Biomedical subjects

T H Meuwissen

Publications and source records attributed to T H Meuwissen.

At least 19 recordsLinked to original sources

PubMed2001

Minimization of rate of inbreeding for small populations with overlapping generations.

We propose a method that minimizes the rate of inbreeding (delta F) for small unselected populations with overlapping generations and several reproductive age classes. It minimizes the increase in coancestry of parents and optimizes the contribution of each selection candidate. The carrying capacity of the population is limited to a fixed number of animals per year. When survival rate equalled 100%, only animals from the oldest age class were selected, which maximized the number of parents per generation, slowed down the turnover of generations and minimized the increase of coancestry across sublines. However, the population became split into sublines separated by age classes, which substantially increased inbreeding within sublines. Sublines were prevented by a restriction of selecting at least one sire and one dam from the second-oldest age class, which resulted in an L times lower delta F, where L equals the average generation interval of sires and dams. Minimum coancestry mating resulted in lower levels of inbreeding than random mating, but delta F was approximately the same. For schemes where the oldest animals were selected, delta F increased by 18-52% compared with the proposed method.

Age Factors↗

PubMed2001

Prediction of total genetic value using genome-wide dense marker maps.

Recent advances in molecular genetic techniques will make dense marker maps available and genotyping many individuals for these markers feasible. Here we attempted to estimate the effects of approximately 50,000 marker haplotypes simultaneously from a limited number of phenotypic records. A genome of 1000 cM was simulated with a marker spacing of 1 cM. The markers surrounding every 1-cM region were combined into marker haplotypes. Due to finite population size N(e) = 100, the marker haplotypes were in linkage disequilibrium with the QTL located between the markers. Using least squares, all haplotype effects could not be estimated simultaneously. When only the biggest effects were included, they were overestimated and the accuracy of predicting genetic values of the offspring of the recorded animals was only 0.32. Best linear unbiased prediction of haplotype effects assumed equal variances associated to each 1-cM chromosomal segment, which yielded an accuracy of 0.73, although this assumption was far from true. Bayesian methods that assumed a prior distribution of the variance associated with each chromosome segment increased this accuracy to 0.85, even when the prior was not correct. It was concluded that selection on genetic values predicted from markers could substantially increase the rate of genetic gain in animals and plants, especially if combined with reproductive techniques to shorten the generation interval.

Animals↗

PubMed2001

Transgenesis may affect farm animal welfare: a case for systematic risk assessment.

This paper considers (potentially) harmful consequences of transgenesis for farm animal welfare and examines the strategy of studying health and welfare of transgenic farm animals. Evidence is discussed showing that treatments imposed in the context of farm animal transgenesis are by no means biologically neutral and may compromise animal health and welfare. Factors posing a risk for the welfare of transgenic farm animals include integration of a transgene within an endogenous gene with possible loss of host gene function (insertional mutations), inappropriate transgene expression and exposure of the host to biologically active transgene-derived proteins, and in vitro reproductive technologies employed in the process of generating transgenic farm animals that may result in an increased incidence of difficult parturition and fetal and neonatal losses and the development of unusually large or otherwise abnormal offspring (large offspring syndrome). Critical components of a scheme for evaluating welfare of transgenic farm animals are identified, related to specific characteristics of transgenic animals and to factors that may interact with the effects of transgenesis. The feasibility of an evaluation of welfare of transgenic farm animals in practice is addressed against the background of the objectives and conditions of three successive stages in a long-term transgenic program. Concrete steps with regard to breeding and testing of transgenic farm animals are presented, considering three technologies to generate transgenic founders: microinjection, electroporation and nuclear transfer, and gene targeting including gene knockout. The proposed steps allow for unbiased estimations of the essential treatment effects, including hemi- and homozygous transgene effects as well as effects of in vitro reproductive technologies. It is suggested that the implementation of appropriate breeding and testing procedures should be accompanied by the use of a comprehensive welfare protocol, specifying which parameters to monitor, at which stages of the life of a farm animal, and in how many animals. Some prerequisites and ideas for such a protocol are given. It is anticipated that systematic research into the welfare of farm animals involved in transgenesis will facilitate the use of the safest experimental protocols as well as the selection and propagation of the healthiest animals and, thereby, enable technological progress that could be ethically justified.

Animal Welfare↗

PubMed2000

Fine mapping of quantitative trait loci using linkage disequilibria with closely linked marker loci.

A multimarker linkage disequilibrium mapping method was developed for the fine mapping of quantitative trait loci (QTL) using a dense marker map. The method compares the expected covariances between haplotype effects given a postulated QTL position to the covariances that are found in the data. The expected covariances between the haplotype effects are proportional to the probability that the QTL position is identical by descent (IBD) given the marker haplotype information, which is calculated using the genedropping method. Simulation results showed that a QTL was correctly positioned within a region of 3, 1.5, or 0.75 cM in 70, 62, and 68%, respectively, of the replicates using markers spaced at intervals of 1, 0.5, and 0.25 cM, respectively. These results were rather insensitive to the number of generations since the QTL occurred and to the effective population size, except that 10 generations yielded rather poor estimates of the QTL position. The position estimates of this multimarker disequilibrium mapping method were more accurate than those from a single marker transmission disequilibrium test. A general approach for identifying QTL is suggested, where several stages of disequilibrium mapping are used with increasingly dense marker spacing.

Chromosome Mapping↗

PubMed2000

The effect of adipocyte and heart fatty acid-binding protein genes on intramuscular fat and backfat content in Meishan crossbred pigs.

Effects of genetic variation in porcine adipocyte and heart fatty acid-binding protein genes, A-FABP and H-FABP, respectively, on intramuscular fat (IMF) content and backfat thickness (BFT) were examined in F2 crossbreds of Meishan and Western pigs. The involvement of each FABP gene in IMF accretion was studied to confirm previous results for Duroc pigs. The F2 crossbred pigs were genotyped for various markers including microsatellite sequences situated within both FABP genes. Linkage analysis assigned the A-FABP and H-FABP genes to marker intervals S0001-S0217 (20 cM) on SSC4 and Sw316-S0003 (16.6 cM) on SSC6, respectively, refining previous chromosomal assignments. Next, the role of both chromosome regions/genes on genetic variation in IMF content and BFT was studied by 1) screening SSC4 and SSC6 for QTL affecting both traits by performing a line-cross analysis and 2) estimation of the effect of individual A-FABP and H-FABP alleles on both traits. In the first analysis, suggestive and chromosome-wise significant evidence for a QTL affecting IMF was detected on SSC6. The H-FABP gene is a candidate gene for this effect because it resides within the large region containing this putative QTL. The second analysis showed a considerable but nonsignificant effect of H-FABP microsatellite alleles on IMF content. Suggestive evidence for a QTL affecting BFT was found on SSC6, but H-FABP was excluded as a candidate gene. In conclusion, present and previous results support involvement of H-FABP gene polymorphisms in IMF accretion independently from BFT in pigs. Therefore, implementation of these polymorphisms in marker-assisted selection to control IMF content independently from BFT may be considered. In contrast to previous findings for Duroc pigs, no evidence was found for an effect of the A-FABP gene on IMF or BFT in this population.

Adipocytes↗

PubMed2000

Strategies for estimating the parameters needed for different test-day models.

Currently, most analyses of parameters in test-day models involve two types of models: random regression, where various functions describe variability of (co)variances with regard to days in milk, and multiple traits, where observations in adjacent days in milk are treated as one trait. The methodologies used for estimation of parameters included Bayesian via Gibbs sampling, and REML in the form of derivative-free, expectation-maximization, or average-information algorithms. The first method is simpler and uses less memory but may need many rounds to produce posterior samples. In REML, however, the stopping point is well established. Because of computing limitations, the largest estimations of parameters were on fewer than 20,000 animals. The magnitude and pattern of heritabilities varied widely, which could be caused by simplifications in the model, overparameterization, small sample size, and unrepresentative samples. Patterns of heritability differ among random regression and multiple-trait models. Accurate parameters for large multi-trait random regression models may be difficult to obtain at the present time. Parameters that are sufficiently accurate in practice may be obtained outside the complete prediction model by a constructive approach, where parameters averaged over the lactation would be combined with several typical curves for (co)variances for days in milk. Obtained parameters could be used for any model, and could also aid in comparison of models.

Analysis of Variance↗

PubMed2000

Genetic parameters of legendre polynomials for first parity lactation curves.

Variance components of the covariance function coefficients in a random regression test-day model were estimated by Legendre polynomials up to a fifth order for first-parity records of Dutch dairy cows using Gibbs sampling. Two Legendre polynomials of equal order were used to model the random part of the lactation curve, one for the genetic component and one for permanent environment. Test-day records from cows registered between 1990 to 1996 and collected by regular milk recording were available. For the data set, 23,700 complete lactations were selected from 475 herds sired by 262 sires. Because the application of a random regression model is limited by computing capacity, we investigated the minimum order needed to fit the variance structure in the data sufficiently. Predictions of genetic and permanent environmental variance structures were compared with bivariate estimates on 30-d intervals. A third-order or higher polynomial modeled the shape of variance curves over DIM with sufficient accuracy for the genetic and permanent environment part. Also, the genetic correlation structure was fitted with sufficient accuracy by a third-order polynomial, but, for the permanent environmental component, a fourth order was needed. Because equal orders are suggested in the literature, a fourth-order Legendre polynomial is recommended in this study. However, a rank of three for the genetic covariance matrix and of four for permanent environment allows a simpler covariance function with a reduced number of parameters based on the eigenvalues and eigenvectors.

Animals↗

PubMed1999

Genetic variation at the porcine MYF-5 gene locus. Lack Of association with meat production traits.

The number of muscle fibers at birth appears to determine the maximal lean meat growth capacity in pigs and in cattle. Development of muscle fibers is regulated by the MyoD gene family consisting of MyoD1, myf-5, myf-6, and myogenin. Myf-5 is expressed in proliferating myoblasts. Here we report the genomic sequence of the porcine myf-5 gene with three microsatellites and two RFLPs located close to the coding sequences. Two of the microsatellites are located in the promoter region. The allelic distribution differs between breeds and selection lines. In two GY selection lines, 1216 pigs of two-generation families were genotyped for the HinfI RFLP, which was segregating in the GY breed. The other polymorphic loci are physically linked to this RFLP locus, and therefore the results can be extrapolated to these loci. Statistical analysis revealed no association with birth weight, growth rate, weight at slaughter age, carcass meat weight, and backfat thickness. Thus, in this study myf-5 did not explain genetic variation in meat (muscle) development in pigs.

Animals↗

PubMed1999

Effect of genetic variants of the heart fatty acid-binding protein gene on intramuscular fat and performance traits in pigs.

In order to find genetic markers to improve the meat quality of pigs by breeding we studied the relationship between variation in the heart fatty acid-binding protein (H-FABP) gene (FABP3) and intramuscular fat (IMF) content. To estimate the effect of H-FABP, pigs from two Duroc populations were selectively mated in such a way that at least two genotypes were present in each litter. In total, data from 983 pigs and pedigree information from three preceding generations were analyzed. Offspring were tested for IMF content as well as backfat thickness (BFT), BW, and drip loss of the meat (DRIP). All pigs were assigned to H-FABP RFLP genotype classes either by the assessed genotype (75%) or based on a probability score determined according to genotypic information of their relatives (25%). Contrasts were detected between homozygous H-FABP RFLP genotype classes for IMF content (.4%, P < .05), BFT (.6 mm, P < .01), and BW (2.4 kg, P < .10). No significant contrasts were detected for DRIP. Results for IMF content, BFT, and BW were confirmed when only genotyped animals were analyzed. Variation in BFT partially explained the effect on IMF content. Although other closely linked genes on porcine chromosome 6 might be responsible for the observed effect, interference of the halothane gene was excluded because all parental animals were noncarriers. In conclusion, H-FABP RFLP can be used as markers to select for increased IMF content and growth in breeding programs.

Adipose Tissue↗

PubMed1999

Influences of myogenin genotypes on birth weight, growth rate, carcass weight, backfat thickness, and lean weight of pigs.

Lean weight is related to muscle fiber number. Muscle fiber formation (myogenesis) occurs only during embryonic development when it is under the control of the MyoD gene family consisting of myogenin, MyoD1, myf-5, and myf-6. Myogenin has a central position within the MyoD gene family because myogenin expression abrogates myoblast proliferation potential and regulates the differentiation of single nucleated myoblasts into multinucleated myofibers. Thus, myogenin genotype could be related to variation in the number of muscle fibers formed, leading to variation in muscle mass and, thus, lean weight. A polymorphism at the porcine myogenin locus was associated with birth weight, growth rate, lean weight at 200 d, and backfat thickness. Yorkshire pigs from two commercial lines were genotyped, and crosses between heterozygous pigs and heterozygous and homozygous pigs were made. Resulting litters were genotyped, and phenotypic data were collected. Significant differences were found between the two homozygous myogenin genotypes for birth weight, growth rate, and lean weight, but not for backfat thickness. Variation at the myogenin locus explained 4% of the total phenotypic variation in birth weight, growth rate, and carcass weight, and 5.8% of the total variation in lean weight. We conclude that myogenin genotype influences porcine growth rate and muscle mass.

Adipose Tissue↗

PubMed1999

Prediction of daily milk yields from a limited number of test days using test day models.

A data set of weekly milk yield records was used to compare different test day models for their ability to interpolate and extrapolate missing milk yields. The criteria to compare the models were 1) the (co)variance structure modeled compared with the observed (co)variance structure in the data and 2) mean square error of predictions of missing observations (MSEP), which compared the predicted value of a missing record to the known value of the record. The test day models used were LEG(m), which are Legendre polynomials with an order of fit of m, and EXP, which is an exponential lactation function. When fitting the LEG(m) models, criteria 1) and 2) generally improved with an increasing order of fit as expected. The model EXP, which contains three random regression coefficients, was between LEG(1) and LEG(2), which contain two and three coefficients, respectively. The improvement of the criteria with m in LEG(m) became negligible after LEG(5). Thus, a 5th order Legendre polynomial yields a good fit with a minimum number of parameters. Also, the correlation structure of milk yields among days in milk modeled by LEG(5) resembled the correlation structure that was observed in the data. However, the modeled variances at the end of lactation were larger than those observed in the data except when LEG(0) was used. Legendre polynomials with a fit less than five yielded correlation structures that clearly deviated from the observed correlations, especially in the case of LEG(0). Overall, LEG(5) is preferred to develop a genetic TDM for breeding value estimation.

Analysis of Variance↗

PubMed1998

The adipocyte fatty acid-binding protein locus: characterization and association with intramuscular fat content in pigs.

The porcine A-FABP gene (FABP4) was isolated and sequenced to study the role of A-FABP in the differentiation of intramuscular fat (IMF) accretion in pigs. The coding sequence of the porcine A-FABP gene is highly conserved across human, mouse, and rat. Moreover, all the functionally important amino acids are conserved. This high similarity extends into the first 270 bp of the 5' upstream region. Within this region, a 56-bp nucleotide sequence was completely identical with the corresponding sequence in the mouse A-FABP gene, which contains the transcription factor binding sites for C/EBP and AP-1, and is implicated in the differentiation-dependent regulation of A-FABP. The A-FABP gene was assigned to porcine Chromosome (Chr) 4 by a porcine sequence-specific PCR on a cell hybrid panel, fully consistent with comparative mapping data with human and mouse. In the first intron of the porcine A-FABP gene, a microsatellite sequence was detected that was polymorphic for all six pig breeds tested. This genetic variation within the A-FABP gene was associated with differences in IMF content and possibly growth in a Duroc population, whereas no effect on backfat thickness and drip loss of the meat were detected. A considerable and significant contrast of approximately 1% IMF was observed between certain genotype classes. We conclude that the A-FABP locus is involved in the regulation of intramuscular fat accretion in Duroc pigs.

Adipose Tissue↗

PubMed1998

Maximizing the response of selection with a predefined rate of inbreeding: overlapping generations.

In a breeding scheme, the aim is high rates of genetic gain with limited inbreeding. A dynamic selection rule is developed that maximizes selection response in populations with overlapping generations. The rule maximizes the genetic merit of selected animals while limiting the average relationship of the population after the current round of selection. The latter is shown to limit the contribution of the current population to the future inbreeding. The rule accounts for the selection of some candidates during previous selection rounds and for the expected future contributions of the selection candidates. Inputs for the rule are the BLUP breeding values and ages of selection candidates, the relationship matrix of all animals, and contributions of animals during previous selection rounds. Output is the optimal number of offspring for each candidate. Computer simulations of dairy cattle nucleus schemes showed that predefined rates of inbreeding were actually achieved, without compromising long-term selection response, at least up to 20 yr of selection. At the same rates of inbreeding, the dynamic selection rule obtained up to 44% more genetic gain than direct selection for BLUP breeding values. The advantage of the dynamic rule over BLUP selection decreased with increasing population sizes and with greater predefined rates of inbreeding. Consequently, the dynamic rule should be especially useful in small selection schemes in which relatively low rates of inbreeding are desired.

Age Factors↗

PubMed1998

Genetics of the interval from weaning to estrus in first-litter sows: correlated responses.

The objective of this study was to evaluate relationships between rebreeding performance and growth performance (n = 3,777 gilts) and rebreeding performance and reproductive performance (n = 2,242 sows). Our data were from a selection experiment for shorter intervals from weaning to estrus after the first parity (IWE), involving Dutch Landrace pigs, in which a selection line and a control line without selection were maintained for eight generations. Relationships were evaluated before and after transforming IWE to normal interval (NI; IWE < or = 7 d), prolonged interval (PI; IWE > 7 d), and incidence of a prolonged interval (INC). Heritabilities of NI, PI, and INC were .18, .17, and .27. Within-line phenotypic and genetic trends in growth and reproductive performance were not different from zero and did not diverge as a correlated response to the selection applied. Phenotypic correlations between IWE, NI, or PI and growth or reproductive performance were low and ranged from -.14 to .11. Genetic correlations were higher, and, for the majority of traits, the genetic correlations with NI and PI had a different sign. Phenotypic and genetic contrasts between sows with NI and sows with PI different from zero indicated that INC may increase as a correlated response to selection for reproductive performance. Analyses using untransformed IWE or data from populations selected for rebreeding performance may underestimate the correlated response in IWE due to selection on economically important traits.

Animals↗

PubMed1998

Optimizing pure line breeding strategies utilizing reproductive technologies.

The development of new reproductive techniques has had a great effect on schemes for dairy cattle improvement; AI resulted in progeny-testing schemes, and, more recently, multiple ovulation and embryo transfer has resulted in nucleus breeding schemes. In traditional breeding schemes, the use of multiple ovulation and embryo transfer resulted in only small increases of genetic gains because the selection intensity of bull dams was already high, but the selection intensity of cows in nucleus breeding schemes increased considerably. This increase makes nucleus schemes very competitive, especially when in vitro maturation and fertilization is used to increase female reproductive rates further. The increased genetic gain results in the selection of young females (i.e., optimal generation intervals are shortened). The combined effect of multiple ovulation and embryo transfer and shorter generation intervals increases the rate of gain by approximately 15% but also increases the rate of inbreeding and variances of the selection response (i.e., the risk of the breeding scheme) by about 80%. Recently, selection methods have been developed to reduce the rates of inbreeding or the variance of the selection response in breeding schemes. A scheme that maximized the selection differential while constraining the rate of inbreeding yielded about 30 to 60% more selection response than selection for BLUP estimated breeding value at the same rate of inbreeding. For the future, the combination of juvenile predictors of genetic merit (e.g., DNA markers) and techniques that further increase female reproductive rates seem very promising methods to increase the rates of genetic gain. As an example, the genetic gain of an optimized hybrid nucleus scheme could be increased 24% by the combined use of juvenile predictors and in vitro maturation and fertilization. Fertilization of fetal embryos was predicted to increase rates of gain by up to 18%.

Animals↗

PubMed1997

Estimation of effects of quantitative trait loci in large complex pedigrees.

A method was derived to estimate effects of quantitative trait loci (QTL) using incomplete genotype information in large outbreeding populations with complex pedigrees. The method accounts for background genes by estimating polygenic effects. The basic equations used are very similar to the usual linear mixed model equations for polygenic models, and segregation analysis was used to estimate the probabilities of the QTL genotypes for each animal. Method R was used to estimate the polygenic heritability simultaneously with the QTL effects. Also, initial allele frequencies were estimated. The method was tested in a simulated data set of 10,000 animals evenly distributed over 10 generations, where 0, 400 or 10,000 animals were genotyped for a candidate gene. In the absence of selection, the bias of the QTL estimates was < 2%. Selection biased the estimate of the Aa genotype slightly, when zero animals were genotyped. Estimates of the polygenic heritability were 0.251 and 0.257, in absence and presence of selection, respectively, while the simulated value was 0.25. Although not tested in this study, marker information could be accommodated by adjusting the transmission probabilities of the genotypes from parent to offspring according to the marker information. This renders a QTL mapping study in large multi-generation pedigrees possible.

Animals↗

PubMed1997

Maximizing the response of selection with a predefined rate of inbreeding.

A method was derived that maximizes the genetic level of selected animals while constraining their average coancestry to a predefined value. The average coancestry of the selected parents equals the inbreeding level in the next generation, so that rates of inbreeding were controlled. When this method was applied for several generations of selection, stable rates of genetic gain were attained, which indicates that the method could control the short- and long-term effects of selection on inbreeding. At equal rates of inbreeding, genetic gains were 21 to 60% greater than that with selection for BLUP-EBV, because of increased selection differentials. The difference was larger when the desirable rate of inbreeding was smallest. Selection with a constraint on inbreeding required only EBV of, and relationships between, the selection candidates and is therefore easy to apply in practice. The optimal solution is expressed in genetic contributions of selection candidates to the next generation, which is equivalent to numbers of offspring per candidate. These optimal numbers of offspring may be difficult to attain because of female reproductive limitations. The optimal method could be adapted to situations with additional reproductive constraints. The method can also be used to constrain the variance of response by restricting the average prediction error variance of the selected animals.

Animal Husbandry↗

PubMed1995

Maximizing selection efficiency for categorical traits.

Genetic improvement of categorically recorded traits is hampered because information content of categorical records is low and ordinary linear breeding value estimation methods do not apply theoretically. The ordinary animal or linear mixed model (LMM), which ignored the categorical nature of the trait, is compared to a generalized linear mixed model (GLMMp) that assumes a linear mixed model for an underlying continuous variable. The GLMMp takes full account of the categorical nature of the trait and is a straightforward extension of LMM. In a closed nucleus breeding scheme (e.g., cattle, pigs, or poultry), rates of genetic gain increased by 1 to 2%, when GLMMp was used instead of LMM. Rates of genetic gain increased by 7 to 20%, when the best sires were used on the best herds (i.e., when there was some confounding between sire and herd effects). When considering a binary trait (e.g., disease incidence) initial incidences of 25% could be reduced to 2.8% within 10 generations of selection. Rates of gain can be increased by up to 84% by gathering more information on high-incidence categories (i.e., by dividing these categories into subcategories). Subdividing low-incidence categories (e.g., splitting diseased animals into moderately and severely diseased) hardly increased rates of gain. Direct recording of the underlying variable, which requires uncovering of the physiological background of the categorical trait, yielded 109 to 278% more genetic gain than selection for a binary trait.

Animals↗