Biomedical subjects

J I Weller

Publications and source records attributed to J I Weller.

At least 37 records · Page 2Linked to original sources

PubMed1998

Host factors affecting the homologous and heterologous immune response of cattle to FMDV: genetic background, age, virus strains and route of administration.

Sixty bulls were tested for antibodies to the heterologous serotype C1 of FMDV following repeatable vaccinations with a commercial trivalent vaccine (O1, A22, Asia1). Six (10%) bulls were found to possess rather high levels of heterologous neutralizing antibodies which showed accumulative trend with age. Two high positive and two negative bulls for the heterologous serotype C1 were selected for progeny test involving ten daughters of each bull. The four bulls, either positive or negative for the heterologous serotype C1, showed significant phenotypic correlation between their heterologous and homologous titers (O1, A22, Asia1). This correlation between heterologous and homologous antibody titers was not found in the daughters of these bulls. However, two of ten daughters of one positive bull, to C1 showed individual high titers (> or = 1.5). The intradermal (ID) as compared to subcutaneous (SC) route of administration resulted in higher rate of responders to both heterologous serotypes C1 and SAT1. The heterologous immune response to FMDV in Israeli-Friesian cattle was found to be related to the age of the host, multiplicity of vaccinations, route of vaccination, kind and numbers of the antigens used in the vaccine. The homologous immune response is also controlled by genetic factors.

Age Factors↗

PubMed1998

A new approach to the problem of multiple comparisons in the genetic dissection of complex traits.

Saturated genetic marker maps are being used to map individual genes affecting quantitative traits. Controlling the "experimentwise" type-I error severely lowers power to detect segregating loci. For preliminary genome scans, we propose controlling the "false discovery rate," that is, the expected proportion of true null hypotheses within the class of rejected null hypotheses. Examples are given based on a granddaughter design analysis of dairy cattle and simulated backcross populations. By controlling the false discovery rate, power to detect true effects is not dependent on the number of tests performed. If no detectable genes are segregating, controlling the false discovery rate is equivalent to controlling the experimentwise error rate. If quantitative loci are segregating in the population, statistical power is increased as compared to control of the experimentwise type-I error. The difference between the two criteria increases with the increase in the number of false null hypotheses. The false discovery rate can be controlled at the same level whether the complete genome or only part of it has been analyzed. Additional levels of contrasts, such as multiple traits or pedigrees, can be handled without the necessity of a proportional decrease in the critical test probability.

Animals↗

PubMed1998

Estimation of candidate gene effects in dairy cattle populations.

Standard programs for animal models can be modified to include the effect of a candidate gene, even if only a fraction of the population is genotyped. The elements of the incidence matrix for this effect is 0 or 1 for genotyped individuals and for the probabilities of the candidate gene genotypes for individuals that were not genotyped. The effects of a diallelic candidate gene that were estimated by this method were compared on simulated populations with three alternative estimation methods: analysis of genetic evaluations, yield deviations, and daughter yield deviations, all of which were derived from a standard animal model. The bases of comparison were mean squared error and bias. Four types of experimental designs were considered: genotyping sires only, genotyping cows only, genotyping half of the cows but no sires, and genotyping half of the sires and half of the cows. The estimates that were derived from the three alternative methods all underestimated the simulated effects. The genetic evaluations were more biased than were the yield deviations and the daughter yield deviations. The proposed method was significantly biased only for the design in which half of the daughters, but no sires, were genotyped. Bias and mean squared errors were always lowest by the proposed method.

Animals↗

PubMed1997

Genetic analysis of somatic cell score and female fertility of Israeli Holsteins with an individual animal model.

The individual animal model was used to analyze the conception index, defined as the inverse of the number of inseminations to conception, and mean lactation somatic cell scores (SCS) of Israeli Holsteins. In addition, multitrait variance components were estimated for these traits and for milk production traits. The animal model analyses included 440,558 lactation records for conception index and 224,869 SCS records collected over 10 yr. First parity heritabilities were 0.035 for conception index and 0.158 for SCS. Genetic correlations were negative between conception index and milk production traits and positive between SCS and milk production traits. Genetic correlations between first and second lactations were 0.9 for conception index and 0.7 for SCS. Phenotypic correlations were 0.08 and 0.3, respectively. Despite the low heritability for conception index, the standard deviation of the sire evaluations was 2%, and the range of evaluations was 10%. Predicted genetic trends for conception index and SCS were computed based on the current selection index of Israel. The realized genetic trend for the conception index was slightly positive, despite the predicted negative trend, and the realized genetic trend for SCS, although positive as predicted, was fourfold the predicted value. The reasons for these discrepancies are not known.

Animals↗

PubMed1996

Misidentification rate in the Israeli dairy cattle population and its implications for genetic improvement.

The DNA microsatellites can be efficiently used to determine incorrect paternity attribution of cattle without genotyping of dams. Allelic frequencies of the population were determined for 12 microsatellites using the maternal alleles of 102 AI sires. The frequency of the most common microsatellite allele ranged from 0.27 to 0.58. Most loci had at least one allele that was present in only a single individual. Paternity of 9 of 173 cows (5.2%) and 3 of 102 bulls (2.9%) was excluded because putative paternal alleles were not present in progeny for at least one locus. For 4 of the 9 cows and all 3 bulls, exclusion was based on at least two loci. Mean probability of exclusion was 0.85 for cows and 0.99 for bulls. With an assumed cost of US $5 per genotype, a misidentification rate of 5%, and a discount rate of 0.05, additional profit for the Israeli-Holstein breeding program from genotyping 100 test daughters of each young sire becomes positive within 10 yr and reaches nearly US $2.4 million after 20 yr.

Alleles↗

PubMed1996

Effect of season of birth on milk, fat, and protein production of Israeli Holsteins.

The effects of birth month on production of milk, fat, and protein and percentages of fat and protein were analyzed based on production records of 101,653 first parity, 77,541 second parity, and 51,856 third parity Israeli Holstein cows. Each parity was analyzed separately. The analysis model also included the effects of herd-year, DIM, calving age, and calving month. First parity Type III sums of squares for birth month were nearly as large as those for calving month but decreased for later parities. Similar results were obtained using multiplicative models in which the dependent variables were the logarithms of the production traits. The effects of calving month and birth month were not similar, but birth month had similar effects for milk, fat, and protein production. Production was lowest by cows born in the early spring and highest by cows born in the fall. Analyses of the log-transformed traits showed that the F values for calving month were greater than, and the F values for birth month were nearly identical to, the F values for the untransformed trait analyses. The physiological basis for these trends was not clear.

Animals↗

PubMed1995

Methodology and accuracy of estimation of quantitative trait loci parameters in a half-sib design using maximum likelihood.

Maximum likelihood methods were developed for estimation of the six parameters relating to a marker-linked quantitative trait locus (QTL) segregating in a half-sib design, namely the QTL additive effect, the QTL dominance effect, the population mean, recombination between the marker and the QTL, the population frequency of the QTL alleles, and the within-family residual variance. The method was tested on simulated stochastic data with various family structures under two genetic models. A method for predicting the expected value of the likelihood was also derived and used to predict the lower bound sampling errors of the parameter estimates and the correlations between them. It was found that standard errors and confidence intervals were smallest for the population mean and variance, intermediate for QTL effects and allele frequency, and highest for recombination rate. Correlations among standard errors of the parameter estimates were generally low except for a strong negative correlation (r = -0.9) between the QTL's dominance effect and the population mean, and medium positive and negative correlations between the QTL's additive effect and, respectively, recombination rate (r = 0.5) and residual variance (r = -0.6). The implications for experimental design and method of analysis on power and accuracy of marker-QTL linkage experiments were discussed.

Alleles↗

PubMed1995

Prediction of informativeness for microsatellite markers among progeny of sires used for detection of economic trait loci in dairy cattle.

Individual loci affecting economic traits can be located using genetic linkage. Application of either daughter or granddaughter design requires determination of allele origin in the progeny. If only the sires and their progeny are genotyped, the paternal allele origin of progeny having the same genotype as the sire cannot be determined. The expected frequency of informative sons can be predicted for each sire and genetic marker from the allele frequencies in the population. The accuracy of a predictor of the frequency of informative progeny was tested on 103 grandsire x microsatellite combinations. Number of sons per grandsire varied from 24 to 129. Allele frequencies in the population were estimated by genotyping seven sires. The regression of the frequency of informative sons on the predicted frequency was 1.04 with a zero intercept model. Thus, considering the large number of genetic markers available for analysis, predicted informative frequency is a useful criterion for selection of genetic markers.

Animals↗

PubMed1995

Genetic mapping of quantitative trait loci for traits with ordinal distributions.

Statistical methods for mapping quantitative trait loci relative to genetic markers are now well established for continuous traits with normal distributions. However, many traits of economic importance are recorded on a discrete, ordinal scale. Here we describe a model developed for the analysis of ordinal traits, such as degree of difficulty in calving or categories of plant disease resistance. The model estimates the distance from the quantitative trait locus to neighbouring genetic markers, and also genetic parameters, either as gene effects on an underlying continuous scale or as probabilities of the observed categories. The model is tested on simulated data and is compared with an analysis based on mixtures of normal distributions. The ordinal model is found to estimate the parameters more accurately, especially when the number of categories is small or when only one linked marker is available.

Animal Husbandry↗

PubMed1994

An enrichment object that reduces aggressiveness and mortality in caged laying hens.

The effect on aggressive pecking activity and mortality by an environmental enrichment device was examined. In this study, 2955 White Leghorn chickens from three different lines were used in six separate experiments. Experiments were conducted with chickens during their first or second laying period. Half the cages in each experiment were equipped with colored key rings or an enrichment object manufactured by Gallus Ltd. (Israel). Experimental and control groups of cages were distributed in an alternate serial order for each experiment which lasted for 3, 4, 5, 8, 9, and 10 months. The enrichment devices significantly reduced aggressive head-pecking behavior and significantly decreased the mortality rate from 1.06% per month among the controls to 0.57% among the experimental groups.

Aggression↗

PubMed1994

Maximum likelihood estimation of quantitative trait loci parameters with the aid of genetic markers using a standard statistical package.

Consistent parameter estimates of quantitative trait loci linked to genetic markers can be derived by maximum likelihood methodology. For many experimental designs of interest, parameter estimates and their standard errors can be obtained by program LE of BMDP, which uses the Newton-Raphson method of iteration. Program LE was tested on data simulated for a backcross between two inbred lines. A single quantitative trait locus linked to either one or two genetic markers was simulated. Convergence was rapid, and computing and programming time were insignificant. All parameter estimates were within the expected bounds. Many different designs can be readily analyzed.

Algorithms↗

PubMed1994

Mapping and analysis of dairy cattle quantitative trait loci by maximum likelihood methodology using milk protein genes as genetic markers.

Maximum likelihood methodology was used to estimate effects of both a marker gene and a linked quantitative trait locus (QTL) on quantitative traits in a segregating population. Two alleles were assumed for the QTL. In addition to the effects of genotypes at both loci on the mean of the quantitative trait, recombination frequency between the loci, frequency of the QTL alleles and the residual standard deviation were also estimated. Thus six parameters were estimated in addition to the marker genotype means. The statistical model was tested on simulated data, and used to estimate direct and linked effects of the milk protein genes, beta-lactoglobulin, kappa-casein, and beta-casein, on milk, fat, and protein production and fat and protein percent in the Dutch dairy cattle population. beta-Lactoglobulin had significant direct effects on milk yield and fat percent. kappa-Casein had significant direct effects on milk yield, protein percent and fat yield. beta-Casein had significant direct effects on milk yield, fat and protein percent and fat and protein yield. Linked QTL with significant effects on fat percent were found for kappa-casein and beta-casein. Since the beta-casein and kappa-casein genes are closely linked, it is likely that the same QTL was detected for those two markers. Further, a QTL with a significant effect on fat yield was found to be linked to kappa-casein and a QTL with a significant effect on protein yield was linked to beta-lactoglobulin.

Alleles↗

PubMed1994

Mapping quantitative trait loci with DNA microsatellites in a commercial dairy cattle population.

Individual loci affecting economically important traits can be located using genetic linkage between quantitative trait loci and genetic markers. In the 'granddaughter' experimental design, heterozygous grandsires and their sons are genotyped for the genetic marker, while the quantitative trait records of the granddaughters are used for statistical analysis. Ten DNA microsatellite markers were used to look for associations with quantitative trait loci affecting milk production traits in seven Israeli Holstein grandsire families. At least 60% more grandsires were heterozygous, and 40% fewer individuals were discarded because of unknown paternal allele origin, as compared with diallelic markers. The effects of paternal alleles for locus D21S4 on kg milk and protein were significant (P < 0.025). The allele substitution effects for sire 783 were 283 kg milk and 5.7 kg protein. For both traits, progeny of sire 783 that inherited allele '18' had higher evaluations than progeny that inherited allele '21'. These results were verified by genotyping 151 of his daughters. Thus, the rate of genetic gain for protein production can be increased by selecting progeny of sire 783 carrying allele '18' at this locus.

Animals↗

PubMed1994

Determination of effects of milk protein genotype on production traits of Israeli Holsteins.

Genotypes of 112 Israeli Holstein sires were determined for beta-lactoglobulin and kappa-casein by restriction fragment length polymorphism analysis of amplified DNA. Frequencies of the A alleles were .89 and .52 for kappa-casein and beta-lactoglobulin, respectively. Genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Two models were used to test the effect of these loci on production of milk, fat, and protein and on fat and protein percentages. The dependent variable in the first model was production of 84,593 daughters of 110 genotyped sires, and the independent variables were herd-year-season, sire genotype for beta-lactoglobulin and kappa-casein, the interaction of the two loci, and sire nested within genotype. In the second model, the dependent variable was individual animal model genetic evaluations of 111 sires for production traits, and milk protein genotypes were the independent variables. The only significant effect of genotype with both models was the interaction of the two loci on fat percentage. When sires, rather than cows, were genotyped, the contrasted groups differed by only one-half of the genotype effect, but the residual variance was reduced.

Alleles↗

PubMed1994

A simple procedure for obtaining approximate interim cow solutions from an animal model.

The computational costs required for solving the equations for an individual animal mixed model can be considerable. More frequent evaluations would benefit dairy producers, allowing them to make breeding and management decisions earlier. A procedure was developed to immediately obtain approximate estimates of cow breeding value as soon as new information becomes available. Only solutions for cows with records in progress are updated. The algorithm is based on solving a system of two equations and can be applied by producers. The method corrects for changes in estimated production of the current record of a cow but assumes that the effects of changes in evaluations of other animals related to this cow on the evaluation of the cow in question are negligible. Herd-year-season effects are not reestimated. The correlations between the updated cow evaluations based on animal model evaluations computed during May 1992, but using estimated production from November 1992, for records in progress and the animal model evaluations from November were .027 to .064 higher than the correlations between the May and November evaluations for production of milk, fat, and protein. Although gains are slight, the cost application of the algorithm is insignificant.

Algorithms↗

PubMed1993

Detecting marker-QTL linkage and estimating QTL gene effect and map location using a saturated genetic map.

A simulation study was carried out on a backcross population in order to determine the effect of marker spacing, gene effect and population size on the power of marker-quantitative trait loci (QTL) linkage experiments and on the standard error of maximum likelihood estimates (MLE) of QTL gene effect and map location. Power of detecting a QTL was virtually the same for a marker spacing of 10 cM as for an infinite number of markers and was only slightly decreased for marker spacing of 20 or even 50 cM. The advantage of using interval mapping as compared to single-marker analysis was slight. "Resolving power" of a marker-QTL linkage experiment was defined as the 95% confidence interval for the QTL map location that would be obtained when scoring an infinite number of markers. It was found that reducing marker spacing below the resolving power did not add appreciably to narrowing the confidence interval. Thus, the 95% confidence interval with infinite markers sets the useful marker spacing for estimating QTL map location for a given population size and estimated gene effect.

Chromosome Mapping↗

PubMed1993

Unequivocal determination of sire allele origin for multiallelic microsatellites when only the sire and progeny are genotyped.

The effect of a segregating economic trait locus (ETL) can be detected with the aid of a linked genetic marker, if specific alleles of each locus are in association among the individuals genotyped for the genetic marker. For dairy cattle this can be achieved by application of the 'granddaughter design'. If only the sires and their sons are genotyped for the genetic markers, then the allele origin of sons having the same genotypes as their sires cannot be determined. Seven sires and 101 sons were genotyped for five microsatellites. The mean frequency of heterozygous sires was 77%. The mean number of alleles per locus was 8.2. Frequency of informative sons per locus ranged from 60% to 80% with a mean of 72%. With highly polymorphic microsatellites, at least 60% more grandsire families can be included in the analysis, and the number of sons assayed can be reduced by 40%, as compared to diallelic markers.

Alleles↗

PubMed1993

Sequence variation in D-loop mtDNA of cow lineages selected for high and low maternal effects on milk production.

The four highest and four lowest cow lineages for milk production were selected from 324 maternal lineages of the Israeli Holstein population. For a single cow from each lineage, the mitochondrial D-loop region was amplified using the polymerase chain reaction and directly sequenced for 719bp. Eighteen polymorphic sites were found of which 17 were substitutions and one was an insertion. Only two alleles were found for each polymorphic site, one of which corresponded to the sequence of Anderson et al. (1982), which was the more frequent allele, in all but two sites. None of the polymorphic sites had an apparent effect on milk production, even though an effect > or = 0.33 phenotypic standard deviations, equivalent to 470 kg milk, could be detected by this experimental design. Furthermore, there was no indication that moderately increasing the sample size would have altered the result, since all rare alleles found in more than a single lineage were found in both the high and low subgroups.

Animals↗