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The Journal of Immunology, 1998, 161: 829-835.
Copyright © 1998 by The American Association of Immunologists

Mapping Quantitative Trait Loci for Immune Capacity in the Pig1

Inger Edfors-Lilja2,*,{dagger}, Eva Wattrang3,{ddagger}, Lena Marklund{dagger}, Maria Moller{dagger}, Lena Andersson-Eklund{dagger}, Leif Andersson{dagger} and Caroline Fossum{ddagger}

* Department of Engineering and Natural Sciences, University of Växjö, Växjö, Sweden; {dagger} Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden; and {ddagger} Department of Veterinary Microbiology, Division of Immunology, Swedish University of Agricultural Sciences, Uppsala, Sweden


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Immune capacity traits show considerable genetic variation in outbred populations. To identify quantitative trait loci (QTLs) for immune capacity in the pig, various measures of immune function (total and differential leukocyte counts, neutrophil phagocytosis, mitogen-induced proliferation, IL-2 production, and virus induced IFN-{alpha} production in whole blood cultures, and Ab responses to two Escherichia coli antigens) were determined in 200 F2 animals from a wild pig–Swedish Yorkshire intercross. The pedigree has been typed for 236 genetic markers covering all autosomes, the X chromosome and the X/Y pseudoautosomal region. Through interval mapping using a least-squares method, four QTLs with significant effects were identified; one for total leukocyte counts, one for mitogen-induced proliferation, one for prevaccination levels of Abs to E. coli Ag K88, and one for Ab response to the O149 Ag. In addition, several putative QTLs were indicated. The results from the present study conclusively show that it is possible to identify QTLs for immune capacity traits in outbred pig populations by genome analysis.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The pig serves as a large animal model for several human diseases (1, 2, 3) and may be used in the future for xenotransplantation (4). Increased disease resistance through improved general immune capacity would also prove beneficial for the welfare and productivity of farm animals. Thus, the porcine immune system is the subject of growing interest both in basic and applied research. Consequently, the elaboration and standardization of reagents for studies of immune functions in the pig has emerged rapidly during recent years (5). However, a comprehensive elucidation of the basis for variation in immune functions also requires further knowledge of their genetic regulation.

Several studies have shown that genetic polymorphism within the MHC influences variation in immune functions and/or disease resistance (6). However, non-MHC genes also regulate immune responsiveness, and a polygenic control of quantitative immune response traits has been confirmed in several experimental studies (7). In the pig, additive genetic variation has been documented for a number of immune traits, e.g., Ab response (8, 9, 10, 11, 12), proliferative and cytokine responses of mononuclear cells (12, 13, 14, 15, 16), delayed-type hypersensitivity reactions (14), and total and differential leukocyte counts (16). Medium high to high heritabilities (h2 = 0.3–0.8) have been estimated for several of the immune traits suggesting a large genetic impact.

Linkage mapping using dense genetic maps is a straightforward approach to locate genes that control traits and inherited diseases with a monogenic inheritance. The same approach has also successfully been used to identify quantitative trait loci (QTLs)4 that control various polygenic traits in different organisms (17, 18, 19, 20, 21, 22, 23). Regarding immune functions, several QTLs influencing Ab response have recently been identified in mice (24, 25). Detailed linkage maps of the porcine genome are now available (26, 27, 28). In Sweden, a reference pedigree, created by intercrossing the European wild pig with Swedish (Sw) Yorkshire pigs, was initiated in 1988 as a part of a Nordic project on animal gene mapping (19, 29, 30). The pedigree has up to now been typed for more than 200 genetic markers (28), and QTLs for production traits such as growth and fat deposition have been identified (19, 30).

We here report on the identification of QTLs for immune capacity in the pig. Several measures of immune function (i.e., total and differential leukocyte counts, neutrophil phagocytosis, mitogen-induced proliferation and IL-2 production, virus-induced IFN-{alpha} production of mononuclear cells, and Ab responses to Escherichia coli Ags) were determined for the F2 animals in the pedigree. Through interval mapping using a least-squares method, we identified four QTLs with significant effects on some of these immune traits, all located on different chromosomes.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Animals and experimental design

The animals originated from a reference pedigree developed for gene mapping by crossing two European wild pig boars with eight Sw Yorkshire sows (19, 29). Four of the F1 boars were subsequently mated to 22 F1 sows generating 44 litters, from which a total of 200 F2 animals were included in the present study. The eight parental sows had earlier been included as dams in a study in which heritabilities were estimated for some of the immune parameters (16). All animals were housed under conventional conditions. The male piglets were castrated at 2 wk of age, and all pigs were weaned at 7 wk of age by removing the sow from the farrowing pen. The weaned piglets were raised litterwise until approximately 3 mo old when they were allocated to a finishing unit where they were housed in groups (n = 40) of five nonlittermates. Immediately before allocation, blood samples were collected from the cranial vena cava by using evacuated glass tubes (B-D Vacutainer, Maylan, France) without additive and with 15 mg EDTA K3 or 143 U heparin as additives. In addition, serum samples were collected 2 and 5 wk after allocation for antibody determination. Serum and EDTA blood samples for DNA analyses were stored at -70°C.

Several growth and carcass traits were recorded during the rearing period and at slaughter of the pigs (19, 30). Intestinal specimens were collected after slaughter, and all animals were typed for the presence of the intestinal receptor for E. coli K88ab, K88ac (31).

Genetic markers

The pedigree has been typed for 236 genetic markers, including blood group loci, protein markers, RFLPs, and microsatellites (28). The established linkage map, which covers nearly all parts of the pig genome, has a total sex-average map-length of 2300 centiMorgans (cM). Linkage groups have been assigned to all 18 autosomes, the X chromosome and the X/Y pseudoautosomal region.

Total and differential white blood cell counts

The total number of white blood cells (WBC) was determined in a celloscope, and differential WBC counts were carried out by using blood smears stained with Giemsa’s and May Grünewald’s solutions. The analyses were performed at the Department of Clinical Chemistry, Swedish University of Agricultural Sciences. From these data the total numbers of polymorphonuclear leukocytes (PMNL), band neutrophils, segmented neutrophils, eosinophils, and lymphocytes per liter blood were calculated.

Phagocytic capacity of blood PMNL

The phagocytic capacity of blood PMNL was determined in whole blood by a luminol enhanced chemiluminiscence (CL) assay as earlier described (16, 32). The phagocytosis was induced with opsonized zymosan particles, and the peak CL value was chosen as a measure of the phagocytic capacity.

Mitogen-induced proliferation and IL-2 production

The mitogen-induced proliferation was determined in whole blood cultures incubated as previously described (33). Cultures were stimulated with Con A (5 µg/ml; Pharmacia, Uppsala, Sweden), PHA (1 µg/ml; Wellcome, Dartford, U.K.), and PWM (10 µg/ml; Boehringer Mannheim, Mannheim, Germany), respectively, or grown in plain growth medium for 72 h, the last 24 h in the presence of 0.5 µCi [3H]thymidine (specific activity, 5 Ci per mmol; Amersham International, Amersham, U.K.). The proliferation was expressed as mean cpm values of triplicate wells.

The levels of IL-2 activity were determined in supernatants collected from the cultures above after 48 h of incubation. A bioassay measuring the proliferation of an IL-2-dependent cytotoxic T lymphocyte line was used (15), and the IL-2 activity was expressed as percentage of a laboratory standard included at every test occasion.

Aujeszky’s disease virus (ADV)-induced IFN-{alpha} production

The IFN-{alpha} production of PBMC was induced with ADV (34) and adapted to cultures of whole blood (33). In brief, 200 µl of heparinized blood was diluted 1:10 in growth medium and incubated on monolayers of fixed, ADV (Phylaxia strain)-infected porcine kidney cells (PK-15; Flow Laboratories, Irvine, Scotland, U.K.) in flat-bottomed microtiter plates. After 18 h at 37°C, the culture supernatants were collected and the IFN-{alpha} content was measured by a sensitive immunoassay for porcine IFN-{alpha} (35).

Immunization procedure and detection of serum antibodies to E. coli Ags

The F2 animals were immunized intramuscularly with an E. coli vaccine (Porcovac, Hoechst, Germany), containing the K88ab, K88ac, and O149 Ags (31). One animal per pen (n = 40) was used as a nonvaccinated control. Blood samples were collected immediately before immunization and 3 wk later. Serum IgG Abs to the K88ab, K88ac, and O149 Ags, respectively, were determined by ELISA (EC Diagnostics, Uppsala, Sweden), and the antibody levels are expressed as optical density values at a wave length of 492 nm, OD492 values.

Statistical analysis

An analytical method based on least-squares for the identification of QTLs segregating in crosses between outbred lines (36, 37) was used. In this analysis, the probabilities for every individual being each of the three genotypes (homozygous for alleles from the wild pig or from the Sw Yorkshire, or inheriting one allele from each breed) were estimated by using marker information for a putative QTL in a given position in the linkage group. The phenotypic score (i.e., an immune capacity trait) of an individual was regressed onto the additive and dominance coefficients of the QTL calculated from these genotype probabilities. The additive effects were estimated as half of the deviation of animals homozygous for the wild pig alleles from those homozygous for the Sw Yorkshire alleles, and the dominance effects as the deviation of heterozygous animals from the mean of the two homozygotes. The F-ratio values obtained by repeating the procedure at 1-cM intervals were plotted against the chromosomal position, with the highest point of the curve representing the most likely position of a QTL. The significance levels used are the significance thresholds obtained by permutation tests (38) for the immune traits. Covariates and fixed effects (i.e., family, sex, live weight, age) were analyzed using the GLM procedure of SAS (39) and included in the QTL analysis when appropriate.

The difference between the parental populations was also tested by calculating the average proportion of wild pig genome (i.e., the average additive and dominance coefficients from the QTL analysis) of each F2 animal. This parameter was then used as covariate in an analysis of covariance, and the difference between wild pig and Sw Yorkshire was estimated as twice the additive effect.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
The results of the QTL analyses are compiled in Tables I and II, and the chromosomal location of QTLs are depicted in Figure 1Go. All suggested QTLs with a genome-wide F-value >= 6.0 are included. The F-values corresponding to suggestive significance thresholds, i.e., one false significant result per genome analysis (p ~ 0.05 for each of the 18 autosomes), were between 4.3 and 5.9 for the individual chromosomes. It is likely that several of the suggested QTLs represent type I errors, but they are included to facilitate comparisons with results of future studies and to reduce the risk that true QTLs which did not reach the genome-wide 5% significance threshold in the present study are ignored.



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  		FIGURE 1. Location of QTLs for various immune capacity traits in the pig. Only QTLs with test statistics F >= 6.0 are given. The linkage map is based on sex-average distances and given as Kosambi cM (28 ).

 
Total leukocyte counts

The total number of blood leukocytes (23.0 ± 6.4 x 109/L, mean value ± SD, n = 199) in the F2 wild pig x Sw Yorkshire intercrosses was slightly higher than previously reported for purebred Sw Yorkshire pigs (20.6 ± 4.4 x 109/L blood, n = 124 (16)). The analysis of this parameter revealed one significant QTL located 78 cM from the proximal end of chromosome 1 (Table IGo; Figs. 1Go and 2Go). Only the additive effect was significant, and the wild pig allele at this QTL was associated with a higher number of leukocytes (Table IGo), the difference between the two homozygotes being 6.3 x 109 leukocytes per liter blood.


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  		Table I. Location and estimated effects of putative QTLs (mean ± SE) affecting leukocyte counts, proliferation, and IL-2 activity segregating in a wild pig x Sw Yorkshire intercross

 


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  		FIGURE 2. Test statistic curve for the possible presence of QTLs affecting the total number of WBC at chromosome 1. The graphs plot the F ratio testing the hypothesis of a single QTL in a given position on the chromosome. The significance level for p = 0.05 is given. The map of chromosome 1 is shown with map distances in Kosambi cM (28 ).

 
Differential leukocyte counts

Differential leukocyte counts revealed that the circulating leukocytes were equally distributed into PMNL (46.1 ± 12.2%) and lymphocytes (47.0 ± 12.1%). The total number of PMNL (10.8 ± 5.0 x 109/L blood, n = 199) was somewhat higher for the wild pig intercrosses than for purebred Sw Yorkshire pigs (8.7 ± 2.9 x 109/L blood, n = 124 (16)). For both PMNL and lymphocytes, QTLs were indicated in the same region of chromosome 1 as for total numbers of WBC (F = 5.7 and 4.8, respectively, p > 0.2). The PMNL were further subdivided into segmented neutrophils (10.5 ± 4.8 x 109/L blood), band-formed neutrophils (0.3 ± 0.7 x 109/L blood), eosinophils (0.8 ± 0.8 x 109/L blood), and basophils (0.09 ± 0.17 x 109/L blood), respectively. No significant QTL was found for differential cell counts, but several putative (0.05 < p <= 0.20) QTLs were indicated (Table IGo and Fig. 1Go).

Proliferation and IL-2 production

A large inter-individual variation was found for the spontaneous and mitogen-induced proliferation and IL-2 production. As regards proliferation (spontaneous, 3,010 ± 3,450 cpm; PHA induced, 22,200 ± 13,900 cpm; PWM induced, 28,600 ± 10,800 cpm; Con A induced, 52,500 ± 22,300 cpm; n = 199), the coefficient of variation was similar to that previously recorded for purebred Sw Yorkshire pigs. In contrast, the coefficient of variation for the IL-2 production in these cultures (spontaneous, 16.2 ± 17%; PHA induced, 27.9 ± 30.7%; PWM induced, 186.8 ± 110.3%; Con A induced, 54.8 ± 57.9%; n = 199) was higher than that for purebred pigs (16). Because the previous study was carried out with purified PBMC and the present analyses were performed using whole blood cultures, a comparison of the absolute values is not valid.

For the mitogen-induced proliferation, the highest F value (8.6) was found for a QTL on chromosome 4 with effect on the PWM-induced proliferation (Table IGo). Animals carrying wild pig alleles at this QTL showed a lower PWM-induced proliferation, with an additive gene effect corresponding to a difference between the homozygotes of 8890 cpm.

As regards mitogen-induced IL-2 production, the wild pig alleles were on average associated with a higher PHA-induced IL-2 activity when this trait was regressed on the average proportion of wild pig genome (p < 0.01). However, no individual QTL affecting IL-2 production reached the genome-wide significance threshold (Table IGo).

Phagocytic capacity and ADV-induced IFN-{alpha} production

The phagocytic capacity in whole blood, expressed as peak CL per PMNL, was 3.3 ± 1.8 mV per 106 cells (mean value ± SD, n = 167). The coefficient of variation was similar to that previously recorded for purebred Sw Yorkshire (6.3 ± 3.4 mV per 106 cells, n = 72 (16)). The IFN-{alpha} production showed a pronounced phenotypic variation (26.8 ± 41.8 U IFN-{alpha} per ml, n = 179). Similarly, a large inter-individual variation was previously found for this trait using purified PBMC of purebred Sw Yorkshire pigs (122.8 ± 212.9 U IFN-{alpha} per ml, n = 124 (16)). No QTL influencing the phagocytic capacity was identified. Neither was any QTL found for the ADV-induced IFN-{alpha} production in whole blood cultures, although a higher production was indicated (p < 0.05) for wild pigs when the effect of the average proportion of wild pig genome was tested.

Specific IgG levels to E. coli Ags

The E. coli immunization provoked a significant (p <= 0.001) increase in Ab levels to the E. coli Ags tested, from an OD492 value of 0.33 ± 0.01 to 0.64 ± 0.02 for K88 and from 0.37 ± 0.01 to 0.61 ± 0.01 for O149, respectively (least-square means ± SE). The nonvaccinated control animals (n = 40) remained at prevaccination levels (OD492 value, 0.36 ± 0.04 and 0.38 ± 0.04 for IgG levels to K88 and O149, respectively).

A QTL with significant effect on the specific Ab response to O149 was found approximately 68 cM from the proximal end of chromosome 6 (Table IIGo and Fig. 1Go). The wild pig alleles were associated with higher IgG response to the O149 Ag, the additive gene effect leading to a difference in Ab response (day 21-0) between the homozygotes of 0.22 (OD492 value). Also, prevaccination IgG levels differed between pigs carrying wild or Yorkshire alleles. A significant QTL for prevaccination levels of IgG to the Ag K88 was found on chromosome 5 with the Sw Yorkshire alleles associated with higher titers. Additional putative QTLs influencing IgG levels to the E. coli Ags before and after immunization were also identified (Table IIGo and Fig. 1Go).


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  		Table II. Location and estimated effects of putative QTLs (mean ± SE) affecting IgG titers to the E. coli Ags O149 and K88 segregating in a wild pig x Sw Yorkshire intercross

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The present results clearly show that a number of loci contribute to the variation in some immune capacity traits in the pig. In total, four QTLs reached the genome-wide significance threshold (one for total leukocyte counts, one for mitogen-induced proliferation, one for prevaccination Ab levels to the E. coli Ag K88, and one for the Ab response to the O149 Ag), and several putative QTLs approaching significance were indicated. It should be noted that with the limited numbers of F2 animals available in the present study, it is only possible to identify QTLs with large effects. The four significant QTLs identified are clearly more than expected by chance because we have used a genome-wide significance threshold of 5% and analyzed 19 traits.

A QTL with a large effect on the total number of WBC was identified on chromosome 1, and a number of other QTLs influencing specific leukocyte populations were indicated. Earlier studies have shown that the levels of circulating neutrophilic granulocytes are under genetic control in humans (40, 41, 42), cattle (43), rats (44), and mice (45). For purebred Sw Yorkshire pigs a high heritability (h2 = 0.87 ± 0.41) has been suggested for the total number of circulating neutrophilic granulocytes along with a medium high heritability estimate for the total number of WBC (16). In concordance with these heritability estimates from purebred Yorkshire pigs, the total WBC numbers were found to vary between animals carrying different Yorkshire alleles at the QTL on chromosome 1. Moreover, the present results support earlier findings suggesting that several loci are involved in the regulation of blood leukocyte levels (44, 45). The present material did not allow identification of the actual gene(s) involved in the regulation of leukocyte numbers, but those regulating leukopoiesis and/or the release of leukocytes into the circulation will be likely candidates.

The genetic variation earlier documented for mitogen-induced proliferation and IL-2 activity in the pig (12, 13, 14, 15, 16) was confirmed as several putative QTLs were found for these traits; for mitogen-induced proliferation on chromosomes 4, 6, and 7, and for IL-2 production on chromosomes 7 and 12. In addition, a QTL for spontaneous proliferation was indicated on chromosome 13. A chromosomal region harboring genes that control the maintenance of IL-12 responsiveness and thus induce Th1 cell development was recently identified on murine chromosome 11 (46). Several genes with potential influence on T cell differentiation are located within this region, including IL-4, IL-5, IL-3, and IFN regulatory factor. A region syntenic with this part of murine chromosome 11 has been localized to human chromosome 5q31:1, which in turn corresponds to pig chromosomes 2q21-qter or 16 (47). No effect of these chromosomal regions was however detected in the present study.

Up to a 100-fold variation in IFN-{alpha} production between individuals has been reported in both mice and humans (48). In mice, this variation is controlled by a number of nonstructural If genes that influence the amount of IFN yield per cell. The murine If-1 locus, located on chromosome 3, affects the Newcastle disease virus-induced expression of IFN-{alpha}, TNF-{alpha}, and IL-6 genes (49). Also in pigs, a large phenotypic variation in levels of virus-induced IFN-{alpha} has been found (16) in addition to breed differences in IFN-{alpha} yield per cell (50). In spite of that, a very low heritability was found for the ADV-induced production of IFN-{alpha} among purebred Sw Yorkshire pigs, and no QTL was found for this trait in the present study. However, the large variation in IFN-{alpha} production found among the Sw Yorkshire population implies that alleles with effects on IFN-{alpha} production might segregate in the founder population. In such case, the possibility to detect putative QTLs among the intercrosses is limited with the current experimental design.

Ab response was one of the first immune capacity trait to be examined by genetic analysis. The establishment of selection lines of mice with high and low Ab production to certain Ags (7) was followed by similar studies in domestic animals (12, 51, 52, 53, 54, 55). In most of these studies, medium high heritabilities were estimated. For the IgG response to the E. coli Ags O149 and K88, heritabilities of 0.29 and 0.45, respectively, were estimated in a population of crossbred Sw Yorkshire x Sw Landrace pigs (11). In addition, single genes/gene complexes influencing the Ab response have been identified. The effect of MHC loci on Ab response has been thoroughly studied in mice (6) and also in the pig (9, 56, 57, 58). A higher IgG response to the K88 Ag has been found in pigs expressing a dominantly inherited intestinal receptor for this Ag encoded by the K88acR locus on chromosome 13 (31). In the present study, two QTLs with strong effect on IgG levels to the E. coli Ags were identified in addition to several putative QTLs. One of these QTLs influenced prevaccination levels of IgG to K88 with pigs carrying domestic alleles at this locus having higher IgG levels, whereas the other QTL influenced the production of Abs to O149 after vaccination. However, none of these QTLs were located on chromosomes 7 (MHC) or 13 (K88acR), suggesting that, for these loci, there were no fixed differences in allele frequencies between the populations or that the effect was too small to be detected in this limited sample. Several studies in mice show that more than 10 loci, including the MHC and Igh loci, influence the Ab response in mice to various antigens (7, 24, 25). The role of MHC molecules in recognition of processed Ags and thus its influence on the elicited Ab response is well documented, but in concordance with the studies in mice, our results show that additional non-MHC loci are important for the Ab response. In that context it is notable that the locus that affected the production of Abs to K88 after natural, oral infections with E. coli did not influence the Ab production to K88 after intramuscularly immunization. Due to differences in route of entry, adjuvant activity, dose, and nature of the Ag, the two types of Ab responses studied most likely involve distinct events in Ag handling, which are under different genetic influence.

The pedigree used in the current study was designed to facilitate the mapping of genes controlling phenotypic differences between the European wild pig and domestic Sw Yorkshire pigs. Domestic and wild pigs show marked differences for a number of traits such as growth and fat deposition, and QTLs for those traits have also successfully been mapped (19, 30). Although differences in immune capacity between wild and domestic pigs have so far not been studied, it is likely that such differences exist due to the markedly different environmental conditions to which these populations are exposed. In the present study it would thus have been beneficial to measure the phenotypic traits also for the parental and F1 populations. Unfortunately, it was not possible to maintain reasonably large populations of wild pig and F1 animals due to practical and economical reasons. We therefore used a genome-wide test to look for differences between the two populations. The F2 animals were on average 50% wild pig, but the exact proportion of wild pig alleles varies between individuals due to Mendelian segregation. Using all marker data, the proportion of wild pig genome for each F2 animal was estimated. A significant effect of this parameter on the traits studied is expected if there is a net difference, summed over many loci, between alleles from the two populations. However, only PHA-induced IL-2 production and ADV-induced IFN-{alpha} production showed a significant difference between the two parental populations, with the wild pigs having higher levels. The power of the experiment to detect QTLs for immune capacity is thus lower than for traits like growth and fat deposition.

Although the pigs were clinically healthy, one cannot exclude that the observed genetic effects are exerted on responses to infectious agents or reflects genetic influence on susceptibility to infections because the study was performed on conventionally reared pigs. Differences in immune capacity due to divergent responses to potential "stressors" within the management (e.g. weaning (59, 60), transport (61, 62), and mixing and allocation (34, 63)), may also influence the results. Whether the observed QTL effects reflect differences in immune capacity between domestic and wild pigs, in susceptibility to subclinical infections and/or in the ability to cope with potential stressors, cannot be disentangled in the present study. Nevertheless, chromosomal regions harboring loci with influence on the examined traits were identified and warrants further studies to identify the actual genes involved.


   Acknowledgments
 
The animals were raised at the pig experimental station at the Swedish University of Agricultural Sciences in Uppsala under the supervision of Dr. K. Andersson and Ms. E. Ringmar-Cederberg. We are grateful to Ms. T. Basu, U. Gustafsson, and L. Fuxler for excellent technical assistance.


   Footnotes
 
1 This work was financially supported by the Swedish Council for Forestry and Agriculture Research. Back

2 Address correspondence and reprint requests to Dr. Inger Edfors-Lilja, Department of Engineering and Natural Sciences, University of Växjö, S-351 95 Växjö, Sweden. Back

3 Current address: Animal Health Trust, Center for Preventive Medicine, Lanwades Park, Kentford, CB8 7UU United Kingdom. Back

4 Abbreviations used in this paper: QTL, quantitative trait locus; Sw, Swedish; WBC, white blood cells; PMNL, polymorphonuclear leukocytes; CL, chemiluminiscence; ADV, Aujeszky’s disease virus. Back

Received for publication June 2, 1997. Accepted for publication March 23, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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