Increased selection pressure applied to commercially important
traits in production environments is often accompanied by increases
in disease problems. Cost estimates for swine diseases in the
U.S. exceed 1.5 billion dollars yearly. At the same time, selection
for immune responsiveness and disease resistance has often been
ignored by animal geneticists because of the difficulty of measuring
these traits. Actual disease resistance to individual diseases
would have to be measured under an environment that included disease
challenge. Such testing would be prohibitively expensive. New
opportunities to improve our understanding of the genetic nature
of disease resistance now exist through the recent advances in
molecular biology, gene mapping, and immunology and make selection
for disease resistance possible in the future. However, genetic
considerations involved with testing and selection for disease
resistance and improved immune responsiveness will require knowledge
of the genetic correlations between disease resistance and immune
responsiveness and production traits. Limited research suggests
that antagonistic relationships between immune response, disease
resistance, and production traits might make simultaneous improvement
of these traits difficult by conventional breeding and selection
methods. Use of marker-assisted selection or gene-transfer methods
with the genes of the MHC or other major genes may offer an alternative
approach for simultaneous improvements in all of these traits.
Efficient pork production is often disrupted by disease, which costs livestock producers and consumers billions of dollars each year. These considerable monetary losses result from mortality, subclinical losses due to poorer production efficiency, increased veterinary costs and product loss. Selection pressure on commercially important traits under stressful production settings also may increase the incidence of disease. Disease also impairs genetic improvement in production traits because efficiency of selection is reduced. Current methods to control disease include vaccination, medication, sanitation, and isolation of animals from pathogens and eradication of certain diseases. These approaches, however, are not always effective. Lack of effectiveness of some vaccines and increased attempts by consumers to change drug-use regulations because of fears of contamination of human food sources underscore the need for more effective methods to combat disease.
A clear understanding of disease and the animal's defense systems
is required for alternative approaches to disease control. The
onset of disease is often the result of the interaction between
an individual animal's genotype and the environment to which the
animal is exposed. If an animal has a genetic predisposition
for acquiring a disease, then environmental conditions, including
standard disease-prevention methods may be only partly effective
in preventing disease. An often-overlooked alternative approach
to standard disease control methods would be selective breeding
to increase disease resistance in livestock. Genetic resistance
to disease involves many facets of the body's defense system and
their interactions and is extremely complex.
In this report the current status of knowledge
of methods to select for disease resistance and immune responsiveness
in pigs and other livestock is reviewed. Opportunities to improve
disease resistance and immune responsiveness in pigs through marker-assisted
selection and gene-transfer techniques are discussed.
The presence of some diseases may result from strictly genetic
control, whereas others may be caused by a combination of genetic
predisposition and exposure to pathogens. Disease resistance
research has included measurement of genetic control of disease
losses, estimation of heritabilities, and characterization of
breed or strain differences. Numerous examples of this research
exist for leukosis and Marek's disease in poultry (Hutt, 1958;
Freeman and Bumstead, 1987), mastitis and ketosis in cattle (Philipsson
et al., 1980; Solbu, 1982), and parasite infestation and
foot rot in sheep (Albers et al., 1987; Bulgin et al.,
1988). In pigs, breed differences have been reported for atrophic
rhinitis and respiratory diseases (Lundeheim, 1979; Kennedy and
Moxley, 1980). More recently, breed differences for infection
to PRRS has also been reported (Halbur et al., 1998).
Genetic control of certain diseases may be the result of the presence
or absence of receptors that are inherited simply. Resistance
to specific subgroups of leukosis virus in chickens seems to be
inherited simply (Crittenden, 1975) and may be the result of not
having the receptor for the virus. In swine, some individuals
lack the receptor for K88, a cell-surface antigen on some Escherichia
coli, and the E. coli cannot attach to the gut in these
pigs (Gibbons et al., 1977). Resistance to infection from the
K88 strain of E. coli is recessive, but susceptible animals
remain in the population because maternal antibodies allow some
protection. In some breeds, this resistance is not simply recessive
(Michaels et al., 1994) and may result from other loci.
Depending on the species, breeders routinely select animals on
the basis of from one to perhaps as many as 20 traits. This selection
is practiced under environments that challenge livestock greatly
and may increase the incidence of disease if management is poor.
Many researchers have examined approaches to selection for disease
resistance (Gavora and Spencer, 1983; Rothschild, 1985, 1989;
Warner et al., 1987; Straw and Rothschild, 1992). These direct
approaches, with some modifications, are found in Table 1. The
simplest method would be to observe and select breeding stock
for disease resistance under normal production conditions. This
would have no negative effects on production of breeding stock
but probably would not be very informative, because, without disease
(under good hygiene and management), expression of disease resistance
would be questionable. Challenging breeding stock, progeny, or
sibs would be costly, depending on the severity of the disease
challenge, and production could be adversely affected. This method
would be of limited value unless sufficient numbers of progeny
or sibs are tested. Thanks to the new opportunities animal cloning
offers, one alternative possibility to testing progeny or sibs
would be to obtain a large number of clones of embryos from planned
matings of breeding stock. Once raised, one set of these animals
(clones) could be challenged with a specific disease or diseases.
Selection of their clones (other animals) could then occur on
the basis of results from the cloned animals. Because the animals
tested were clones, accuracy would be equal to testing the individuals
|Table 1. Direct approaches to selection for genetic resistance to disease|
Type of selection
|Direct||1. Observe breeding stock|
|2. Challenge breeding stock|
|3. Challenge sibs or|
progeny of breeding stock
|4. Challenge clones|
|Source: Adapted from Gavora and Spencer (1983) and Rothschild (1985).|
Numerous other problems involved with disease challenge or selection under challenging environments exist. These include standardization of the level of challenge exposure to a particular disease and maintenance of isolation facilities for this type of selection. Consider selection under a challenging environment or a disease environment compared with a normal production setting. Although previous research suggests that animals selected under "bad" environments perform as well in "good" environments as those selected directly in "good" environments (Falconer, 1960), if performance rankings of individuals or families seem to be different under the two environments, then genotype by environment interaction probably exists. Estimates of the genetic correlations between disease resistance, immune responsiveness, and production traits under "good" and "bad" environments would be needed to assess the possibility of genetic improvement by this approach. Selection difficulties would arise if there are antagonistic correlations between the disease resistance and production traits. These problems become multiplicative if the number of diseases for which selection is practiced is large. An index approach would be useful, but would require accurate estimates of all the genetic correlations between the disease resistance and performance traits. Such estimates are presently unavailable. Direct selection for disease resistance may also cause a reduction of genetic progress in other traits because of the increased total number of traits.
Given the difficulties in selecting for disease resistance under
challenging environments, alternatives to those methods have been
proposed (Table 2). Immune responsiveness has been suggested
as an indirect indicator of disease resistance (Biozzi et al.,
1980; Gavora and Spencer, 1983; Buschmann et al., 1985; Rothschild,
1989; Warner et al., 1987). Early studies with mice (Biozzi et
al., 1980) have revealed that genetic control of antibody response
to sheep red blood cells was moderately heritable and that selection
for humoral immune response for one antigen may improve humoral
immune response for other antigens. They also investigated genetic
control of cell-mediated responses. Selection for increased humoral
response to sheep red blood cells did not improve cell-mediated
response, suggesting independence of these traits.
|Table 2. Indirect approaches to selection for genetic resistance to disease|
Type of selection
|Indirect||1. Vaccine challenge|
|2. In vitro tests|
|3. Genetic markers|
|Molecular Genetics||Construct resistant genotypes|
|Source: Adapted from Gavora and Spender (1983) and Rothschild (1985).|
In livestock, the most extensive research with genetic control
of immune response has been in poultry (van der Zijpp, 1983a;
Lamont and Dietert, 1990). Genetic control of immune responsiveness
to sheep red blood cells has been thoroughly investigated (Siegal
and Gross, 1980; van der Zijpp and Leenstra, 1980). Heritability
estimates have ranged from 0.28 to 0.38, suggesting that this
trait is under moderate genetic control. Results suggested that
immunization procedures, dosage and site of immunization all affect
measurement and extent of genetic control (van der Zijpp, 1983b).
Such details may make the use of immune response as an indicator
of disease resistance more difficult. Other experiments have
demonstrated that response to vaccination with Newcastle disease,
Salmonella pullorum, and E. coli are under moderate
genetic control and that selection for high and low antibody response
following vaccination is effective (Lamont and Dietert, 1990).
Immune response experiments in swine using sheep red blood cells
and DNP-hapten as antigens have revealed significant between-breed
and within-breed differences (Buschmann et al., 1974; Buschmann,
1980). In a separate series of experiments, the heritability
of secondary immune response and peak response to bovine serum
albumen were estimated to be 0.51 and 0.42, respectively (Huang,
1977). Using commercial vaccines for Bordetella bronchiseptica
and pseudorabies virus, researchers demonstrated significant within-breed
and between-breed differences, low to moderate heritabilities
(0.05 to 0.52) but little or no non-additive (heterosis) genetic
control of immune response (Rothschild et al., 1984a,b; Meeker
et al., 1987a,b). Immune responses to vaccines that contained
two E. coli antigens also were shown to be under moderate
genetic control, with heritability estimates ranging from 0.29
to 0.45 (Edfors-Lilja et al., 1985).
In cattle and sheep, experiments (Lie, 1979; Nguyen, 1984; Muggli
et al., 1987) have revealed genetic variation for immune response
to a variety of antigens, including chicken red blood cells, human
serum albumen, and infectious bovine rhinotracheitis virus (IBRV).
These results suggest that genetic control of immune response
exists for all livestock species.
A second indirect approach would be to consider in vitro
methods as indicators of disease resistance. These methods include,
for instance, phagocytic and bactericidal actions of peripheral
blood monocytes against disease agents such as Salmonella typhimurium
and Staphylococcus aureus (Lacey et al., 1990). Other
such methods include neutrophil metabolic and phagocytic activity
and lymphocyte blastogenesis in response to antigens. Use of
mitogens as an indicator of cell-mediated response has revealed
that genetic differences exist in poultry for the T cell mitogens
phytohaemagglutinin and concanavalin (Lassila et al., 1979).
As with poultry, response to mitogen stimulation has also been
demonstrated in swine for reactivity to phytohaemagglutinin and
poke-week mitogen. Efforts to create an immunocompetence index
in swine have been only moderately successful (Buschmann et al.,
1985). In vitro procedures and their relationship to actual
disease resistance are unknown in general.
A third method would be to locate genetic markers associated with
disease resistance or the actual genes themselves. This approach
was generalized first by those suggesting use of RFLP analyses
in genetic improvement programs (Soller and Beckmann, 1983).
Given the complexity of immune response and its relationship with
disease resistance, the search for marker genes associated with
these traits was enormous, especially in the 1980s when it began.
Modern immunology, however, has revealed that a group of genes,
called the major histocompatibility complex (MHC) genes, seem
to be intimately associated with both disease resistance and immune
responsiveness. All higher life forms are known to possess a
MHC that codes for the predominant cell-surface proteins on cells
and tissues of each individual species. These antigens are markers
of "self" and are unique for animals other than identical
twins or clones. Three classes of protein molecules, class I,
class II and class III, are encoded for by the MHC. The class
I molecules are extremely polymorphic, whereas the class II antigens
are less polymorphic. Class III molecules show only limited polymorphism.
The function of the MHC genes is now generally known. The class
I antigens act as restricting elements in T cell recognition of
virally infected target cells and, thus, are necessary to generate
an immune response. The class II genes (Ir genes) control the
interaction of T cells, B cells, and macrophages in the generation
of the humoral immune response and participate, as well, in aspects
of cellular immunity. The class III genes are intimately involved
with the complement cascade, which ends with the lysis of the
cell or virus particle to which antibody has bound. The structure
and function of the MHC in pigs seems to be similar to that of
humans and mice (Warner et al., 1988; Warner and Rothschild, 1991).
The B complex, the MHC in chickens, has been extensively studied
and shown to be involved with both immune response and disease
resistance. More specifically, the B complex has been shown to
be associated with immune response to synthetic antigens, bovine
serum albumen, Salmonella pullorum bacterium, total IgG
levels, and cell-mediated responses (Nordskog, 1984; Lamont and
Dietert, 1990). Resistance to Marek's disease, Rous Sarcoma virus,
fowl cholera, and lymphoid leukosis viruses has also been demonstrated
to be associated with the chicken MHC (Lamont and Dietert, 1983;
van der Zijpp, 1983a; Lamont, 1989). In retrospect, it seems
that poultry-breeding companies have, in fact, indirectly selected
for certain MHC genotypes by eliminating lines or strains that
were susceptible to certain diseases.
In swine, perhaps the best-studied domestic species, several experiments
have shown that the swine MHC (SLA complex) is associated with
immune response following vaccination. Researchers, working with
miniature inbred pigs and commercial strains, have demonstrated
that the SLA complex is associated with immune response to hen
egg-white lysoyzme and B. bronchiseptica vaccine (Vaiman
et al., 1978b; Rothschild et al., 1984a). The synthetic polypeptide
antigen (T,G)-A-L has been shown to be under the control of the
class II SLA genes in miniature pigs (Lunney et al., 1986). Differences
in quantitative levels of class III molecules have also been shown
to be related to the SLA complex (Vaiman et al., 1978a). Evidence
of SLA association with parasite infection has been reported (Lunney
and Murrell, 1988). A more complete list of disease associations
and the structure and function of the SLA complex has been reviewed
by Warner and Rothschild (1991) and more recently updated by Lunney
and Butler (1998) and Vaiman et al. (1998).
In other livestock species, reports of MHC involvement with immune
response and disease resistance also exist. In cattle, the BoLA
(bovine MHC) complex has been associated with intestinal parasites,
tick susceptibility, and mastitis (Spooner et al., 1988). Bovine
leukemia virus has also been demonstrated to be associated wit
the BoLA complex (Lewin et al., 1988). In the horse, the ELA
(equine MHC) complex seems to be associated with equine sarcoid
tumors (Meredith et al., 1986). Resistance to scrapie (Millot
et al., 1988) was shown to be associated with the sheep
MHC (OLA complex), as was response to vaccination against Trichostrongylus
colubriformis (Outeridge et al., 1985). Opportunities exist
for discovering additional relationships between the MHC and immune
response and disease resistance in livestock. The MHC genes,
therefore, may serve as gene candidates for selection.
More recent molecular genetic approaches have included using gene
maps and quantitative trait loci (QTL) scans to find genes associated
with disease resistance and immune response. To date in pigs,
these QTL scans for disease resistance or immune response QTL
have been very limited. An exception is work underway by Andersson
and colleagues (Edfors-Lilja and Andersson, personal communication)
to study some immune response parameters. Some immune capacity
QTL have been identified including those regions known to control
Ig level and to be associated with immune response to certain
vaccines. Also, a QTL for base cortisol level which may be related
to stress and perhaps immune response, has been mapped to the
end of chromosome 7 (Milan et al., 1998).
Analyses of associations of candidate genes have been more substantial.
The general location of the K88 E. coli receptor has been
known for some time, and fine mapping and candidate gene analysis
of the region is underway in many labs. It is hoped that the
actual gene controlling this trait will be found soon. Two alpha
(1,2) fucosyltransferase genes (FUT1, FUT2) on porcine chromosome
6q11 have been identified and are closely linked to the blood
group inhibitor (S) and Escherichia coli F18 receptor (ECF18R)
loci. Vögeli and colleagues (Meijerink
et al., 1997) found a polymorphism which is closely linked
to ECF18R in Large White, Landrace, Hampshire, Duroc, and Pietrain
pigs, and it now is clear that FUT1 and FUT2 loci are associated
with E. coli F18 adhesion resistant animals in these breeds.
Further research to confirm that the FUT1 or FUT2 gene products
are involved in the synthesis of carbohydrate structures responsible
for bacterial adhesion remains to be determined. The gene for
Natural Resistance Associated Macrophage Protein 1 (NRAMP1), associated
with resistance to Salmonella challenge in mice, has been recently
mapped to pig chromosome 15 (Sun et al., 1998). Additional studies
of the role of NRAMP1 are presently underway. Several other candidate
genes are being investigated, including those controlling immunoglobulin
and interleukin production. Genes associated with human disorders,
which have been identified and mapped in the pig, include clotting
factor IX (Signer et al., 1996) and the familial hypercholesterolaemia
gene (Hasler-Rapacz et al., 1996).
When one considers the problems of selection under challenging
environments, the possibilities to make improvements in disease
resistance and immune responsiveness seem limited. First, direct
selection for disease resistance may be too costly. Second, results
in a number of species suggest that humoral immune response to
one antigen is not necessarily a good indicator of humoral response
to other antigens or to other aspects of the immune response.
Third, MHC genotypes known to be associated with susceptibility
to one disease differ from those known to be associated with susceptibility
to different diseases. The heterozygosity of genes that influence
immune response, especially those of the MHC, is an obvious advantage,
and polymorphism for MHC loci would allow species the opportunities
to survive a variety of disease challenges. The interrelationships
among disease resistance and immune responsiveness must also take
into account their association with production traits. It might
seem reasonable to believe that selection for improved production
efficiency might also have indirectly selected for improved disease
resistance and immune responsiveness. Given the use of medication
and the frequent vaccination programs that exist in livestock
production, it seems that these husbandry practices may have masked
genetic resistance to disease.
Experimental evidence of the relationships of disease resistance,
immune response and production traits is scarce. In poultry,
results are contradictory (van der Zijpp, 1983b; Lamont, 1989).
In one experiment, selection for rapid growth rate was associated
with increased susceptibility to Marek's disease. In another
set of experiments, associations with Marek's disease and egg
laying performance were contradictory. Immune response to sheep
red blood cell seems to be antagonistically associated with growth
rate in broilers. Immune response to Newcastle disease vaccine
seems to be negatively correlated with hatchability in Japanese
quail and with egg production in chickens.
In other livestock species the results are similar. Meeker et
al. (1987a) found that growth rate was negatively correlated
with immune response following vaccination with either a commercially
prepared B. bronchispetica or pseudorabies virus vaccine
but that backfat at market weight was not correlated with either
immune response. Pigs that have the intestinal receptor for K88
E. coli (and are therefore susceptible) grew faster and
had better feed conversion (Edfors-Lilja et al., 1986). Results
with cattle suggest that immune response to IBRV vaccination was
not associated with performance.
A final point to consider is that the MHC has been linked to a
number of production traits in the pig (as reviewed in numerous
articles in Warner et al., 1988; Warner and Rothschild, 1991;
Lunney and Butler, 1998). These reports include associations
of growth, backfat, and reproduction traits with the pig MHC.
It seems reasonable to assume that, inasmuch as immune responsiveness
and production traits both seem to be associated with the MHC,
these genes should then be the ones to exploit in future selection
programs. In addition, the interluekin genes may play a similar
Future Directions and Opportunities
A number of limitations seem to exist that may impede progress
towards breeding livestock, by conventional methods, that are
more disease resistant and have improved immune responsiveness.
The first of these is that limited funds are now committed to
disease testing of different germplasm. This lack of funds has
limited the development of our understanding of the extent of
genetic resistance to disease. In addition, the general lack
of associations among immune-response parameters and the negative
correlations of some diseases and immune response with production
traits make conventional selection methods extremely difficult.
The alternative approach would be to identify individual marker
loci or the actual genes that are associated with disease resistance
and improved immune response. The MHC genes seem to be likely
candidates because they are already known to be associated with
these traits. Once specific MHC alleles and other genes such
as NRAMP1 can be identified, they can be used in marker-assisted
selection or transferred to create transgenic animals with improved
disease resistance and immune responsiveness. The payoff for
such research is likely to be extremely large. For livestock
producers, the benefits of genetically engineered animals would
most likely include increased protection from disease and improved
production performance under challenging environments. In the
end, the consumer also would benefit from these developments,
which could greatly alter livestock production.
This article is Journal Paper No. J-18175 of the Iowa Agriculture
and Home Economics Experiment Station, Ames, Project 3215.
Albers, G.A., Gray, G.D., Piper, L.R., Barker, J.S.F.,
Le Jambre, L.F., and Barger, I.A. 1987. The genetics of resistance
and resilience to Hamemonchus contortus infection in young
Merino sheep. International Journal of Parasitology 17:1355-63.
Biozzi, G., Siqueira, M., Stiffel, C., Ibanex, O.M.,
Mouton, D., and Ferreira, V.C.A. 1980. Genetic selection for
relevant immunological functions. In: Progress in Immunology
IV. Academic Press, New York, pp. 432-57.
Bulgin, M.S., Lincoln, S.D., Parker, C.F., Sowth, P.J., Dahmen, J.J., and Lane, V.M. 1988. Genetic-associated resistance to foot rot in selected Targhee sheep. Journal of the American Veterinary Medicine Association 192:512-15.
Buschmann, H. 1980. A selection experiment on the
antibody forming capacity to DNP-hapten in pigs. Animal Blood
Groups and Biochemical Genetics II (Suppl. 1), 4.
Buschmann, H., Junge, V., Krausslich, H., and Radizikowski,
A. 1974. A study of the immune response to sheep erythrocytes
in several breeds of swine. Medical Microbiology and Immunology
Buschmann, H., Krausslich, H., Herrmann, H., Meyer,
J., and Kleinschmidt, A. 1985. Quantitative immunological parameters
in pigs - experience with the evaluation of an immunocompetence
profile. Zeitschrift Fur Tierzuchtung Zuchtungsbiologie
Crittenden, L.B. 1975. Two levels of genetic resistance
to Marek's disease. Avian Disease 19:281-92.
Edfors-Lilja, I., Gahne, B., and Petersson, H. 1985.
Genetic influence on antibody response to two Escherichia
coli antigens in pigs. II. Difference in response between
paternal half sibs. Zeitschrift Fur Tierzuchtung Zuchtungsbiologie
Edfors-Lilja, I., Peterson, H., and Gahne, B. 1986.
Performance of pigs with and without the intestinal receptor
for Escherichia coli K88. Animal Production 42:381-8.
Falconer, D.S. 1960. Selection of mice for growth
on high and low planes of nutrition. Genetic Research
Freeman, B.M., and Bumstead, N. 1987. Breeding
for disease resistance - the prospective role of genetic manipulation.
Avian Pathology 16:353-65.
Gavora, J.S., and Spencer, J.L. 1983. Breeding
for immune responsiveness and disease resistance. Animal Blood
Groups and Biochemical Genetics 14:159-80.
Gibbons, R. A., Selwood, R., Burrows, M., and Hunter,
P.A. 1977. Inheritance of resistance to neonatal Escherichia
diarrhea in the pig: Examination of the genetic system. Theoretical
and Applied Genetics 55:65-70.
Halbur, P. G., Rothschild, M.F., Paul, P.S., Thacker,
B.J., and Meng, X.J. 1998. Differences in susceptibility of
Duroc, Hampshire, and Meishan pigs to infection with a high virulence
strain (VR2385) of porcine reproductive and respiratory syndrome
virus (PRRSV). Journal of Animal Breeding and Genetics
Hasler-Rapacz, J., Ellegren, H., Andersson, L., Kirkpatrick,
B.W., Kirk, S., Fridolfsson, A.K., and Rapacz J. 1996. Mapping
of a major locus for familial hypercholesterolaemia to porcine
chromosome 2 and identification of a candidate gene; the low-density
lipoprotein receptor. Animal Genetics 27 (Suppl. 2):113.
Huang, J. 1977. Quantitative Inheritance of
Immunological Response in Swine. Unpublished PhD dissertation.
University of Hawaii, Honolulu, Hawaii.
Hutt, F.B. 1958. Genetic Resistance to Disease in Domestic Animals. Comstock, Ithaca, NY.
Kennedy, B.W., and Moxley, J.E. 1980. Genetic factors
influencing atrophic rhinitis in the pig. Animal Production
Lacey, C., Wilkie, B.N., Kennedy, B.W., and Mallard,
B.A. 1990. Genetic and other effects on bacterial phagocytosis
and killing by cultured peripheral blood monocytes of SLA-defined
miniature pigs. Animal Genetics 20:371-82.
Lamont, S.J. 1989. The chicken major histocompatibility
complex in disease resistance and poultry breeding. Journal
of Dairy Science 72:1328-33.
Lamont, S.J., and Dietert, R.R. 1990. Immunogenetics.
In: Crawford, R. D. (Ed.), Poultry Breeding and Genetics.
Lassila, O., Nurmi, T., and Eskola, J. 1979. Genetic
differences in the mitogenic response of peripheral blood lymphocytes
in the chicken. Journal of Immunogenetics 6:37-43.
Lewin, H.A., Wu, M.-C., Stewart, J.A., and Nolan,
T.J. 1988. Association between BoLA and subclinical bovine leukemia
virus infection in a herd of Holstein-Friesian cows. Immunogenetics
Lie, O. 1979. Genetic analysis of some immunological
traits in young bulls. Acta Veterinaria Scandinavica 20:372-86.
Lundeheim, N. 1979. Genetic analysis of respiratory
diseases of pigs. Acta Agriculturae Scandinavica 29:209-5.
Lunney, J., and Butler, J. 1988. Immunogenetics.
In: Rothschild, M.F., and Ruvinsky, A. (Eds.). Genetics of
the Pig. CAB Press, pp 163-198.
Lunney, J., and Murrell, K.D. 1988. Immunogenetic
analysis of Trichinella spiralis infections in swine.
Veterinary Parasitology 29:179-93.
Lunney, J.K., Pescovitz, M.D., and Sachs, D.H. 1986.
The swine major histocompatibility complex: its structure and
function. In: Tumbleson, M.E. (ed.), Swine in Biomedical Research.
Plenum, New York, vol. 3, pp 1821-36.
Meeker, D.L., Rothschild, M.F., Christian, L.L.,
Warner, C.M., and Hill, H.T. 1987a. Genetic control of immune
response to pseudorabies and atrophic rhinitis vaccines. I. Heterosis,
general combining ability and relationship to growth and backfat.
Journal of Animal Science 64:407-13.
Meeker, D.L., Rothschild, M.F., Christian, L.L.,
Warner, C.M., and Hill, H.T. 1987b. Genetic control of immune
response to pseudorabies and atrophic rhinitis vaccines. II. Comparison
of additive direct and maternal genetic effects. Journal of
Animal Science 64:414-119.
Meijerink, E., Fries, R., Vogeli, P.,
Masabanda, J., Wigger, G., Stricker, C., Neuenschwander, S., Bertschinger,
H.U., and Stranzinger, G. 1997. Two alpha(1,2) fucosyltransferase
genes on porcine Chromosome 6q11 are closely linked to the blood
group inhibitor (S) and Escherichia coli F18 receptor (ECF18R)
loci. Mammalian Genome 8:736-741.
Meredith, D., Elser, A.H., Wolf, B., Soma, L.R.,
Donawick, W.J., and Lazary, S. 1986. Equine leukocyte antigens:
relationships with sarcoid tumors and laminitis in two pure breeds.
Michaels, R.D., Whipp, S.C., and Rothschild, M.F.
1994. Resistance of Chinese Meishan, Fengjing and Minzhu pigs
to K88ac+ Escherichia coli. American Journal of Veterinary
Milan, D., Bidanel, J.P., Le Roy, P., Chevalet, C.,
Woloszyn, N., Caritez, J.C., Gruand, J., Bonneau, M., Lafaucheur,
L., Renard, C., Vaiman, M., Mormède, P., Désautés,
C., Gellin, J., and Ollivier, L. 1998. Current status of QTL
detection in Large White x Meishan crosses in France. Proc
6th World Congress Quantitative Genetics of Livestock
Millot, P., Chatelain, J., Dautheville, C., Salmon,
D., and Cathala, F. 1988. Sheep major histocompatibility (OLA)
complex: linkage between a scrapie susceptibility/resistance locus
and the OLA complex in the Ile-de-France sheep progenies. Immunogenetics
Muggli, N.E., Hohenboken, W.D., Cundiff, L.V., and
Mattson, D.E. 1987. Inheritance and interaction of immune traits
in beef calves. Journal of Animal Science 64:385-93.
Nguyen, T.C. 1984. The immune response in sheep.
Analysis of age, sex and genetic effects on the quantitative
antibody response to chicken red blood cells. Veterinary Immunology
and Immunopathology 5:237-45.
Nordskog, A.W. 1984. Selection for immune response
as related to the major histocompatibility complex (MHC). Annales
Agriculturae Fenniae 23:255-9.
Outeridge, P.M., Windon, R.G., and Dinien, J.K.
1985. An association between a lymphocyte antigen in sheep and
the response to vaccination against the parasite Trichostrongylus
colubriformis. International Journal of Parasitology
Philipsson, J., Thafvelin, G., and HedebroVelander,
I. 1980. Genetic studies on disease recordings in first lactation
cows of Swedish dairy breeds. Acta Agriculturae Scandinavica
Rothschild, M.F. 1985. Selection for disease resistance
in the pig. Pig News and Information 6:277-80.
Rothschild, M.F. 1989. Selective breeding for immune
responsiveness and disease resistance in livestock. AgBiotech
News and Information 3:355-60.
Rothschild, M.F., Chen, H.L., Christian, L.L., Lie,
W.R., Venier, L., Cooper, M., Briggs, C., and Warner, C.M. 1984a.
Breed and swine lymphocyte antigen haplotype differences in agglutination
titers following vaccination with B. bronchiseptica. Journal
of Animal Science 59:643-9.
Rothschild, M.F., Hill, H.T., Christian, L.L., and
Warner, C.M. 1984b. Genetic differences in serum neutralization
titers of pigs following vaccination with pseudorabies modified
live virus. American Journal of Veterinary Research 45:1216-18.
Siegal, P.B., and Gross, E.B. 1980. Production
and persistence of antibodies in chickens to sheep red erythrocytes.
1. Directional selection. Poultry Science 59:1-5.
Signer, E.N., Armour, J.A.L., and Jeffreys, A.J.
1996. Detection of an MboI RFLP at the porcine clotting factor
IX locus and verification of sex linkage. Animal Genetics
Solbu, H. 1982. Heritability estimates and progeny
testing for mastitis, ketosis and "all diseases". Zeitschrift
Fur Tierzuchtung Zuchtungsbiologie 101:210-19.
Soller, M., and Beckmann, J.S. 1983. Genetic polymorphism
in varietal identification and genetic improvement. Theoretical
and Applied Genetics 67:25-33.
Spooner, R.L., Brown, P., Glass, E.J., Innes, E.A.,
and Williams, J.L. 1988. Characterization and function of the
bovine MHC. In: Warner, C.M., Rothschild, M.F., and Lamont, S.J.
(Eds.), The Molecular Biology of the Major Histocompatibility
Complex of Domestic Animal Species. Iowa State University
Press, Ames, pp. 79-96.
Straw, B.E., and M.F. Rothschild. 1992. Genetic
influences on liability to acquired disease. In: Diseases
of Swine. 7th ed., ISU Press. pp. 709-717.
Sun, H. S., Wang, L., Rothschild, M.F., and Tuggle,
C.K. 1998. Mapping of the natural-resistance associated macrophage
protein (NRAMP1) gene in pigs. Animal Genetics 29:138-140.
Vaiman, M., Hauptman, G., and Mayer, S. 1978a.
Influence of the major histocompatibility complex in the pig (SLA)
on haemolytic complement levels. Journal of Immunogenetics
Vaiman, M., Metzger, J.J., Renard, Ch., and Vila,
J.P. 1987b. Immune response gene(s) controlling the humoral
anti-lysozyme response (Ir-Lys) linked to the major histocompatibility
complex SL-A in the pig. Immunogenetics 7:231-8.
Vaiman, M., Chardon, P., and Rothschild, M.F. 1998.
Porcine major histocompatibility complex. Office of International
Des Epezooties (OIE) Review 17: 95-107.
van der Zijpp, A.J. 1983a. Breeding for immune
responsiveness and disease resistance. World's Poultry Science
van der Zijpp, A.J. 1983b. The effect of the genetic
origin, source of antigen, and dose of antigen in the immune response
of cockerels. Poultry Science 62:205-11.
van der Zijpp, A.J., and Leenstra, F.R. 1980. Genetic
analysis of the humoral immune response of white leghorn chicks.
Poultry Science 59:1363-9.
Warner, C.M., Meeker, D.L., and Rothschild, M.F.
1987. Genetic control of immune responsiveness: A review of
its use as a tool for selection for disease resistance. Journal
of Animal Science 64:159-80.
Warner, C.M., and Rothschild, M.F. 1991. The swine
major histocompatibility complex (SLA). In: Srivastava, R. (ed.)
Immunogenetics of the MHC, pp 368-398.
Warner, C.M., Rothschild, M.F., and Lamont, S.J.
1988. The Molecular Biology of The Major Histocompatibility
Complex of Domestic Animal Species. Iowa State University
Press. Ames, 193 pp.