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Biomedical subjects

J C Dekkers

Publications and source records attributed to J C Dekkers.

At least 19 recordsLinked to original sources

Biopsychosocial mediators and moderators of stress-health relationships in patients with recently diagnosed rheumatoid arthritis.

OBJECTIVE: To investigate the mediating and moderating roles of social support, coping, and physiological variables in the relationship between life events and health status. METHODS: Psychological and biological measurements were taken in 54 patients (38 women, 16 men, mean age +/- SD 56 +/-14.4 years) with recently diagnosed rheumatoid arthritis (RA). RESULTS: Life events were correlated with psychological distress, but not with disease activity. No mediators for the relationship of life events with psychological well-being and disease activity were observed. In 40 tests, 4 moderators were found: Problem-focused coping, perceived support, diastolic blood pressure, and total number of lymphocytes were moderators of the relationship between daily hassles and health status (P < or = 0.05). CONCLUSION: Our study provides limited support for the notion that the interactions of life stress with biopsychosocial variables have an impact on health. None of these variables were found to be crucial mediators of stress-health associations in recently diagnosed patients with RA, but some provocative evidence was given that biopsychosocial variables may have a minor impact on stress-health relationships.

Adaptation, Psychological↗

A molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. I. Growth and body composition.

Genome scans can be employed to identify chromosomal regions and eventually genes (quantitative trait loci or QTL) that control quantitative traits of economic importance. A three-generation resource family was developed by using two Berkshire grand sires and nine Yorkshire grand dams to detect QTL for growth and body composition traits in pigs. A total of 525 F2 progeny were produced from 65 matings. All F2 animals were phenotyped for birth weight, 16-day weight, growth rate, carcass weight, carcass length, back fat thickness, and loin eye area. Animals were genotyped for 125 microsatellite markers covering the genome. Least squares regression interval mapping was used for QTL detection. All carcass traits were adjusted for live weight at slaughter. A total of 16 significant QTL, as determined by a permutation test, were detected at the 5% chromosome-wise level for growth traits on Chromosomes (Chrs) 1, 2, 3, 4, 6, 7, 8, 9, 11, 13, 14, and X, of which two were significant at the 5% genome-wise level and two at the 1% genome-wise level (on Chrs 1, 2, and 4). For composition traits, 20 QTL were significant at the 5% chromosome-wise level (on Chrs 1, 4, 5, 6, 7, 12, 13, 14, 18), of which one was significant at the 5% genome-wise level and three were significant at the 1% genome-wise level (on Chrs 1, 5, and 7). For several QTL the favorable allele originated from the breed with the lower trait mean.

Animals↗

A molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. II. Meat and muscle composition.

Molecular genetic markers can be used to identify chromosomal regions that contain quantitative trait loci (QTL) that control meat quality and muscle composition traits in farm animals. To study this in pigs, a resource family was generated from a cross between two Berkshire grand sires and nine Yorkshire grand dams. A total of 525 F2 progeny from 65 matings of F1 parents were produced. Phenotypic data on 28 meat quality traits (drip loss, water holding capacity, firmness, color, marbling, percentage cholesterol, ultimate pH, fiber type, and several sensory panel and cooking traits) were collected on the F2 animals. Animals were genotyped for 125 microsatellite markers covering the entire genome. Least squares regression interval mapping was used for QTL detection. Significance thresholds were determined by permutation tests. A total of 60 QTL were detected at the 5% chromosome level for meat quality traits, on Chrs 1, 2, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 17, 18, and X, of which 9 and 1 QTL were significant at the 5% and 1% genome-wise levels (on Chrs 1, 5, 12, 15, and 17), respectively.

Adipose Tissue↗

Potential gain from optimizing multigeneration selection on an identified quantitative trait locus.

The potential extra response that can be obtained from the optimal use of a known QTL in selection by optimizing weights in an index of breeding value for the QTL and polygenic EBV was investigated for a range of parameters. Optimal strategies were derived for a deterministic model of simultaneous selection on a QTL and polygenic effects using optimal control theory. Responses over 10 generations to the following selection strategies were compared: 1) standard QTL selection, with QTL weights equal to 1, 2) optimal QTL selection, 3) stepwise single-generation optimal QTL selection, and 4) non-QTL selection based on phenotype. Cumulative discounted response with discount rates of 10 or 30% per generation were evaluated and used as objective for optimal selection strategies. Optimal selection balanced the conflict between short- and long-term responses and gave greater cumulative discounted response than standard QTL selection of up to 20%, but less than 5% for most cases. Discount rate had limited impact. For a QTL with an additive effect of one polygenic standard deviation, cumulative discounted response from optimal QTL selection was less than 5% greater than response for non-QTL selection for most cases. Exceptions were traits with low heritability and recessive QTL at low frequency, for which extra response was up to 55% greater. Stepwise optimal selection resulted in less cumulative discounted response than standard QTL selection for QTL with negative dominance. The benefit of optimal over stepwise optimal selection was limited (less than 4%) for most cases, except for overdominant QTL. These results indicate that optimizing selection on an identified QTL can result in greater responses to selection but that extra responses tend to be limited for the situations studied here of single-stage purebred selection on a single QTL for a trait observed on both sexes.

Animals↗

Bayesian inference for categorical traits with an application to variance component estimation.

We implemented statistical models of Bayesian inference that included direct and maternal genetic effects for genetic parameter estimation of categorical traits by Gibbs sampling. The estimation errors and variances of estimates of animal versus sire and maternal grandsire models, of linear versus threshold models, of single-trait versus multiple-trait models, and of treating herd-year-season as fixed versus random effects in the model were compared. The results indicated that linear models yielded biased estimates of genetic parameters for categorical traits. The animal model was improper for analysis of categorical traits using a threshold model and the Gibbs sampler. Moreover, linear versus threshold models and animal versus sire-maternal grandsire models resulted in larger Monte Carlo errors and increased auto-correlations among posterior samples. Treating herd-year-seasons as random effects in the threshold models decreased the Monte Carlo error, auto-correlations, and the variances of estimates. Efficiency of the single-trait threshold sire model, as measured by the variance of the estimates, was lower than for a multiple-trait model that included a correlated continuous trait, but both estimates were unbiased. Therefore, the threshold single-trait sire and maternal grandsire model is a feasible alternative to the multiple-trait model for analysis of variance components of categorical traits affected by direct and maternal genetic factors.

Animals↗

Experimentally challenged reactivity of the hypothalamic pituitary adrenal axis in patients with recently diagnosed rheumatoid arthritis.

OBJECTIVE: There is evidence that the hypothalamic pituitary adrenal (HPA) axis is subresponsive in patients with rheumatoid arthritis (RA). We assessed HPA axis responses to experimental stressors mimicking daily life challenges in patients with RA to determine whether HPA axis activity is associated with Th1 and Th2 activity. METHODS: ACTH and cortisol responses in reaction to the succession of a bicycle ergometer task, a cold pressor task, and a computerized Stroop Color-Word interference test, as well as basal Th1 and Th2 cell activity, were assessed in 29 patients (21 female, 8 male) with recently diagnosed RA (mean disease duration 29 wks, range 5-69), mean age 55.7 years, none receiving glucocorticoid treatment, and 30 (20 female, 10 male) healthy age and sex matched controls (mean age 54.1 yrs). RESULTS: Mean ACTH and cortisol levels did not differ between the groups (p > 0.10). Patients tended to have a less pronounced ACTH response (F2.50 = 2.7, p = 0.08) and had a significantly smaller cortisol response (P F2.50 = 6.1, p < 0.01) than healthy controls in reaction to the stressors. This difference in cortisol response was reduced, but remained significant when ACTH responsiveness was accounted for by entering it as a covariate (P F2.49 = 3.7, p = 0.03). ACTH and cortisol levels and responses were not associated (all p > 0.19) with basal interferon-gamma and interleukin 4 as reflections of Th1 and Th2 cell activity, respectively. HPA axis activity was not linked to current disease activity. CONCLUSION: Our findings show reduced HPA axis responsiveness in RA patients with recent diagnosis receiving longterm medication that is suggested to be located both at a hypothalamic/pituitary and at an adrenal level. It appears that common HPA axis activity accomplishes low amounts of cortisol release, which makes it difficult to determine an influence of endogenous cortisol changes on the Th1/Th2 balance.

Adrenocorticotropic Hormone↗

Power of quantitative trait locus mapping for polygenic binary traits using generalized and regression interval mapping in multi-family half-sib designs.

A generalized interval mapping (GIM) method to map quantitative trait loci (QTL) for binary polygenic traits in a multi-family half-sib design is developed based on threshold theory and implemented using a Newton-Raphson algorithm. Statistical power and bias of QTL mapping for binary traits by GIM is compared with linear regression interval mapping (RIM) using simulation. Data on 20 paternal half-sib families were simulated with two genetic markers that bracketed an additive QTL. Data simulated and analysed were: (1) data on the underlying normally distributed liability (NDL) scale, (2) binary data created by truncating NDL data based on three thresholds yielding data sets with three different incidences, and (3) NDL data with polygenic and QTL effects reduced by a proportion equal to the ratio of the heritabilities on the binary versus NDL scale (reduced-NDL). Binary data were simulated with and without systematic environmental (herd) effects in an unbalanced design. GIM and RIM gave similar power to detect the QTL and similar estimates of QTL location, effects and variances. Presence of fixed effects caused differences in bias between RIM and GIM, where GIM showed smaller bias which was affected less by incidence. The original NDL data had higher power and lower bias in QTL parameter estimates than binary and reduced-NDL data. RIM for reduced-NDL and binary data gave similar power and estimates of QTL parameters, indicating that the impact of the binary nature of data on QTL analysis is equivalent to its impact on heritability.

Algorithms↗

A quantitative approach to classifying Holstein cows based on antibody responsiveness and its relationship to peripartum mastitis occurrence.

A quantitative approach was developed to classify Holstein cows and heifers based on phenotypic variation of serum antibody response and to determine associations with peripartum mastitis. Using an index, 136 cows and heifers were classified into high (Group 1), average (Group 2), or low (Group 3) antibody groups following immunization with ovalbumin at wk -8, -3, and 0 relative to parturition. The ranking of groups based on the quantitative index of serum antibody response to ovalbumin were similar for sera and whey antibody such that Group 1 > Group 2 > Group 3. Animals were also vaccinated with Escherichia coli J5 (Rhône Mérieux, Lenexa, KS) at wk -8 and -3 relative to parturition. The ranking of groups for E. coli J5 was similar to that observed for serum and whey antibody to ovalbumin. Serum and whey IgG1 and IgG2 concentrations were measured at wk 0, 3, and 6 but differences between groups were not significant. There was no occurrence of mastitis for Group 1 animals in two of the herds. In contrast, Group 1 animals from the third herd had the highest occurrence of mastitis; however, these cases all occurred in first-parity heifers. According to pooled data across all herds, Group 3 animals had the highest occurrence of mastitis. Heritability estimates of serum antibody response to ovalbumin varied between 0.32 to 0.64 depending on week relative to parturition. Heritability estimates of serum antibody response to E. coli J5 also varied between 0.13 to 0.88 depending upon week relative to parturition. These results indicate that high peripartum antibody may be beneficial in some herds.

Animals↗

Relationships between energy balance and health traits of dairy cattle in early lactation.

The objective of the study was to calculate phenotypic relationships between energy balance in early lactation and health and reproduction in that lactation. Data were 26,701 daily records of dry matter intake and milk production, periodic measures of milk composition and body weight, and all health and reproductive information from 140 multiparous Holstein cows. Daily energy balance was calculated by multiplying feed intake by the concentration of energy of the ration and subtracting the amount of energy required for maintenance (based on parity and body weight) and for milk production (based on yield and concentrations of fat, protein, and lactose). Six measures of energy balance were defined: mean daily energy balance during the first 20, 50, and 100 d of lactation; minimum daily energy balance; days in negative energy balance; and total energy deficit. Measures of health were the numbers of occurrences of each of the following during lactation: all udder problems, mastitis, all locomotive problems, laminitis, digestive problems, and reproductive problems. Reproductive traits were the number of days to first observed estrus and number of inseminations. Several significant relationships between energy balance and health were observed. Increased digestive and locomotive problems were associated with longer and more extreme periods of negative energy balance.

Animal Feed↗

Associations of the bovine major histocompatibility complex DRB3 (BoLA-DRB3) with production traits in Canadian dairy cattle.

Associations of two alleles of the bovine major histocompatibility complex DRB3 gene (BoLA-DRB3) with lowered somatic cell score (SCS) and occurrence of disease (BoLA-DRB3.2* 16 and *23, respectively) have previously been documented. The objective of this study was to evaluate potential relationships between BoLA-DRB3 alleles with production traits, namely 305-day milk, milk fat and milk protein yield, in a population of Canadian dairy cattle (Holstein, n = 835 and Jersey, n = 66) over the course of two lactations. No significant associations were detected between BoLA alleles and production traits in Jerseys. In Holsteins, alleles *16 and *23 also did not show associations with production traits but allele *8 was significantly associated with increased 305-day milk, fat and protein yields in the previous lactation (the lactation prior to immunization with a gram negative core antigen vaccine), and with increased protein production in the subsequent (with reference to the time of immunization) lactation. Allele *22 was associated with decreased milk and protein yield in both previous and subsequent lactations. Therefore, it can be concluded that increasing or decreasing the frequency of BoLA alleles *16 and *23 to reduce SCS or increase resistance to mastitis in this population would not have adverse effects on production in this population, and that certain BoLA alleles (*8 and *22) are associated with altered production traits in Canadian Holsteins.

Alleles↗

Comparison of methods for genetic evaluation of sires for survival of their daughters in the first three lactations.

Several approaches for analysis of survival in the first three lactations were compared using data from approximately 700,000 Canadian Holsteins. Two approaches (linear model and threshold model) were used to analyze a binary measure of survival. Other approaches were survival analyses to evaluate two measures of the number of days that cows were in milk during their first three lactations. One measure restricted days per lactation to < or = 305; the other was based on the actual number of days in milk without an upper limit on days per lactation. Variance components and breeding values (EBV) were estimated. Sire models were used almost exclusively, but one set of EBV was obtained using a linear animal model. Effects in the models were herd-year of calving, age at first calving, interaction of several factors related to herd, and production. Thus, all EBV were for functional herd life. Heritabilities were approximately 0.04, 0.07, and 0.10 from linear, threshold, and survival analyses, respectively. Correlations among sire EBV from all analyses using sire models were high, particularly for linear and threshold models (0.98). In contrast, correlations of EBV from sire models with EBV from the linear animal model were less than 0.90, regardless of the approach taken. In Canada, the current linear animal model remains in use for sire evaluation of herd life, but research with survival analyses will continue.

Animals↗

An epidemiologic study of disease in 32 registered Holstein dairy herds in British Columbia.

Data recorded in a herd health management system were obtained from 32 registered Holstein dairy herds from British Columbia. Frequencies of disease were described, and the effect of herd, age, year, season, and the interrelationships between diseases within a lactation on the occurrence of disease were evaluated. Lactational incidence rates were computed for diseases with a short period of risk (ie, udder edema, milk fever, retained placenta, metritis, displaced abomasum, and ketosis), whereas for diseases with a longer period of risk (ie, cystic ovaries, mastitis and stable footrot), incidence densities were calculated. Overall, the disease incidence was low and showed an increase in frequency by year, which we attributed to more observing and complete recording by the owner, rather than an actual increase in disease incidence. Most diseases occurred early in lactation and their frequency increased with lactation number; the exception was udder edema, which occurred mainly during the first 2 lactations. An informal path model of disease interrelationships was made conditional on herd. Based on the results we inferred 2 independent pathways: one started by udder edema, and the other by milk fever. Udder edema was directly associated with mastitis occurrence from 0 to 30 d in lactation, metritis, and cystic ovaries. Mastitis from 0-30 d in lactation increased the risk of both mastitis from 31-150 d in lactation and cystic ovaries. Both of these increased the risk of late lactation mastitis. Milk fever was directly related with displaced abomasum, which increased the risk of footrot. In general, diseases that occurred in early lactation tended to increase the risk of other diseases later in lactation.

Animals↗

Associations of the bovine major histocompatibility complex DRB3 (BoLA-DRB3) alleles with occurrence of disease and milk somatic cell score in Canadian dairy cattle.

Potential associations were investigated between bovine leucocyte antigen (BoLA) alleles and occurrence of disease. Cows (Holstein n = 835; Jersey n = 66) were examined for polymorphisms of the second exon of the BoLA-DRB3 gene, using the polymerase chain reaction (PCR), followed by digestion of the amplified fragments with three restriction endonucleases. Disease occurrences were recorded for each cow throughout one lactation. Milk somatic cell count data were retrieved through the Dairy Herd Improvement records and converted to somatic cell score (SCS). There were no effects of BoLA alleles on SCS in Jersey cows, but BoLA-DRB3.2*16 was significantly associated (P < or = 0.05) with lower SCS in Holsteins. Since the number of Jerseys was relatively small and prevalence of diseases in this population was low, health records of Jerseys were not analyzed further. BoLA associations with occurrence of disease in Holsteins were investigated using a log-linear model. There was a significant (P < or = 0.05) association between BoLA-DRB3.2*23 and occurrence of severe mastitis, from which coliforms were the most commonly isolated bacteria. The BoLA allele *3 was associated with a lower risk of retained placenta (P < or = 0.05) and alleles *16 (P < or = 0.05) and *22 (P < or = 0.05) with a lower risk of cystic ovarian disease. Although more studies are required to confirm the present findings, it can be concluded that BoLA alleles may have potential usefulness as genetic markers of higher or lower risk of disease occurrence in cows.

Alleles↗

Least squares interval mapping of quantitative trait loci under the infinitesimal genetic model in outbred populations.

Genetic marker and phenotypic data for a quantitative trait were simulated on 20 paternal half-sib families with 100 progeny to investigate properties of within-family-regression interval mapping of a postulated single quantitative trait locus (QTL) in a marker interval under the infinitesimal genetic model, which has been the basis of the application of quantitative genetics to genetic improvement programs, and to investigate use of the infinitesimal model as null hypothesis in testing for presence of a major QTL. Genetic effects on the marked chromosome were generated based on a major gene model, which simulated a central biallelic QTL, or based on 101 biallelic QTL of equal effect, which approximated the infinitesimal model. The marked chromosome contained 0, 3.3%, 13.3%, or 33.3% of genetic variance and heritability was 0.25 or 0.70. Under the polygenic model with 3.3% of genetic variance on the marked chromosome, which corresponds to the infinitesimal model for the bovine, significant QTL effects were found for individual families. Correlations between estimates of QTL effects and true chromosome substitution effects were 0.29 and 0.47 for heritabilities of 0.25 and 0.70 but up to 0.85 with 33.3% of polygenic variance on the marked chromosome. These results illustrate the potential of marker-assisted selection even under the infinitesimal genetic model. Power of tests for presence of QTL was substantially reduced when the polygenic model with 3.3% of genetic variance on the chromosome was used as a null hypothesis. The ability to determine whether genetic variance on a chromosome was contributed by a single QTL of major effect or a large number of QTL with minor effects, corresponding to the infinitesimal model, was limited.

Chromosome Mapping↗

Applying breeding objectives to dairy cattle improvement.

Otherwise well-researched definitions of breeding objectives and selection criteria may never be used in practice if those definitions do not take into account the perceptions and wishes of the breeders for whom they are designed. Finding selection criteria that are widely accepted and implemented is a daunting task that requires considerable time and full interaction between the scientists and the industry. We review various aspects of this process and, in particular, how scientific principles can be used to ensure that the outcome best meets both the perceptions and needs of the users while remaining as close as possible to the technical economic optimum. Alternative methods of presenting and delivering selection indexes, such as index expression, index formulation, focus on response to selection rather than on index weights, construction of component indexes, and the use of direct accounting for costs of constraints rather than rescaling methods can all help in improving acceptance of an index. Development and implementation of selection criteria also involve consideration of the selective mating decisions that form an integral part of selection decisions in the field. The technical basis of factors that foster emphasis on individual mating decisions in the field are discussed in relation to formulation of the breeding goal and selection index and in relation to nonlinear economic and genetic parameters. Strategies that focus on use of a linear index for the selection of sires and dams followed by selective mating of selected parents have the greatest potential for implementation in the industry. We focus on examples taken from the Canadian dairy industry, but principles apply generally.

Animals↗

Genetic evaluation for herd life in Canada.

Methods were developed for the national genetic evaluation of herd life for Canadian Holstein sires. The genetic evaluations incorporate information from survival (direct herd life) and information from conformation traits that are related to herd life (indirect herd life) after adjustment for production in first lactation to remove the effect of culling for production. Direct genetic evaluations for herd life were based on survival in each of the first three lactations, which was analyzed using a multiple-trait animal model. Sire evaluations thus obtained for survival in each of the first three lactations were combined based on their economic weights into an overall sire evaluation for direct herd life. Sire evaluations for indirect herd life were based on an index of sire evaluations for mammary system, feet and legs, rump, and capacity. A multiple-trait sire model based on multiple-trait across country evaluation methodology was used to combine direct and indirect genetic evaluations for herd life into an overall genetic evaluation for herd life. Sire evaluations for herd life were expressed in estimated transmitting ability as the number of lactations and represent expected differences among daughters in functional herd life (number of lactations); the average functional herd life was set equal to three lactations. Estimated transmitting abilities were normally distributed and ranged from 2.31 to 3.43 lactations.

Animals↗

Alteration in immune responsiveness during the peripartum period and its ramification on dairy cow and calf health.

Substantial evidence indicates that innate and acquired defense mechanisms are lowest from 3 wk precalving to 3 wk postcalving. This lowered responsiveness includes aspects of systemic and mammary gland immunity that may account, at least in part, for the increased incidence of peripartum disease. The physical and metabolic stresses of pregnancy, calving, and lactation may contribute to this decrease in host resistance and the subsequent increase in disease incidence. However, variation among cows in their host resistance mechanisms suggests that genotype and phenotype may possibly be used to identify cows that are able to mount beneficial immune responses over the periparturient period. Our own studies suggest that cows may be categorized as high or low responders based on the peripartum antibody responses to ovalbumin and Escherichia coli J5. Low responders were hyporesponsive to these test antigens and had a higher incidence of peripartum diseases, particularly mastitis. In many species, a functional link exists between the immune and endocrine systems, and, during periods of stress or physical injury, neuropeptides and neuroendocrine hormones function as immunomodulators. Initial investigations of peripartum cows reveal positive relationships between growth hormone kinetics and profiles of antibody response. Whether hormone fluctuations during the periparturient period are responsible for the alterations observed in immune responsiveness remains uncertain.

Animals↗