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Identification of an ovulation rate QTL in cattle on BTA14 using selective DNA pooling and interval mapping.

Increased twinning incidence in beef cattle has the potential to improve production efficiency. However, phenotypic selection for twinning rate is difficult because of the trait's low heritability and the long time interval necessary to collect phenotypic records. Therefore, this trait and the correlated trait of ovulation rate are ideal candidates for marker-assisted selection. The objective of this study was to complete a genome-wide search for ovulation rate quantitative trait loci (QTL) in two related sire families. The families (paternal halfsib sires 839802 and 839803) were from a population of cattle selected for ovulation rate at the USDA Meat Animal Research Center, Clay Center, Nebraska. Putative ovulation rate QTL have previously been identified in the 839802 family on chromosomes 7 and 19; however, marker coverage in the original scan was not complete. This study fills the gaps in marker coverage of the earlier study by adding approximately 60 informative microsatellites to each sire family. Each family was genotyped using selective DNA pooling. Sons and daughters were included in either the high or low pool based on their estimated breeding value deviations from the mid-parent average (EBVMD) for ovulation rate. Approximately 40% (839802) and 26% (839803) of available progeny comprised the high and low pools combined. Pooled typing revealed possible associations (nominal P < 0.05) between ovulation rate and marker genotype for 11 and 15 microsatellites in the 839802 and 839803 families, respectively. Subsequent interval mapping strengthened support for the presence of an ovulation rate QTL on BTA14 (chromosome-wise P < 0.02).

Animals↗

Association of the heart fatty acid-binding protein (FABP3) gene with milk traits in Manchega breed sheep.

The ovine fatty acid-binding protein type 3 gene has been chosen as a functional candidate gene for milk traits. Two different single nucleotide polymorphisms (SNPs) of ovine FABP3 gene have been tested in a daughter design comprising 13 families. No association was found between estimated breeding values for milk yield, protein and fat contents (FC) and genotypes across families using anova and transmission disequilibrium test (TDT). In within-family analysis, one family showed a significant effect for FC. These results could indicate linkage disequilibrium between the FABP3 gene and a quantitative trait loci (QTL) for FC, with the heterozygous genotype associated with a positive effect in this trait.

Analysis of Variance↗

The effects of selection for size in cattle on horn fly population density.

Statistically significant differences were observed in the population density of the horn fly, Haematobia irritans irritans L., on Angus cows having significantly different frame sizes. Angus cows, averaging < 112.5 cm in height at the hip, had significantly lower numbers of horn flies than Angus cows that measured 112.5-117.5 cm, 117.5-120 cm, 120-126 cm and > 126 cm in height at the hip. The Angus I cows ( < 112.5 cm in height at the hip) were significantly shorter in length (mean distance from the withers to the hip bone) and were smaller in girth than the Angus II (112.5-126 cm) and Booneville Angus cows ( > 126 cm). The estimated heritability (h2) of horn fly resistance was 0.43 +/- 0.07 and 0.95 +/- 0.31 for 1989 and 1990, respectively. Horn fly counts on the Angus I herd ( < 112.5 cm in height) was 118.1 (probable breeding value, PBV = -20.69) to 165 horn flies per cow (PBV = 26.9 flies per cow in 1989) and from 75.9 (PBV = -29.1) to 134.5 (PBV = 29.5) flies per cow in 1990. Angus I bulls had PBV = -23.7 to 13.4 and from -26.5 to 14.75 in 1989 and 1990, respectively. The Angus II cows had horn fly counts that ranged from 159.6 (PBV of -23.5) to 208.1 (PBV of 25) per cow in 1989 and from 232.3 (PBV of -56.2) to 378.7 (PBV of 90) per cow in 1990. Angus II bulls had PBVs that ranged from -17.1 to 18.9 in 1989 and from -28.1 to 48.8 in 1990. The Angus I cows had significantly (P < 0.0001) lower numbers of horn flies (mean of 63.8 horn flies per m2) than the small, medium or large Angus II cows (mean of 129.4, 149.6 and 145.5 horn flies per m2, respectively). The data indicated that some specific factor(s) associated with cow size contribute(s) to innate resistance of cattle to the horn fly.

Animals↗

Maize association population: a high-resolution platform for quantitative trait locus dissection.

Crop improvement and the dissection of complex genetic traits require germplasm diversity. Although this necessary phenotypic variability exists in diverse maize, most research is conducted using a small subset of inbred lines. An association population of 302 lines is now available--a valuable research tool that captures a large proportion of the alleles in cultivated maize. Provided that appropriate statistical models correcting for population structure are included, this tool can be used in association analyses to provide high-resolution evaluation of multiple alleles. This study describes the population structure of the 302 lines, and investigates the relationship between population structure and various measures of phenotypic and breeding value. On average, our estimates of population structure account for 9.3% of phenotypic variation, roughly equivalent to a major quantitative trait locus (QTL), with a high of 35%. Inclusion of population structure in association models is critical to meaningful analyses. This new association population has the potential to identify QTL with small effects, which will aid in dissecting complex traits and in planning future projects to exploit the rich diversity present in maize.

Chromosome Mapping↗

Characterization of a line of pigs previously selected for increased litter size for RBP4 and follistatin.

The objective of this study was to determine if selection response for increased litter size in pigs could be partially attributed to three type 1 marker loci coding for genes known to affect litter size: oestrogen receptor (ESR), retinol-binding protein 4 (RBP4) and follistatin (FS). In the high litter size line (LS), pigs from the largest litters, based on number of pigs born alive (NBA), were retained to parent the next generation. A randomly selected control line (LC) was maintained. Gilts were reared in litters of 10 pigs or less to minimize maternal effects. Pigs were measured at generations 10-12. Additional traits scored were number of fully formed pigs (NFF) and number of mummified fetuses (MUM). Breeding values for NFF and NBA were greater (p < 0.05) in LS than LC in generations 11 and 12, but no significant line differences were found for MUM. The A allele of the ESR locus was fixed in both lines. After adjustment for effects of genetic drift, frequency of the two alleles segregating for the FS and RBP4 loci did not differ significantly between lines. No significant additive or dominance effects of the FS markers were detected for NFF, NBA and MUM in either LS or LC. Response to selection for increased litter size could not be attributed to effects at the ESR, RBP4 or FS loci.

Animals↗

The effect of parentage on the prevalence, severity and location of lesions of osteochondrosis in swine.

The aims of this study were to determine the effects of parentage and gender on the prevalence, severity and location of lesions of osteochondrosis manifesta (OCM) and osteochondrosis dissecans (OCD) in offspring from different Norwegian Landrace boars and to examine the relationships between lesion characteristics and selected growth parameters. Fifteen sires were selected based on their high breeding value for osteochondrosis. Seven locations in the distal humerus and the distal femur from 1680 offspring of these animals were evaluated for severity of OCM and presence of OCD by gross examination of serially sectioned humeri and femora. Osteochondrosis manifesta was most prevalent in the trochlea of humerus, the sagittal ridge of humerus, the medial condyle of femur and the medial sulcus obliquus of femur. The severity of the lesions and the prevalence of OCD were highest in the trochlea and the sagittal ridge of humerus. Castrates had significantly higher OCM scores than sows. There were significant effects of both sire and dam on the OCM scores of the offspring in most locations; however, growth rate and weight at slaughter did not influence the OCM score.

Animals↗

Genetic evaluation of elbow angles as predictors of elbow dysplasia in German shepherd dogs.

Elbow angles were measured in X-rays of both elbows to elucidate the usefulness of such data for selecting against elbow dysplasia (ED) in German shepherd dogs. These measurements record the size, proportions and alignments of the anconeal process (PA), the radius (RA), the olecranon (OL), and the ulnar trochlear notch (UL). The reference system for evaluating the information content of the measurements was the score for ED (ED-SV) as recommended by the International Elbow Working Group. Data from 2645 X-rayed dogs born from 1998 to 2001 in 1331 kennels were analysed by using residual maximum likelihood procedures to estimate heritabilities, additive genetic correlations and residual correlations. The pedigree file included 11,426 dogs and contained ancestors for up to six generations. ED-SV was significantly influenced by sex, by age within sex and by month of birth. The elbow angles were significantly influenced by the month and year of birth, X-ray positioning of the dog's forelimbs, angle of elbow flection, litter size and number of dogs X-rayed by the veterinary practitioners. The following heritability estimates were found: h2=0.18+/-0.04 for ED; h2=0.76+/-0.04 for OL; h2=0.52+/-0.05 for PA; h2=0.50+/-0.04 for UL; and h2=0.39+/-0.04 for RA. The additive genetic correlations of ED-SV with three elbow angles (OL, UL and RA) were close to zero. A higher additive genetic correlation to ED-SV was found only for PA, for which r(g)=0.31. The distributions of predicted breeding values for susceptibility to ED were not affected by regarding the elbow angles as additional traits in the multivariate prediction procedure. Measurements of elbow angles were thus shown to be unsuitable for use in selection programmes against ED in German shepherd dogs.

Animals↗

Establishment of a pregnancy following intravaginal insemination with epididymal semen from a dog castrated due to benign prostatic hyperplasia.

Benign prostatic hyperplasia was diagnosed in an American Staffordshire Terrier of high breeding value presenting concurrent haematuria. Castration as a treatment was synchronized with the oestrus cycle of a bitch selected for insemination. After castration the cauda epididymis was flushed with Gent semen extender and collected spermatozoa were filtered and analysed by Hamilton Thorn computer assisted sperm analysis. A total of 7 ml semen containing 742 x 10(6) spermatozoa with 76.5% mean motility was used for insemination. Intravaginal insemination of the bitch was performed with an insemination catheter for dogs (Kruuse, Marslev, Denmark) on the day when plasma progesterone levels reached 9.9 ng/ml. Normal pregnancy without complications resulted in eight live-born puppies 63 days after insemination. This is the first report of a normal pregnancy and birth of puppies from a bitch inseminated with epididymal semen obtained from a dog affected by benign prostate hyperplasia.

Animals↗

Genetic analysis of three different classification protocols for the evaluation of elbow dysplasia in German shepherd dogs.

OBJECTIVES: Three different scoring systems for elbow dysplasia and its radiographic signs were genetically evaluated in 2645 German shepherd dogs. METHODS: An animal model was used to estimate heritabilities and additive genetic and residual correlations for the three scoring systems: ED-SV, which is recommended by the International Elbow Working Group; ED-LA, developed by Lang and others; and ED-TH, proposed by Tellhelm. RESULTS: The effects of sex, age at examination and the correlation between the two factors were significant for all three scoring systems. Heritability estimates (se) were 0.18 (0.04) for ED-SV, 0.11 (0.03) for ED-LA and 0.16 (0.04) for ED-TH. The additive genetic correlations among the different single criteria for elbow dysplasia and the different elbow dysplasia scores were between 0.68 and 0.98, except for the criteria ununited anconeal process and osteochondrosis dissecans of the trochlea humeri, which were mostly genetically negatively correlated to the other radiological criteria. CLINICAL SIGNIFICANCE: The elbow dysplasia scores were determined by two genetically different traits. The possibilities for selecting German shepherd dogs with respect to elbow dysplasia might be improved by taking into account these two traits in the prediction of breeding values.

Age Factors↗

Estimation of the heritability of lameness in standardbred trotters.

The degree of lameness of 265 randomly selected three-year-old standardbred trotters was assessed on a fixed point scale with 0 indicating soundness and 5 indicating that the animals were not weightbearing. Two variables were used to describe the signs of lameness; one was the continuous variable: the sum of the initial lameness score and the lameness scores after separate flexion tests of the carpal, stifle/tarsal and phalangeal joints and the second was the bivariate variable; the ratio of lame/sound horses. The mean (sd) heritability of the continuous variable was estimated to be 0.25 (0.21), and the model was significant (P = 0.05) with a determination coefficient of R2 = 0.14. For the bivariate variable, lame/sound, the heritability was estimated to be 0.33. The breeding values for the 16 sires in the analyses ranged from 72.2 to 130.5. No influence of gender on the prevalence of lameness was detected.

Animals↗

Genetic variability in melatonin concentrations in ewes originates in its synthesis, not in its catabolism.

We investigated whether the genetic difference in plasma melatonin concentration in ewes was due to differences in the synthesis pathway from the pineal gland or in the catabolism of the hormone. Two groups of ewes [9 low (L) and 10 high (H)] were selected according to the breeding value of their mean nighttime plasma melatonin concentrations estimated at winter and summer solstices. In response to an identical dose of melatonin administered intravenously at 9:00 AM, no differences between groups were observed for any of the kinetic parameters: clearance rate, steady-state volume of distribution, terminal half-lives, and mean residence times. In the second experiment, two series of frequent blood samples were performed, one in the middle of the dark phase with samples taken every 5 min, and the other over 24 h with hourly samples. Highly significant differences between groups in nocturnal melatonin production rate were observed (L: 25.7 +/- 2.8 vs. H: 63.1 +/- 8.9 microg . kg-1 . h-1, P < 0.01). Thus the genetic differences in plasma melatonin concentrations in ewes originate in the synthesis pathway of the melatonin from the pineal gland rather than from differences in the catabolism of the hormone.

Animals↗

A rapid method for computing the inverse of the gametic covariance matrix between relatives for a marked quantitative trait locus.

The inverse of the gametic covariance matrix between relatives, G(-1), for a marked quantitative trait locus (QTL) is required in best linear unbiased prediction (BLUP) of breeding values if marker data are available on a QTL. A rapid method for computing the inverse of a gametic relationship matrix for a marked QTL without building G itself is presented. The algorithm is particularly useful due to the approach taken in computing inbreeding coefficients by having to compute only few elements of G. Numerical techniques for determining, storing, and computing the required elements of G and the nonzero elements of the inverse are discussed. We show that the subset of G required for computing the inbreeding coefficients and hence the inverse is a tiny proportion of the whole matrix and can be easily stored in computer memory using sparse matrix storage techniques. We also introduce an algorithm to determine the maximum set of nonzero elements that can be found in G(-1) and a strategy to efficiently store and access them. Finally, we demonstrate that the inverse can be efficiently built using the present techniques for very large and inbred populations.

Algorithms↗

Selection against genetic defects in conservation schemes while controlling inbreeding.

We studied different genetic models and evaluation systems to select against a genetic disease with additive, recessive or polygenic inheritance in genetic conservation schemes. When using optimum contribution selection with a restriction on the rate of inbreeding (DeltaF) to select against a disease allele, selection directly on DNA-genotypes is, as expected, the most efficient strategy. Selection for BLUP or segregation analysis breeding value estimates both need 1-2 generations more to halve the frequency of the disease allele, while these methods do not require knowledge of the disease mutation at the DNA level. BLUP and segregation analysis methods were equally efficient when selecting against a disease with single gene or complex polygene inheritance, i.e. knowledge about the mode of inheritance of the disease was not needed for efficient selection against the disease. Smaller schemes or schemes with a more stringent restriction on DeltaF needed more generations to halve the frequency of the disease alleles or the fraction of diseased animals. Optimum contribution selection maintained DeltaF at its predefined level, even when selection of females was at random. It is argued that in the investigated small conservation schemes with selection against a genetic defect, control of DeltaF is very important.

Animals↗

Full conjugate analysis of normal multiple traits with missing records using a generalized inverted Wishart distribution.

A Markov chain Monte Carlo (MCMC) algorithm to sample an exchangeable covariance matrix, such as the one of the error terms (R0) in a multiple trait animal model with missing records under normal-inverted Wishart priors is presented. The algorithm (FCG) is based on a conjugate form of the inverted Wishart density that avoids sampling the missing error terms. Normal prior densities are assumed for the 'fixed' effects and breeding values, whereas the covariance matrices are assumed to follow inverted Wishart distributions. The inverted Wishart prior for the environmental covariance matrix is a product density of all patterns of missing data. The resulting MCMC scheme eliminates the correlation between the sampled missing residuals and the sampled R0, which in turn has the effect of decreasing the total amount of samples needed to reach convergence. The use of the FCG algorithm in a multiple trait data set with an extreme pattern of missing records produced a dramatic reduction in the size of the autocorrelations among samples for all lags from 1 to 50, and this increased the effective sample size from 2.5 to 7 times and reduced the number of samples needed to attain convergence, when compared with the 'data augmentation' algorithm.

Algorithms↗

Identification of gametes and treatment of linear dependencies in the gametic QTL-relationship matrix and its inverse.

The estimation of gametic effects via marker-assisted BLUP requires the inverse of the conditional gametic relationship matrix G. Both gametes of each animal can either be identified (distinguished) by markers or by parental origin. By example, it was shown that the conditional gametic relationship matrix is not unique but depends on the mode of gamete identification. The sum of both gametic effects of each animal--and therefore its estimated breeding value--remains however unaffected. A previously known algorithm for setting up the inverse of G was generalized in order to eliminate the dependencies between columns and rows of G. In the presence of dependencies the rank of G also depends on the mode of gamete identification. A unique transformation of estimates of QTL genotypic effects into QTL gametic effects was proven to be impossible. The properties of both modes of gamete identification in the fields of application are discussed.

Algorithms↗

Parallel computations on pedigree data through mapping to configurable computing devices.

Pedigree data structures have a number of applications in genetics, including the estimation of allelic or haplotype probabilities in humans and agricultural species, and the estimation of breeding values in agricultural species. Sequential algorithms for general purpose CPU-based computers are commonly used, but are inadequate for some tasks on large data sets. We show that pedigree data can be directly represented on Field Programmable Gate Arrays (FPGA), allowing highly efficient massively parallel simulation of the flow of genes. Operating on the whole pedigree in parallel, the transmission of genes can occur for all individuals in a single clock cycle. By using FPGA, the algorithms to estimate inbreeding coefficients and allelic probabilities are shown to operate hundreds to thousands of times faster than the corresponding sequentially based algorithms. Where problems can be largely represented in an integer form, FPGA provide an efficient platform for computations on pedigree data.

Algorithms↗

Effects of complex vertebral malformation on fertility in Swedish holstein cattle.

Complex vertebral malformation (CVM) is an autosomal recessive inherited defect in the Holstein breed. It causes intra-uterine mortality through the entire gestation period leading to repeat breeding and involuntary culling of cows and thereby economic losses. The defect was first reported in Denmark in 1999 and a direct DNA test for the defect has been available since February 2001. The aim of this study was to investigate if Holstein bulls heterozygous for the CVM gene had reduced reproductive performance, measured as non-return rate (NRR) and in a daughter fertility index. All genotyped Swedish Holstein bulls born between 1995 and 1999 were included. Altogether 228 bulls were analysed, of which 53 bulls, i.e. 23%, were confirmed CVM carriers. A statistically significant difference between carriers and non-carriers in the relative breeding value for NRR was observed for 168 days NRR (101.1+/-0.9 vs. 103.1+/-0.6, p<0.05). There was no difference for 28 days NRR whereas the difference approached significance for 56 days NRR. No significant effect of the paternal CVM genotype on the daughter fertility index was shown probably due to the complexity of traits this index is composed of. In conclusion, the study showed that carriers of the CVM defect have an inferior NRR compared with non-carriers.

Abnormalities, Multiple↗

Endocrine profiles, haematology and pregnancy outcomes of late pregnant Holstein dairy heifers sired by bulls giving a high or low incidence of stillbirth.

The high incidence of stillbirth in Swedish Holstein heifers has increased continuously during the last 15 years to an average of 11% today. The pathological reasons behind the increased incidence of stillbirth are unknown. The present experiment was undertaken to investigate possible causes of stillbirth and to study possible physiological markers for predicting stillbirth. Twenty Swedish Holstein dairy heifers sired by bulls with breeding values for a high risk of stillbirth (n = 12) (experimental group) and a low risk of stillbirth (n = 8) (control group, group B) were selected based on information in the Swedish AI-data base. The experimental group consisted of 2 subgroups of heifers (groups A1 and A2) inseminated with 2 different bulls with 3.5% and 9% higher stillbirth rates than the average, and the control group consisted of heifers pregnant with 5 different bulls with 0%-6% lower stillbirth rates than the average. The bull used for group A1 had also calving difficulties due to large calves as compared to the bull in group A2 showing no calving difficulties. The heifers were supervised from 6-7 months of pregnancy up to birth, and the pregnancies and parturitions were compared between groups regarding hormonal levels, haematology, placental characteristics and calf viability. In group A1, 1 stillborn, 1 weak and 4 normal calves were recorded. In group A2, 2 stillborn and 4 normal calves were registered. All animals in the control group gave birth to a normal living calf without any assistance. The weak calf showed deviating profiles of body temperature, saturated oxygen and heart rates, compared with the normal living calves. No differences of the placentome thickness, measured in vivo by ultrasonography were seen between the groups. The number of leukocytes and differential cell counts in groups A1 and A2 followed the profiles found in the control group. In group A1, a slight decrease of oestrone sulphate (E1SO4) levels was found in the animal delivering a stillborn calf from the first 24-h blood sampling at 6 weeks to the second at 3 weeks prior to delivery, while the levels of E1SO4 at both periods in the animal delivering a weak calf followed the profile in animals delivering a normal living calf. During late pregnancy and at the time of parturition, the levels of E1SO4 and PAGs in animals delivering a stillborn or weak calf (from group A1) followed the normal profiles found in animals delivering a normal living calf. In group A2, low levels of E1SO4 and pregnancy associated glycoproteins (PAGs) over 24 h at both 3 and 6 weeks prior to parturition (< 1.5 nmol/L) were recorded in animals delivering a stillborn calf. During late pregnancy and parturition, the levels of E1SO4 and PAGs were slightly lower during 30-50 days prior to delivery and increased with a lower magnitude at the time of parturition. In conclusion, our results indicate that the aetiology behind stillbirth varies depending on the AI-bulls used and is associated with dystocia or low viability of the calves. Deviating profiles of oestrone sulphate (E1SO4) and pregnancy associated glycoproteins (PAGs) in animals delivering a stillborn calf not caused by dystocia were observed, suggesting placental dysfunction as a possible factor. The finding suggests that the analyses of E1SO4 and PAGs could be used for monitoring foetal well-being in animals with a high risk of stillbirth at term.

Animals↗