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1.
J Dairy Sci ; 104(9): 10020-10028, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34147222

ABSTRACT

Compared with cow fertility, genetic analyses of bull fertility are limited and based on relatively few animals. The aim of the present study was to estimate genetic parameters for semen characteristics of Norwegian Red bulls at the artificial insemination (AI) center (Geno AI station, Stange, Norway) and to estimate genetic correlations between some of these traits and andrology traits measured at the performance test station. The data from the AI center consisted of records from 137,919 semen collections from 3,145 bulls with information on semen weight, sperm concentration, motility before and after cryopreservation, motility change during cryopreservation, and number of accepted straws made. Data from the performance test station included 12,522 observations from 3,219 bulls on semen volume, concentration, and motility (%) when fresh and after storing for 24 and 48 h. Genetic parameters were estimated using linear animal repeatability models that included fixed effects of year-month of observation, age of bull, interaction between semen collection number, and interval between collections for all traits and type of diluter for postcryopreservation traits. The random effects included test-day, permanent environmental, and additive genetic effects of the bull. Based on records from the AI center, we found that semen weight, sperm concentration, and number of straws were moderately heritable (0.18-0.20), whereas motility had a lower heritability (0.02-0.08). Heritability of motility (%) was higher after cryopreservation than before. Genetic correlations among the semen characteristics ranged from unfavorable (-0.35) to favorable (0.93), with standard errors ranging from 0.02 to 0.22. Among the most precise genetic correlation estimates, number of straws made from a batch correlated favorably with semen weight (0.62 ± 0.06) and sperm concentration (0.44 ± 0.08), whereas sperm concentration was negatively correlated with weight (-0.33 ± 0.09). The genetic correlation between motility (%) before and after cryopreservation was 0.64 ± 0.14, and motility change during cryopreservation had a strong favorable genetic correlation with motility after cryopreservation (-0.93 ± 0.02). The estimated genetic correlation (standard error) between the traits volume, concentration, and motility when fresh measured at the performance test station and their respective corresponding traits at the AI center were 0.83 (0.05), 0.78 (0.09), and 0.49 (0.31). The final product at the AI center (number of accepted straws) correlated genetically favorably with all semen characteristic traits recorded at the performance test station (ranging from 0.51 to 0.67). Our results show that the andrology testing done at the performance test station is a resource to identify the genetically best bulls for AI production.


Subject(s)
Semen Preservation , Semen , Animals , Cattle/genetics , Cryopreservation/veterinary , Female , Insemination, Artificial/veterinary , Male , Semen Analysis/veterinary , Semen Preservation/veterinary , Sperm Motility/genetics , Spermatozoa
2.
J Dairy Sci ; 103(7): 6311-6317, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32389477

ABSTRACT

The aim of this study was to estimate genetic parameters for body weight (BW) at 150 d (Bw_150d), and 330 d (Bw_330d) of age and average daily weight gain (Dwg), and to estimate genetic correlations between these traits and semen characteristic traits: volume; concentration (Conc); motility in fresh, 24-h, and 48-h samples (Mot0h, Mot24h, Mot48h); and sperm defects. Data were collected at the performance test station of young Norwegian Red bulls from 2002 to 2012, before selection of bulls for artificial insemination. The weight and growth data consisted of observations for 3,209 bulls, and andrology information was available for up to 2,034 of these bulls. Genetic parameters were estimated using linear animal models. Models for BW and growth traits included the group and year the bull left the station and the pen they occupied during weighing (group-year-pen) and parity of their dam as fixed effects. Models for andrology traits had group-year, age in months (11 to 15), and the interaction between ejaculate number and days since previous collection included as fixed effects. Estimated heritability was 0.14 for Bw_150d, 0.26 for Bw_330d, and 0.34 for Dwg; the estimated genetic correlations among these traits were all favorable. Both BW traits correlated favorably with all the semen characteristic traits (0.20 to 0.76), whereas Dwg was favorably correlated with volume, Mot24h, Mot48h, and sperm defects, and unfavorably correlated with Conc (-0.25) and Mot0h (-0.53). Our results indicate that the genetic correlations between weight and growth traits and semen characteristics depend on the age of the bulls. Although most genetic correlations were favorable, selection for higher daily weight gain between 150 and 330 d might explain the slight negative genetic trends observed for semen characteristics in young Norwegian Red bulls.


Subject(s)
Body Weight , Cattle/physiology , Semen , Weight Gain , Animals , Cattle/genetics , Cattle/growth & development , Female , Insemination, Artificial , Linear Models , Male , Norway , Parity , Phenotype , Pregnancy , Selective Breeding , Sperm Motility , Spermatozoa
3.
J Dairy Sci ; 103(1): 545-555, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31668445

ABSTRACT

The aim of this study was to estimate genetic parameters and genetic trends for male fertility in Norwegian Red bulls. We analyzed data on semen characteristics traits collected at the performance test station of young bulls from 1994 to 2016, in an andrology test used to ensure acceptable semen quality before being selected as an artificial insemination bull. Traits included were volume, concentration, and motility (percentage of moving sperm cells) in fresh samples and after storing for 24 and 48 h, and sperm defects. The data consisted of 14,972 ejaculates from 3,927 young (11-15 mo) Norwegian Red bulls. Genetic parameters were estimated using bivariate linear animal models that included age in months, group-year, and collection-group (main effect of the interaction between ejaculate number and interval between collections) as fixed effects, and test-day and additive genetic and permanent environment effect of the bull as random effects. Considerable genetic coefficients of variation were found for concentration and volume, with lower values for motility. Estimated heritabilities ranged from 0.02 and 0.03 (for sperm defects and motility in fresh samples) to 0.14 (volume and concentration measured on a continuous scale). All estimated genetic correlations were favorable, but the genetic correlations between volume and concentration and volume and sperm defects were not significantly different from zero. The genetic correlations between concentration and motility traits ranged from 0.53 to 0.83, and those between volume and the motility traits were between 0.24 and 0.57. All traits showed a slightly unfavorable genetic trend. Our results indicate that selection of bulls with better sperm quality is possible.


Subject(s)
Cattle/genetics , Semen Analysis/veterinary , Semen , Animals , Insemination, Artificial/veterinary , Male , Norway , Sperm Motility , Spermatozoa
4.
J Pediatr Urol ; 15(4): 322-329, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31227314

ABSTRACT

The investigation, management and follow-up of paediatric ureteropelvic junction obstruction is not standardized. The Young Pediatric Urology Committee of the European Society of Pediatric Urology interviewed five experts in the field on various aspects of management and compared this with published literature.


Subject(s)
Disease Management , Laparoscopy/methods , Plastic Surgery Procedures/methods , Ureteral Obstruction/surgery , Urologic Surgical Procedures/methods , Child , Humans , Kidney Pelvis , Magnetic Resonance Imaging , Ultrasonography , Ureteral Obstruction/diagnosis
5.
J Anim Breed Genet ; 134(2): 144-151, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27488613

ABSTRACT

The aim of this study was to evaluate the quality of the data provided from sheepdog trials in Norway, estimate heritabilities, repeatabilities and genetic correlations for the traits included in the trial and make recommendations on how sheepdog trials best can be utilized in the breeding of Border Collies in Norway. The analyses were based on test results from sheepdog trials carried out in Norway from 1993 to 2012. A total of 45 732 records from 3841 Border Collies were available, but after quality assurance only a third was left. The results demonstrated little information in the data. Heritabilities varied between 0.010 and 0.056 with standard errors ranging from 0.010 to 0.023, while repeatabilities ranged from 0.041 to 0.286. There is a need to assure the quality of data to improve the information in the test results. We recommend adding new traits based on the Herding Trait Characterization scheme evaluated in Sweden, and on traits from the predatory motor pattern, regarded as common for all dogs. These new traits may be scored across the elements that make up the current trial system, which should be kept in place to stimulate participation in the genetic evaluation scheme.


Subject(s)
Breeding , Dogs/genetics , Dogs/physiology , Animals , Dogs/classification , Female , Male , Norway , Pedigree , Predatory Behavior , Sweden
6.
Clin Exp Immunol ; 177(3): 712-9, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24773420

ABSTRACT

Sarcoidosis is a systemic, inflammatory disorder, which in a proportion of patients runs a chronic progressive course despite immunosuppressive treatment. Therapeutic granulocyte and monocyte apheresis (GMA) has been shown to be an effective treatment option for other systemic inflammatory disorders, but has not yet been investigated in sarcoidosis. The aim of this study was to evaluate the response to GMA in sarcoidosis. Seven patients with sarcoidosis refractory to standard immunosuppressive therapy received 10 GMA sessions. All patients underwent chest X-ray, spirometry, a Chronic Respiratory Disease Questionnaire (CRQ-SAS), blood tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and at 2-4 weeks and 3 months (except bronchoscopy) after the last treatment session. Bronchoalveolar lavage fluid (BALF) cell differential counts were recorded and T cells from blood and BALF were analysed for markers of activity, differentiation and T regulatory function. Compared to baseline, five of seven patients reported an improvement in dyspnoea score. In BALF there was an increase in the percentage of macrophages and a decrease in the percentage of lymphocytes and CD4(+) /FoxP3(+) T cells. Furthermore, the decrease in BALF CD4(+) /FoxP3(+) T cells correlated significantly with an improvement in dyspnoea score. In peripheral blood there was a statistically significant increase in the percentage of CD4(+) /CD27(-) T cells and a trend towards an initial increase in the percentage of CD4(+) /FoxP3(+) T cells, followed by a statistically significant decrease. The effects of GMA on regulatory T cells are consistent with those observed in other inflammatory disorders and could potentially translate into a clinical benefit.


Subject(s)
Granulocytes , Leukapheresis , Monocytes , Sarcoidosis/therapy , Adult , Bronchoalveolar Lavage Fluid/cytology , Female , Humans , Leukapheresis/methods , Leukocyte Count , Male , Middle Aged , Pilot Projects , Radiography , Sarcoidosis/diagnostic imaging , Sarcoidosis, Pulmonary/diagnostic imaging , Sarcoidosis, Pulmonary/therapy , T-Lymphocyte Subsets/metabolism , Treatment Outcome
7.
J Electromyogr Kinesiol ; 24(1): 58-64, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24182735

ABSTRACT

Neuromuscular control of the scapular muscles is important in the etiology of shoulder pain. Electromyographical (EMG) biofeedback in healthy people has been shown to support a selective activation of the lower compartment of the trapezius muscle, specifically. The aim of the present paper was to investigate whether patients with Subacromial Impingement Syndrome (SIS) were able to selectively activate the individual compartments within the trapezius muscle, with and without EMG biofeedback to the same extent as healthy controls (No-SIS). Fifteen SIS and 15 No-SIS participated in the study. Sessions with and without visual biofeedback were conducted. Surface EMG was recorded from four compartments of the trapezius muscle. Selective activation was defined as activation above 12% with other muscle parts below 1.5% or activation ratio at or above 95% of the total activation. Without biofeedback significantly fewer SIS subjects than No-SIS achieved selective activation (p=0.02-0.03). The findings of the study show that without biofeedback No-SIS had a superior scapular muscle control. However, when provided with visual EMG feedback the SIS group performed equally well as the No-SIS group. This indicated that individuals with SIS may benefit from biofeedback training to gain control of the neuromuscular function of the scapular muscle.


Subject(s)
Isometric Contraction/physiology , Shoulder Impingement Syndrome/physiopathology , Superficial Back Muscles/physiopathology , Adult , Biofeedback, Psychology , Case-Control Studies , Electromyography , Feedback, Sensory/physiology , Female , Humans , Joint Instability/physiopathology , Male , Neurofeedback , Pain Measurement , Scapula/physiopathology , Shoulder/physiopathology
8.
Equine Vet J ; 46(1): 32-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23448227

ABSTRACT

REASONS FOR PERFORMING STUDY: The pathogenesis of osteochondrosis (OC) and palmar/plantar first phalanx osteochondral fragments (POFs) is multifactorial, but specific knowledge of heritability is limited. OBJECTIVES: To improve the precision of heritability estimates and to estimate the genetic correlation between tarsocrural OC and POFs in Standardbred trotters. Further aims were to examine whether the prevalence of OC/POFs was different in the American and French lineages that have contributed to the Norwegian population, and if the prevalence was affected by heterozygosity. STUDY DESIGN: Retrospective cohort study. METHODS: Categorical data on tarsocrural OC and POFs from 2 radiographic studies performed in 1989 and 2007/2008 (n = 1217) were analysed with sire threshold models that included 230 sires. RESULTS: Heritability of OC at the distal intermediate ridge of the tibia and/or the lateral trochlear ridge of the talus was estimated at 0.29 ± 0.15. For OC at the distal intermediate ridge of the tibia only, the estimate was 0.40 ± 0.17. Heritability of POFs in all 4 limbs was estimated at 0.23 ± 0.13; for metatarsophalangeal POFs this was 0.26 ± 0.13 and for medial metatarsophalangeal POFs 0.32 ± 0.14. Estimates of genetic correlation between OC and POFs ranged from 0.68 ± 0.27 to 0.73 ± 0.28 but were not significantly different from a zero-genetic correlation. Effects of lineages or heterozygosity were not observed. CONCLUSIONS AND POTENTIAL RELEVANCE: This study confirmed a moderate to high heritability of tarsocrural OC and POF, providing further evidence of the heritable nature of these diseases. Examination of specific lesions yielded the highest heritability; therefore, breeding programmes and future genome-analysis studies should focus on predilection sites rather than the entire disease complex.


Subject(s)
Genetic Predisposition to Disease , Horse Diseases/genetics , Osteochondrosis/veterinary , Tarsus, Animal/pathology , Animals , Cohort Studies , Horses , Osteochondrosis/genetics , Osteochondrosis/pathology , Pedigree , Retrospective Studies
9.
J Comp Pathol ; 149(4): 463-74, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23746745

ABSTRACT

Sepsis is a common and often fatal complication in human patients in intensive care units. Relevant and well characterized animal models of sepsis may provide valuable information on pathophysiological mechanisms and be a mean of testing new therapeutic strategies. Large animal models of Staphylococcus aureus sepsis are rare, even though S. aureus increasingly affects human patients. Sepsis changes the haemostatic balance and leads to endothelial cell (EC) activation, coagulopathy and, in severe cases, disseminated intravascular coagulation (DIC). The aim of this study was to characterize the haemostatic and vascular alterations in a novel porcine model of severe S. aureus sepsis, investigating whether the changes fulfill the human clinical criteria for DIC. Five pigs were inoculated intravenously with S. aureus and two control animals were sham-inoculated. Blood samples were collected for thromboelastography (TEG) and assessment of plasma-based haemostatic parameters. Tissue was collected for histopathology and reverse transcriptase quantitative real-time polymerase chain reaction for measurement of mRNA encoding EC markers. All infected animals developed DIC; including procoagulant activation represented by hypercoagulable TEG profiles and prolonged clotting time. Histologically, numerous pulmonary thrombi were present in one pig. Inhibitor consumption was represented by decreasing antithrombin levels in infected pigs. Hyaline globules were found in three infected pigs, confirming fibrinolytic activation. EC activation was identified by expression of von Willebrand factor in small vessels together with elevated mRNA encoding activated EC markers. Severe haemostatic and vascular changes fulfilling the human criteria for DIC were therefore seen in all infected pigs. A tendency towards uncompensated DIC was seen in two animals.


Subject(s)
Disease Models, Animal , Disseminated Intravascular Coagulation/physiopathology , Staphylococcal Infections/physiopathology , Animals , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/pathology , Female , Humans , Real-Time Polymerase Chain Reaction , Sepsis , Staphylococcal Infections/complications , Staphylococcal Infections/pathology , Staphylococcus aureus , Swine
10.
J Anim Breed Genet ; 130(3): 170-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23679942

ABSTRACT

The aim of this study was to examine how to apply optimal contribution selection (OCS) in the Norwegian and the North-Swedish cold-blooded trotter and give practical recommendations for the future. OCS was implemented using the software Gencont with overlapping generations and selected a few, but young sires, as these turn over the generations faster and thus is less related to the mare candidates. In addition, a number of Swedish sires were selected as they were less related to the selection candidates. We concluded that implementing OCS is feasible to select sires (there is no selection on mares), and we recommend the number of available sire candidates to be continuously updated because of amongst others deaths and geldings. In addition, only considering sire candidates with phenotype above average within a year class would allow selection candidates from many year classes to be included and circumvent current limitation on number of selection candidates in Gencont (approx. 3000). The results showed that mare candidates can well be those being mated the previous year. OCS will, dynamically, recruit young stallions and manage the culling or renewal of annual breeding permits for stallions that had been previously approved. For the annual mating proportion per sire, a constraint in accordance with the maximum that a sire can mate naturally is recommended.


Subject(s)
Breeding/methods , Horses , Animals , Feasibility Studies , Inbreeding , Norway , Sexual Behavior, Animal , Software , Sweden
11.
J Intern Med ; 272(5): 465-71, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22469005

ABSTRACT

BACKGROUND: An increased percentage of CD4+ T cells is usually observed in bronchoalveolar lavage fluid (BALF) from patients with sarcoidosis. In HLA-DRB1*03-positive patients, such T cells express the T-cell receptor (TCR) AV2S3+ gene segment. It is not known whether cells found in BALF reflect those in enlarged regional lymph nodes (LNs). Therefore, the aim of this study was to compare T-cell phenotypes in BALF, blood and mediastinal LNs. METHODS: Fifteen patients underwent clinical investigation including bronchoscopy with bronchoalveolar lavage. Blood samples were drawn, and endoscopic ultrasound-guided fine-needle aspiration of enlarged mediastinal LNs was performed via the oesophagus. T cells from all three compartments were analysed by flow cytometry for markers of activity, differentiation and T regulatory function. RESULTS: The CD4/CD8 ratio was significantly higher in BALF compared with regional LNs and was also significantly higher in LNs than in blood. The CD4+ T cells were recently activated and more differentiated in BALF than in blood and LNs. There was an accumulation of T regulatory cells (FOXP3+) in LNs and a correlation between high levels of FOXP3+ cells in BALF and in LNs. In HLA-DRB1*03-positive patients, TCR AV2S3+ CD4+ T cells were predominantly localized within BALF. CONCLUSIONS: The CD4+ T-cell phenotype in BALF indicates an active ongoing specific immune response primarily localized to the alveolar space.


Subject(s)
Bronchoalveolar Lavage Fluid/immunology , CD4-Positive T-Lymphocytes/immunology , Lymph Nodes/immunology , Receptors, Antigen, T-Cell/immunology , Sarcoidosis, Pulmonary/immunology , Adult , Aged , Antigens/genetics , Antigens/immunology , Bronchoscopy/methods , Case-Control Studies , Female , Humans , Immunophenotyping , Male , Middle Aged , Receptors, Antigen, T-Cell/genetics , Sarcoidosis, Pulmonary/genetics , Statistics as Topic
12.
J Anim Breed Genet ; 129(2): 164-70, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22394238

ABSTRACT

There have been several approaches to the estimation of breeding values of performance in trotters, and the objective of this study was to validate different alternatives for genetic evaluation of racing performance in the North Swedish and Norwegian cold-blooded trotters. The current bivariate approach with the traits racing status (RACE) and earnings (EARN) was compared with a threshold-linear animal model and the univariate alternative with the performance trait only. The models were compared based on cross-validation of standardized earnings, using mean-squared errors of prediction (MSEP) and the correlation between the phenotype (Y) and the estimated breeding value (EBV). Despite possible effects of selection, a rather high estimate of heritability of EARN was found in our univariate analysis. The genetic trend estimate for EARN was clearly higher in the bivariate specification than in the univariate model, as a consequence of the considerable size of estimated heritability of RACE and its high correlation with EARN (approximately 0.8). RACE is highly influenced by ancestry rather than the on-farm performance of the horse itself. Consequently, the use of RACE in the genetic analysis may inflate the genetic trend of EARN because of a double counting of pedigree information. Although, because of the higher predictive ability of the bivariate specification, the improved ranking of animals within a year-class and the inability to discriminate between models for genetic trend, we propose to base prediction of breeding values on the current bivariate model.


Subject(s)
Horses/genetics , Physical Conditioning, Animal , Animals , Female , Linear Models , Male , Pedigree , Sports
13.
Vet Pathol ; 49(6): 950-62, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22461225

ABSTRACT

Acute respiratory distress syndrome is a common complication in severe sepsis. In pigs, the lungs play an important role in clearing systemic bacterial infections due to pulmonary intravascular macrophages found specifically in pigs. However, this increases the exposure of the porcine lungs to pathogens and potential injury. The authors propose that increasing the concentration of the inoculum without changing the bacterial dose will lead to severe sepsis with pronounced pulmonary lesions. This could potentially create a risk of cytokine spillover to the circulation, leading to an increased systemic response. Eight Danish Landrace pigs, approximately 10 weeks old, were inoculated twice with a low or once with a high concentration of Staphylococcus aureus. Three pigs were sham-inoculated. The animals were grouped based on macro- and microscopic lung lesions. The mRNA expression of local pulmonary inflammatory markers was compared to protein levels of systemic inflammatory markers. The most severe pulmonary lesions were observed in animals receiving the high S. aureus concentration, indicating that severity of lesions is dependent on inoculum concentration rather than total numbers of bacteria. Furthermore, local mRNA expression of inflammatory cytokines appeared to be dependent on the magnitude and severity of tissue destruction, including the ability to confine the lesions. Increasing mRNA levels of serum amyloid A could be a confident marker of severity of pulmonary lesions. Since no correlation was observed between local and systemic levels of inflammatory cytokines, this finding could indicate an ability of the porcine lung to compartmentalize the local inflammatory response and thus restrict systemic contribution.


Subject(s)
Cytokines/metabolism , Respiratory Distress Syndrome/veterinary , Staphylococcal Infections/veterinary , Staphylococcus aureus/physiology , Swine Diseases/pathology , Animals , Bacterial Load , Biomarkers/blood , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Female , Lung/metabolism , Lung/microbiology , Lung/pathology , Lymph Nodes/pathology , Macrophages, Alveolar/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/microbiology , Respiratory Distress Syndrome/pathology , Sepsis , Severity of Illness Index , Specific Pathogen-Free Organisms , Staphylococcal Infections/immunology , Staphylococcal Infections/microbiology , Staphylococcal Infections/pathology , Sus scrofa , Swine , Swine Diseases/immunology , Swine Diseases/microbiology
14.
Anim Genet ; 42(5): 457-65, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21906097

ABSTRACT

Mastitis is the most frequent and costly disease in dairy production and solutions leading to a reduction in the incidence of mastitis are highly demanded. Here a genome-wide association study was performed to identify polymorphisms affecting susceptibility to mastitis. Genotypes for 17 349 SNPs distributed across the 29 bovine autosomal chromosomes from a total of 2589 sires with 1 389 776 daughters with records on clinical mastitis were included in the analysis. Records of occurrence of clinical mastitis were divided into seven time periods in the first three lactations in order to identify quantitative trait loci affecting mastitis susceptibility in particular phases of lactation. The most convincing results from the association mapping were followed up and validated by a combined linkage disequilibrium and linkage analysis. The study revealed quantitative trait loci affecting occurrence of clinical mastitis in the periparturient period on chromosomes 2, 6 and 20 and a quantitative trait locus affecting occurrence of clinical mastitis in late lactation on chromosome 14. None of the quantitative trait loci for clinical mastitis detected in the study seemed to affect lactation average of somatic cell score. The SNPs highly associated with clinical mastitis lie near both the gene encoding interleukin 8 on chromosome 6 and the genes encoding the two interleukin 8 receptors on chromosome 2.


Subject(s)
Genome-Wide Association Study , Mastitis, Bovine/genetics , Quantitative Trait Loci , Animals , Cattle , Chromosomes, Mammalian , Female , Genetic Predisposition to Disease , Linkage Disequilibrium , Male , Polymorphism, Single Nucleotide
15.
Anim Genet ; 42(5): 466-74, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21906098

ABSTRACT

Reproductive performance is a critical trait in dairy cattle. Poor reproductive performance leads to prolonged calving intervals, higher culling rates and extra expenses related to multiple inseminations, veterinary treatments and replacements. Genetic gain for improved reproduction through traditional selection is often slow because of low heritability and negative correlations with production traits. Detection of DNA markers associated with improved reproductive performance through genome-wide association studies could lead to genetic gain that is more balanced between fertility and production. Norwegian Red cattle are well suited for such studies, as very large numbers of detailed reproduction records are available. We conducted a genome-wide association study for non-return rate, fertility treatments and retained placenta using almost 1 million records on these traits and 17 343 genome-wide single-nucleotide polymorphisms. Genotyping costs were minimized by genotyping the sires of the cows recorded and by using daughter averages as phenotypes. The genotyped sires were assigned to either a discovery or a validation population. Associations were only considered to be validated if they were significant in both groups. Strong associations were found and validated on chromosomes 1, 5, 8, 9, 11 and 12. Several of these were highly supported by findings in other studies. The most important result was an association for non-return rate in heifers in a region of BTA12 where several associations for milk production traits have previously been found. Subsequent fine-mapping verified the presence of a quantitative trait loci (QTL) having opposing effects on non-return rate and milk production at 18 Mb. The other reproduction QTL did not have pleiotropic effects on milk production, and these are therefore of considerable interest for use in marker-assisted selection.


Subject(s)
Cattle/genetics , Genome-Wide Association Study , Lactation , Quantitative Trait Loci , Reproduction , Animals , Cattle/physiology , Female , Male , Milk , Pregnancy
16.
Pharmacogenomics J ; 10(6): 513-23, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20157331

ABSTRACT

The dose of docetaxel is currently calculated based on body surface area and does not reflect the pharmacokinetic, metabolic potential or genetic background of the patients. The influence of genetic variation on the clearance of docetaxel was analysed in a two-stage analysis. In step one, 583 single-nucleotide polymorphisms (SNPs) in 203 genes were genotyped on samples from 24 patients with locally advanced non-small cell lung cancer. We found that many of the genes harbour several SNPs associated with clearance of docetaxel. Most notably these were four SNPs in EGF, three SNPs in PRDX4 and XPC, and two SNPs in GSTA4, TGFBR2, TNFAIP2, BCL2, DPYD and EGFR. The multiple SNPs per gene suggested the existence of common haplotypes associated with clearance. These were confirmed with detailed haplotype analysis. On the basis of analysis of variance (ANOVA), quantitative mutual information score (QMIS) and Kruskal-Wallis (KW) analysis SNPs significantly associated with clearance of docetaxel were confirmed for GSTA4, PRDX4, TGFBR2 and XPC and additional putative markers were found in CYP2C8, EPHX1, IGF2, IL1R2, MAPK7, NDUFB4, TGFBR3, TPMT (2 SNPs), (P<0.05 or borderline significant for all three methods, 14 SNPs in total). In step two, these 14 SNPs were genotyped in additional 9 samples and the results combined with the genotyping results from the first step. For 7 of the 14 SNPs, the results are still significant/borderline significant by all three methods: ANOVA, QMIS and KW analysis strengthening our hypothesis that they are associated with the clearance of docetaxel.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Reactive Oxygen Species/metabolism , Taxoids/pharmacokinetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Docetaxel , Haplotypes , Humans , Linkage Disequilibrium , Polymorphism, Single Nucleotide , Taxoids/metabolism
17.
Anim Genet ; 41(3): 273-80, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19968646

ABSTRACT

Dystocia and stillbirth are significant causes of female and neonatal death in many species and there is evidence for a genetic component to both traits. Identifying causal mutations affecting these traits through genome wide association studies could reveal the genetic pathways involved and will be a step towards targeted interventions. Norwegian Red cattle are an ideal model breed for such studies as very large numbers of records are available. We conducted a genome wide association study for direct and maternal effects of dystocia and stillbirth using almost 1 million records of these traits. Genotyping costs were minimized by genotyping the sires of the recorded cows, and using daughter averages as phenotypes. A dense marker map containing 17,343 single nucleotide polymorphisms covering all autosomal chromosomes was utilized. The genotyped sires were assigned to one of two groups in an attempt to ensure independence between the groups. Associations were only considered validated if they occurred in both groups. Strong associations were found and validated on chromosomes 4, 5, 6, 9, 12, 20, 22 and 28. The QTL region on chromosome 6 was refined using LDLA analysis. The results showed that this chromosome most probably contains two QTL for direct effect on dystocia and one for direct effect on stillbirth. Several candidate genes may be identified close to these QTL. Of these, a cluster of genes expected to affect bone and cartilage formation (i.e. SPP1, IBSP and MEPE) are of particular interest and we suggest that these genes are screened in candidate gene studies for dystocia and stillbirth in cattle as well as other species.


Subject(s)
Cattle Diseases/genetics , Dystocia/veterinary , Genome-Wide Association Study , Quantitative Trait Loci , Stillbirth/veterinary , Animals , Cattle , Dystocia/genetics , Female , Polymorphism, Single Nucleotide , Pregnancy
18.
Acta Anaesthesiol Scand ; 54(4): 430-4, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19878101

ABSTRACT

BACKGROUND: In vitro and in vivo studies have indicated that stabilizers present in pharmaceutical-grade albumin influence the albumin-binding capacity for highly protein-bound drugs. However, the half-life of the stabilizers and the quantitative effect have been difficult to determine. METHOD: A randomized crossover study including six healthy volunteers was performed. The study subjects received 750 mg of oral naproxen 2 h before the study. They were randomized to receive either 100 ml of 20% albumin or 100 ml of Ringer's acetate solution intravenously. Frequent blood samples were obtained. The experiment was repeated 4 weeks later with the alternate solution. The serum samples were analysed to determine the concentrations of albumin, N-acetyl-DL-tryptophan, caprylate, and naproxen. RESULTS: The free fraction of naproxen increased significantly after the infusion of albumin (P<0.05). The increase was concurrent with the appearance of N-acetyl-DL-tryptophan and caprylate in serum. The free fraction of naproxen declined rapidly after the albumin infusion was completed. N-acetyl-DL-tryptophan had a half-life of approximately 30 min. The half-life of caprylate was <15 min. CONCLUSION: A transfusion of albumin results in an increase in the free fraction of naproxen. The transient increase in free-fraction naproxen decreased together with the detectable levels of the stabilizers N-acetyl-DL-tryptophan and caprylate. N-acetyl-DL-tryptophan and caprylate have a short half-life in serum.


Subject(s)
Albumins/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Naproxen/pharmacokinetics , Adult , Albumins/administration & dosage , Caprylates/pharmacokinetics , Cross-Over Studies , Female , Half-Life , Humans , Immunohistochemistry , Indicators and Reagents , Infusions, Intravenous , Male , Middle Aged , Pharmaceutic Aids , Treatment Outcome , Tryptophan/analogs & derivatives , Tryptophan/pharmacokinetics , Young Adult
19.
J Electromyogr Kinesiol ; 20(2): 359-65, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19342256

ABSTRACT

Motor control and learning possibilities of scapular muscles are of clinical interest for restoring scapular muscle balance in patients with neck and shoulder disorders. The aim of the study was to investigate whether selective voluntary activation of intra-muscular parts within the serratus anterior can be learned with electromyographical (EMG) biofeedback, and whether the lower serratus anterior and the lower trapezius muscle comprise the lower scapula rotation force couple by synergistic activation. Nine healthy males practiced selective activation of intra-muscular parts within the serratus anterior with visual EMG biofeedback, while the activity of four parts of the serratus anterior and four parts of the trapezius muscle was recorded. One subject was able to selectively activate both the upper and the lower serratus anterior respectively. Moreover, three subjects managed to selectively activate the lower serratus anterior, and two subjects learned to selectively activate the upper serratus anterior. During selective activation of the lower serratus anterior, the activity of this muscle part was 14.4+/-10.3 times higher than the upper serratus anterior activity (P<0.05). The corresponding ratio for selective upper serratus vs. lower serratus anterior activity was 6.4+/-1.7 (P<0.05). Moreover, selective activation of the lower parts of the serratus anterior evoked 7.7+/-8.5 times higher synergistic activity of the lower trapezius compared with the upper trapezius (P<0.05). The learning of complete selective activation of both the lower and the upper serratus anterior of one subject, and selective activation of either the upper or lower serratus anterior by five subjects designates the promising clinical application of EMG biofeedback for restoring scapular muscle balance. The synergistic activation between the lower serratus anterior and the lower trapezius muscle was observed in only a few subjects, and future studies including more subjects are required before conclusions of a lower scapula rotation couple can be drawn.


Subject(s)
Biofeedback, Psychology/methods , Biofeedback, Psychology/physiology , Electromyography/methods , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Postural Balance/physiology , Scapula/physiology , Adult , Humans , Male , Muscular Diseases/physiopathology , Muscular Diseases/rehabilitation
20.
Anim Genet ; 40(5): 701-12, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19466933

ABSTRACT

Quantitative trait loci affecting clinical mastitis were detected and fine mapped to a narrow region on bovine chromosome 6 in the Norwegian Red cattle population. The region includes the casein gene cluster and several candidate genes thought to influence clinical mastitis. The most significant results were found for SNPs within the Mucin 7 gene. This gene encodes an antimicrobial peptide and constitutes part of the first line of defence for the mucosal immune system. Detection of long haplotypes extending several Mb may indicate that artificial selection has influenced the haplotype structures in the region. A search for selection sweeps supports this observation and coincides with association results found both by single SNP and haplotype analyses. Our analyses identified haplotypes carrying quantitative trait loci alleles associated with high protein yield and simultaneously fewer incidences of clinical mastitis. The fact that such haplotypes are found in relative high frequencies in Norwegian Red may reflect the combined breeding goal that is characterized by selection for both milk production and disease resistance. The identification of these haplotypes raises the possibility of overcoming the unfavourable genetic correlation between these traits through haplotype-assisted selection.


Subject(s)
Chromosome Mapping/veterinary , Mastitis, Bovine/genetics , Quantitative Trait Loci/genetics , Animals , Cattle , Female , Genetic Markers/genetics , Haplotypes/genetics , Linkage Disequilibrium/genetics , Mastitis, Bovine/pathology , Polymorphism, Single Nucleotide , Selection, Genetic
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