHC) is a group of gene clusters closely related to disease resistance and immune response, encoding cell surface specific proteins, and exists in all higher animals. MHC encodes 3 classes of genes; these genes are tightly linked on autosomes to form haplotypes and are inherited as autosomal codominant traits. The pig's MHC (named SLA) is located on pig chromosome 7 (Warner, 1987), and includes type I and type II genes, among which type I genes have extremely strong polymorphism. The SLA complex is closely related to immune response. Rothschild et al. (1984) confirmed that the immune response of 5 American pig breeds to Bordetella bronchiseptica is under the control of SLA. Mallard et al. (1989) found in NIH-type pigs that individuals with SLA genotypes dd, dg and SS are strong responders to sheep red blood cells, hen egg white lysozyme and the synthetic peptide (T,G)-A-L. In terms of disease resistance, Tissot et al. (1989) found that hereditary cutaneous malignant melanoma is related to the SLA complex. Renard et al. (1985) found that pre-weaning mortality caused by diarrhea is related to the haplotype type of SLA. In addition, different SLA haplotypes also differ in type with respect to resistance to parasites (Lunney et al., 1988). Warner (1991) comparatively completely listed the associations with diseases as well as the binding and functions of the SLA complex, and Lunney et al. (1998) and Valman et al. (1998) updated this again.

1.2 Major disease-resistance genes Specific disease resistance is controlled by major genes with specific resistance to a certain disease or pathogen. Identifying such specific disease-resistance genes is of great significance for disease-resistance breeding; it not only allows direct major-gene selection for disease-resistance breeding, but can also further enable the breeding of transgenic animals. The more clearly studied examples are the pig Escherichia coli K88 and F18 receptor genes. Diarrhea in newborn piglets is caused by the cell surface antigen of the K88 strain attaching to the corresponding receptor on the surface of small intestinal mucosal epithelial cells; this bacterium binds to the receptor and proliferates in large numbers, releasing enterotoxin and causing diarrhea. Piglets lacking the K88 receptor can resist K88 adhesion, and thus can resist diarrhea (Sellwood, 1975). The K88 receptor gene is located on pig chromosome 13 (Rothschild, 1992); the presence or absence of its receptor is controlled by a pair of alleles S and s, with the presence of the receptor (S) completely dominant over the absence of the receptor (s), showing Mendelian inheritance. The frequency of K88-positive pigs is very high in countries around the world; for example, K88-positive pigs in Australia accounted for 88% of the studied Large White and Landrace populations (Sondgrass et al., 1981), while the frequency of the K88 receptor in Chinese local pigs is very low, giving them natural disease resistance (Chappuls, 1984). Bertschinser (1983) found that pre- and post-weaning piglet edema disease is caused by the F18 strain binding to cell surface receptors and releasing enterotoxin, and piglets lacking the normal F18 receptor can resist diarrhea and edema disease. The F18 receptor gene is located on pig chromosome 6 and is closely linked with blood group inhibitor S, the erythrocyte enzyme system and the halothane gene. The receptor gene that can bind to F18 adhesin is expressed as a susceptibility gene and shows dominant inheritance; otherwise it is a resistance gene, that is, recessive inheritance (Vogeli et al., 1992). Vogeli (1997) again used the candidate gene method and linkage analysis method to study the alpha(1,2) fucosyltransferase genes FUTI and FUTZ located in the 6qll region as 1 candidate gene controlling F18 adhesion. In addition, the major gene related to disease resistance and the E. coli F4 receptor gene located in the 13q31 region are also related to pig diarrhea.

1.3 Relationship among disease resistance, immune response and production traits Experimental evidence on the relationship among disease resistance, immune response capacity and production performance is still very lacking, and results are inconsistent. Vander et al. (1983) found that selection for high productivity increased susceptibility to Marek's disease, while Lamont et al. (1989) found that the relationship between Marek's disease and egg-laying performance was negatively correlated. In pigs, Meeker et al. (1987) found that growth rate was negatively correlated with immune response after vaccination with commercial Bordetella bronchiseptica vaccine or pseudorabies virus vaccine; pigs with the intestinal K88 receptor grew faster and had better feed utilization (Edfors et al., 1986). The SLA of pigs is linked with many production traits (Warner et al., 1991; Lunney et al., 1998). These results, together with the fact that the associations between pig SLA and growth, backfat and reproductive traits are mostly positive, indicate that SLA genes should be the preferred genes for disease-resistance breeding in the future. Mallard et al. (1998), in pig high immune response (H line) and low immune response (L line) strains formed after 8 generations of selection, found that the H line reached market weight 10 d earlier than the L line.