Genomic Analysis of Inbreeding and Coancestry in Nordic Jersey and Holstein Dairy Cattle Populations.

In recent years, Genomic Selection (GS) has accelerated genetic gain in dairy cattle breeds worldwide. Despite the evident genetic progress, several dairy populations have also encountered challenges such as heightened inbreeding rates and reduced effective population sizes. The challenge has been to find a balance between achieving substantial genetic gain while managing genetic diversity within the population, thereby mitigating the negative effects of inbreeding depression. This study aims to elucidate the impact of GS on pedigree and genomic rates of inbreeding (ΔF) and coancestry (ΔC) in Nordic Jersey (NJ) and Holstein (NH) cattle populations. Furthermore, key genetic metrics including the generation interval (L), effective population size (Ne), and future effective population size (FNe) were assessed between 2 time periods, before and after GS, and across distinct animal cohorts in both breeds: females, bulls, and approved semen-producing bulls (AI-sires). Analysis of ΔF and ΔC revealed distinct trends across the studied periods and animal groups. Notably, there was a consistent increase in yearly ΔF for most animal groups in both breeds. An exception was observed in NH AI-sires, which demonstrated a slight decrease in yearly ΔF. Moreover, NJ displayed minimal changes in yearly ΔC between the periods, whereas NH exhibited elevated ΔC values across all animal groups. Particularly striking was the substantial increase in yearly ΔC within the NH female population, surging from 0.02% to 0.39% between the periods. Implementation of GS resulted in a reduction of the generation interval across all animal cohorts in both NJ and NH breeds. However, the extent of reduction was more pronounced in males compared with females. This reduction in generation interval influenced generational changes in ΔF and ΔC. Bulls and AI-sires of both breeds exhibited reduced generational ΔF between periods, in contrast to females that demonstrated an opposing pattern. Between the periods, NJ maintained a relatively stable Ne, 29.4 before and 30.3 after GS, while NH experienced a notable decline from 54.3 to 42.8. Female groups in both breeds displayed a negative Ne trend, while males demonstrated either neutral or positive Ne developments. Regarding FNe, NJ exhibited positive FNe development with an increase from 40.7 to 57.2. The opposite was observed in NH, where FNe decreased from 198.8 to 42.7. In summary, it was evident that the genomic methods could detect differences between the populations and changes in ΔF and ΔC more efficiently than pedigree methods. GS implementation yielded positive outcomes within the NJ population regarding the rate of coancestry but the opposite was observed with NH. Moreover, analysis of ΔC data hints at the potential to decrease future ΔF through informed mating strategies. Conversely, NH faces more pressing concerns, even though ΔF remains comparatively modest in contrast to what has been observed in other Holstein populations. These findings underscore the necessity of genomic control of inbreeding and coancestry with strategic changes in the Nordic breeding schemes for dairy to ensure long-term sustainability in the forthcoming years.

Correlation between breeding values for milk fatty acids and Nordic Total Merit index traits for Danish Holstein and Danish Jersey.

Milk fatty acid composition is gaining interest in the Danish dairy industry both to develop new dairy products and as a management tool. To be able to implement milk fatty acid (FA) composition in the breeding program, it is important to know the correlations with the traits in the breeding goal. To estimate these correlations, we measured milk fat composition in Danish Holstein (DH) and Danish Jersey (DJ) cattle breeds using mid-infrared spectroscopy. Breeding values were estimated for specific FA and for groups of FA. Correlations with the estimated breeding values (EBV) underlying the Nordic Total Merit index (NTM) were calculated within breed. For both DH and DJ, we showed that FA EBV had moderate correlations with the NTM and production traits. For both DH and DJ, the correlation of FA EBV and NTM were in the same direction, except for C16:0 (0 in DH, 0.23 in DJ). A few correlations differed between DH and DJ. The correlation between claw health index and C18:0 was negative in DH (-0.09) but positive in DJ (0.12). In addition, some correlations were not significant in DH but were significant in DJ. The correlations between udder health index and long-chain FA, trans FA, C16:0, and C18:0 were not significant in DH (-0.05 to 0.02), but were significant in DJ (-0.17, -0.15, 0.14, and -0.16, respectively). For both DH and DJ, the correlations between FA EBV and nonproduction traits were low. This implies that it is possible to breed for a different fat composition in the milk without affecting the nonproduction traits in the breeding goal.

Genetic analysis of predicted fatty acid profiles of milk from Danish Holstein and Danish Jersey cattle populations.

The objective of this study was to assess the genetic variability of the detailed fatty acid (FA) profiles of Danish Holstein (DH) and Danish Jersey (DJ) cattle populations. We estimated genetic parameters for 11 FA or groups of FA in milk samples from the Danish milk control system between May 2015 and October 2016. Concentrations of different FA and FA groups in milk samples were measured by mid-infrared spectroscopy. Data used for parameter estimation were from 132,732 first-parity DH cows and 21,966 first-parity DJ cows. We found the highest heritabilities for test day measurements in both populations for short-chain FA (DH = 0.16; DJ = 0.16) and C16:0 (DH = 0.14; DJ = 0.16). In DH, the highest heritabilities were also found for saturated FA and monounsaturated FA (both populations: 0.15). Genetic correlations between the fatty acid traits showed large differences between DH and DJ for especially short-chain FA with the other FA traits measured. Furthermore, genetic correlations of total fat with monounsaturated FA, polyunsaturated FA, short-chain FA, and C16:0 differed markedly between DH and DJ populations. In conclusion, we found genetic variation in the mid-infrared spectroscopy-predicted FA and FA groups of the DH and DJ cattle populations. This finding opens the possibility of using genetic selection to change the FA profiles of dairy cattle.

Bivariate threshold models for genetic evaluation of susceptibility to and ability to recover from mastitis in Danish Holstein cows.

Mastitis in dairy cows is an unavoidable problem and genetic variation in recovery from mastitis, in addition to susceptibility, is therefore of interest. Genetic parameters for susceptibility to and recovery from mastitis were estimated for Danish Holstein-Friesian cows using data from automatic milking systems equipped with online somatic cell count measuring units. The somatic cell count measurements were converted to elevated mastitis risk, a continuous variable [on a (0-1) scale] indicating the risk of mastitis. Risk values >0.6 were assumed to indicate that a cow had mastitis. For each cow and lactation, the sequence of health states (mastitic or healthy) was converted to a weekly transition: 0 if the cow stayed within the same state and 1 if the cow changed state. The result was 2 series of transitions: one for healthy to diseased (HD, to model mastitis susceptibility) and the other for diseased to healthy (DH, to model recovery ability). The 2 series of transitions were analyzed with bivariate threshold models, including several systematic effects and a function of time. The model included effects of herd, parity, herd-test-week, permanent environment (to account for the repetitive nature of transition records from a cow) plus two time-varying effects (lactation stage and time within episode). In early lactation, there was an increased risk of getting mastitis but the risk remained stable afterwards. Mean recovery rate was 45% per lactation. Heritabilities were 0.07 [posterior mean of standard deviations (PSD) = 0.03] for HD and 0.08 (PSD = 0.03) for DH. The genetic correlation between HD and DH has a posterior mean of -0.83 (PSD = 0.13). Although susceptibility and recovery from mastitis are strongly negatively correlated, recovery can be considered as a new trait for selection.

Lipoprotein lipase activity does not predict very low-density lipoprotein-triglyceride fatty acid oxidation during exercise.

Exercise lowers plasma triglyceride levels, but the physiological mechanisms remain not fully elucidated. Lipoprotein lipase (LPL) is a key enzyme in facilitating fatty acid uptake from lipoproteins. As exercise increases the efficiency of very low-density lipoprotein-triglyceride (VLDL-TG) oxidation, we hypothesized that muscle LPL activity would be a rate-limiting step and predict VLDL-TG Fatty acids oxidation during exercise. Sixteen healthy, lean subjects (eight men and eight women) were examined before and during an acute exercise bout (90 minutes at 50% of VO2-max). Heparin-releasable LPL activity was measured in muscle and adipose tissue biopsies. Breath 14 CO2 was measured after a primed-constant infusion of ex vivo labeled [14 C]-triolein VLDL-TG. Fractional VLDL-TG storage was measured in adipose tissue biopsies. Exercise did not affect muscle LPL activity (P=.30). No association was observed between muscle LPL activity and VLDL-TG oxidation, neither in the basal state (P=.17) nor during exercise (P=.83). Exercise did not affect upper body or lower body adipose tissue LPL activity (both P=.92). The basal adipose tissue fractional VLDL-TG storage (abdominal.13%±9%; femoral 17%±10% (P=.18)) was not associated with upper body (P=.56) or lower body (P=.44) subcutaneous adipose tissue LPL activity. Muscle LPL activity does not predict VLDL-TG oxidation during rest or exercise. In addition, adipose tissue LPL activity was not associated with VLDL-TG storage during rest. This suggests that LPL activity is present in excess of what is required to facilitate lipid uptake for oxidation during both rest and exercise.

Monitoring individual cow udder health in automated milking systems using online somatic cell counts.

This study presents and validates a detection and monitoring model for mastitis based on automated frequent sampling of online cell count (OCC). Initially, data were filtered and adjusted for sensor drift and skewed distribution using ln-transformation. Acceptable data were passed on to a time-series model using double exponential smoothing to estimate level and trends at cow level. The OCC levels and trends were converted to a continuous (0-1) scale, termed elevated mastitis risk (EMR), where values close to zero indicate healthy cow status and values close to 1 indicate high risk of mastitis. Finally, a feedback loop was included to dynamically request a time to next sample, based on latest EMR values or errors in the raw data stream. The estimated EMR values were used to issue 2 types of alerts, new and (on-going) intramammary infection (IMI) alerts. The new alerts were issued when the EMR values exceeded a threshold, and the IMI alerts were issued for subsequent alerts. New alerts were only issued after the EMR had been below the threshold for at least 8d. The detection model was evaluated using time-window analysis and commercial herd data (6 herds, 595,927 milkings) at different sampling intensities. Recorded treatments of mastitis were used as gold standard. Significantly higher EMR values were detected in treated than in contemporary untreated cows. The proportion of detected mastitis cases using new alerts was between 28.0 and 43.1% and highest for a fixed sampling scheme aiming at 24h between measurements. This was higher for IMI alerts, between 54.6 and 89.0%, and highest when all available measurements were used. The lowest false alert rate of 6.5 per 1,000 milkings was observed when all measurements were used. The results showed that a dynamic sampling scheme with a default value of 24h between measurements gave only a small reduction in proportion of detected mastitis treatments and remained at 88.5%. It was concluded that filtering of raw data combined with a time-series model was effective in detecting and monitoring mastitis status in dairy cows when based on IMI alerts, and by using a dynamically adjusting sampling scheme almost full performance was still obtainable. However, results were less desirable when based on new alerts most likely because of the used gold standard for mastitis, which may not necessarily reflect the onset of and IMI case in contrast to a new alert.

Short communication: Effects of Bos taurus autosome 9-located quantitative trait loci haplotypes on enzymatic mastitis indicators of milk from dairy cows experimentally inoculated with Escherichia coli.

The aim of this study was to investigate the effect of a quantitative trait locus associated with mastitis caused by Escherichia coli, with one haplotype being more susceptible (HH) and another being more resistant (HL) to E. coli mastitis, on the activity of 4 inflammatory related milk enzymes. In particular, we investigated the suitability of ß-glucuronidase (GLU) as an early indicator of E. coli mastitis. Besides GLU, the enzymes l-lactate dehydrogenase (LDH), N-acetyl-ß-d-glucosaminidase (NAGase), and alkaline phosphatase were included. The study was conducted in an experimental setup with 31 Holstein cows divided into 4 groups representing repeated experiments and, within group, divided according to quantitative trait locus haplotype. All cows were inoculated with viable E. coli, and milk samples were collected 27 times from -6 to 396 h post-E. coli inoculation (PI). Activity of the 4 enzymes in milk, somatic cell count (SCC), daily milk yield, viable E. coli counts, and results of a semiquantitative polymerase chain reaction for pathogen detection, were all analyzed with a repeatability model. The response variables all expressed a strong reaction to the E. coli infection. Daily milk yield decreased significantly at 12 h PI and bacteria counts increased 100-fold and peaked at 18 h PI, which was validated by PCR. Also, SCC started to increase at 12 h PI and increased on average 70 times; however, no significant differences in SCC level were detected between HH and HL cows at any sampling point. The enzymes LDH, NAGase, and alkaline phosphatase showed similar responses, with a significantly increased activity and higher peak values for the HH than the HL cows. Significant differences between HH and HL cows were detected at different time points for these 3 enzymes, but not after adjusting P-values for multiple testing. A different pattern was also observed for GLU, where HL cows expressed the highest peak activity. Indication of differences in GLU activity between the 2 haplotype groups was only seen at 60 h PI. It was concluded that HL and HH cows expressed similar response patterns after E. coli infection but with differences in the size and profile of the activity of the 4 enzymes. The enzyme GLU was an equally good indicator of E. coli mastitis compared with the other studied enzymes, although it showed a slower response compared with LDH and NAGase.

Emergency patients receiving anaesthesiologist-based pre-hospital treatment and subsequently released at the scene.

BACKGROUND: The Mobile Emergency Care Unit in Odense, Denmark consists of a rapid response car, manned with an anaesthesiologist and an emergency medical technician. Eleven per cent of the patients are released at the scene following treatment. The aim of the study was to investigate which diagnoses were assigned to patients released at the scene following treatment, to investigate the need for secondary contact with the hospital and to assess mortality in patients released at the scene. METHODS: All records regarding patients released at the scene from 1 January 2008 to 31 December 2010 were investigated. In each patient, diagnosis as well as any renewed contact with the Mobile Emergency Care Unit or the hospital within 24 h was registered. RESULTS: One thousand six hundred nine: patients were released at the scene. Diagnoses within the category 'examination and investigation' [International Classification of Diseases 10th revision (ICD-10) chapter XXI] represented the largest group of patients (28%). Diseases not elsewhere classified (ICD-10 chapter XVIII) including 'syncope and collapse' represented the second largest group of patients (24%). One hundred thirteen (7%) had a renewed contact with the Mobile Emergency Care Unit within 24 h. Of the 143 victims of traffic accidents, 19 (13%) required renewed contact with the emergency department and one required admission to hospital (0.7%). Of all 1609 patients, four died within 24 h of contact (0.2%). CONCLUSION: Patients treated and released at the scene presented poorly defined conditions. Ninety-three per cent of all cases required no secondary contacts with the health care system. However, caution should be exercised when releasing patients at the scene following traffic accidents.

Effects of Bos taurus autosome 9-located quantitative trait loci haplotypes on the disease phenotypes of dairy cows with experimentally induced Escherichia coli mastitis.

Several quantitative trait loci (QTL) affecting mastitis incidence and mastitis-related traits such as somatic cell score exist in dairy cows. Previously, QTL haplotypes associated with susceptibility to Escherichia coli mastitis in Nordic Holstein-Friesian (HF) cows were identified on Bos taurus autosome 9. In the present study, we induced experimental E. coli mastitis in Danish HF cows to investigate the effect of 2 E. coli mastitis-associated QTL haplotypes on the cows' disease phenotypes and recovery in early lactation. Thirty-two cows were divided in 2 groups bearing haplotypes with either low (HL) or high (HH) susceptibility to E. coli. In addition, biopsies (liver and udder) were collected from half of the cows (n=16), resulting in a 2 × 2 factorial design, with haplotype being one factor (HL vs. HH) and biopsy being the other factor (biopsies vs. no biopsies). Each cow was inoculated with a low E. coli dose (20 to 40 cfu) in one front quarter at time 0 h. Liver biopsies were collected at -144, 12, 24, and 192 h; udder biopsies were collected at 24h and 192 h post-E. coli inoculation. The clinical parameters: feed intake, milk yield, body temperature, heart rate, respiration rate, rumen motility; and the paraclinical parameters: bacterial counts, somatic cell count (SCC), and milk amyloid A levels in milk; and white blood cell count, polymorphonuclear neutrophilic leukocyte (PMNL) count, and serum amyloid A levels in blood were recorded at different time points post-E. coli inoculation. Escherichia coli inoculation changed the clinical and paraclinical parameters in all cows except one that was not infected. Clinically, the HH group tended to have higher body temperature and heart rate than the HL group did. Paraclinically, the HL group had faster PMNL recruitment and SCC recovery than the HH group did. However, we also found interactions between the effects of haplotype and biopsy for body temperature, heart rate, and PMNL. In conclusion, when challenged with E. coli mastitis, HF cows with the specific Bos taurus autosome 9-located QTL haplotypes were associated with differences in leukocyte kinetics, with low-susceptibility cows having faster blood PMNL recruitment and SCC recovery and a tendency for a milder clinical response than the high-susceptibility cows did.

Postprandial VLDL-triacylglycerol secretion is not suppressed in obese type 2 diabetic men.

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by insulin resistance and increased post-absorptive secretion of VLDL-triacylglycerol (VLDL-TAG). Whether postprandial suppression of endogenous VLDL-TAG secretion is abnormal--a finding that would link hyperlipidaemia and type 2 diabetes--remains unclear. METHODS: Eight type 2 diabetic men and eight healthy men were studied before and after a fat-free test meal (40% of resting energy expenditure). VLDL-TAG kinetics were assessed using a primed-constant infusion of ex vivo labelled [1-(14)C]triolein VLDL-TAG using non-steady-state calculations. RESULTS: Type 2 diabetic men had a higher basal VLDL-TAG secretion rate and concentration than healthy men (mean ± SD secretion rate 137 ± 61 vs 78 ± 30 µmol/min, respectively [p = 0.03]; median concentration 1.03 [range 0.58-1.75] vs 0.33 [0.13-1.14] mmol/l, respectively [p < 0.01]). Postprandially, the VLDL-TAG secretion rate decreased in healthy men (p < 0.01), but remained unchanged in diabetic men (p = 0.47). The VLDL-TAG concentration increased in diabetic men and decreased in healthy men postprandially (p < 0.05). The difference in VLDL-TAG secretion rate between the two groups approached significance (p = 0.06) and the relative change in VLDL-TAG secretion rate was significantly different (p = 0.01) between the two groups. Basal VLDL-TAG clearance was significantly lower in diabetic men (diabetic men 133 [49-390] ml/min; healthy controls 215 [137-933] ml/min [p < 0.05]). After meal ingestion, clearance decreased in healthy men (p = 0.03), but was unchanged in diabetic men (p = 0.58). CONCLUSIONS/INTERPRETATION: Obese type 2 diabetic men have impaired postprandial suppression of VLDL-TAG secretion compared with lean healthy men, contributing to their postprandial lipaemia and hypertriacylglycerolaemia.

Soluble CD163: a biomarker linking macrophages and insulin resistance.

AIMS/HYPOTHESIS: Soluble CD163 (sCD163) was recently identified as a strong risk marker for developing type 2 diabetes. We hypothesised that sCD163 independently associates with insulin resistance. METHODS: This cross-sectional study includes 234 participants: 96 with type 2 diabetes, 34 with impaired glucose tolerance (IGT) and 104 with normal glucose tolerance (NGT), matched for sex and BMI. Glucose-lowering medication was paused for 1 week before plasma samples were obtained for determination of sCD163 and other inflammatory and metabolic variables. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Concentrations of sCD163 were 1.95 mg/l (0.63-6.97) in individuals with type 2 diabetes, 1.64 mg/l (0.58-4.19) in those with IGT, and 1.48 mg/l (0.48-4.11) (median [range]) in those with NGT (p < 0.0001). In univariate analyses, sCD163 correlated significantly with HOMA-IR (R = 0.44), insulin (R = 0.41), glucose (R = 0.30), triacylglycerol (R = 0.29) and HDL-cholesterol (R = -0.34) (all p < 0.0001). All but glucose remained significant when adjusting for age, sex, BMI and glycaemic group. In univariate regression analyses, HOMA-IR was associated with sCD163, C-reactive protein (CRP), TNF-α and IL-6 (all p ≤ 0.0001). An increase of 50% in sCD163 resulted in an estimated increase in HOMA-IR of 36% (95% CI 26, 48; p < 0.0001). In multiple linear regression analyses, sCD163 (p = 0.001) and CRP (p = 0.01) remained independent predictors of HOMA-IR, whereas TNF-α and IL-6 did not. CONCLUSIONS/INTERPRETATION: Macrophage-specific sCD163 was strongly associated with insulin resistance independently of TNF-α and other predictors. Moreover, sCD163 was associated with well-known variables of the metabolic syndrome.

Similarity of pharmacodynamic effects of a single injection of insulin glargine, insulin detemir and NPH insulin on glucose metabolism assessed by 24-h euglycaemic clamp studies in healthy humans.

AIMS: Two long-acting insulin analogues, insulin glargine and insulin detemir, have been developed as alternatives to neutral protamine Hagedorn (NPH) insulin, which has been the preferred basal insulin preparation for decades. The aim was to directly compare the pharmacodynamic properties of the long-acting insulin analogues and NPH insulin after a single subcutaneous injection. METHODS: The study was conducted as a double-blind, controlled, three-arm, crossover study including 10 healthy lean male volunteers. On three different occasions, each subject was challenged with 0.4 U kg(-1) of either insulin glargine, insulin detemir or NPH insulin. Plasma glucose was maintained at 0.3 mmol l(-1) below fasting level by glucose clamping for 24 h. C-peptide, insulin, free fatty acids (FFAs) and counter regulatory hormones were measured throughout the clamp period, whereas endogenous glucose release (EGR) was assessed by isotope dilution technique (3-(3)H-glucose). RESULTS: The mean glucose infusion rate (GIR)-time profiles revealed no significant differences between the three preparations in the primary endpoints: Maximal GIR of approximately 3.4 mg kg(-1) min(-1) (P = 0.68), time to maximal GIR of approximately 10 h (TR(max)) (P = 0.35) and area under the GIR curve (GIR(AUC)) (P = 0.81). Compared with the other insulin preparations, EGR (see above)was lower for insulin detemir at the beginning of the clamp period (330-360 min) (P = 0.007) while GIR was lower (P = 0.005) and FFA concentrations were higher (P = 0.005) during the last 4 h of the clamp. CONCLUSIONS: In this experimental design, only minor pharmacodynamic differences were demonstrated between insulin detemir, insulin glargine and NPH insulin.

Economic values and expected effect of selection index for pathogen-specific mastitis under Danish conditions.

The objectives of this study were 1) to estimate costs related to 5 different pathogen-specific mastitis traits (susceptibility to different pathogens causing mastitis in dairy cattle) and unspecific mastitis, and 2) to compare selection differentials for an udder health index consisting of 5 different pathogen-specific mastitis traits and lactation average somatic cell count from 5 to 170 d after first calving (LASCC170) with another index consisting of 1 unspecific mastitis trait and LASCC170. Economic values were estimated for mastitis caused by Staphylococcus aureus, Streptococcus dysgalactiae, Escherichia coli, coagulase-negative staphylococci, and Streptococcus uberis using a stochastic simulation model (SimHerd IV). Mastitis incidences for SimHerd IV were from incidences of mastitis treatments in primiparous Danish Holstein cows calving in 2007. Estimated costs ranged from 149 euro to 570 euro per mastitis case and were highest for contagious pathogens such as Staph. aureus and coagulase-negative staphylococci and lowest for Strep. dysgalactiae and Strep. uberis. The value for unspecific mastitis was 231 euro per case. Selection differentials (in euro) were estimated for 4 different selection indices, including 1) unspecific mastitis, 2) unspecific mastitis and LASCC170, 3) 5 pathogen-specific mastitis traits and unspecific residual mastitis (unspecific mastitis treatments minus mastitis treatments caused by the 5 pathogens), and 4) as index 3 including LASCC170. The breeding goal was identical to selection index 3. Mastitis data from primiparous cows calving from 1998 to 2008 were used to estimate genetic parameters of the mastitis traits using linear models and AI-REML algorithm. These parameters were used for construction of the selection index equations. For the selection indices, information sources were measurements of mastitis treatments and LASCC170 from 50, 80, or 130 daughters of a bull as well as measurements of mastitis treatments from 1,000 progeny of the bull's sire and 1,000 daughters of his maternal grandsire. Differences in selection differentials were marginal among the 4 indices. Without considering LASCC170, the selection differential of an unspecific mastitis index was 0.4 euro (<1%) better than that of a pathogen-specific index. On the other hand, the selection differential of the pathogen-specific index was 0.3 euro (<1%) better than that of an unspecific index when LASCC170 was included in the indices. Reliabilities of the selection indices were 0.62 to 0.67 (80 daughters) and were proportional to the selection differential. Changing the number of daughters to 50 or 130 did not change ranking of the indices. Heritabilities of the pathogen-specific traits were very low (h(2)=0.005-0.021) compared with unspecific mastitis (h(2)=0.062), which may limit the selection differential of the pathogen-specific index.

Genetic correlations between pathogen-specific mastitis and somatic cell count in Danish Holsteins.

The aim of this study was to estimate genetic correlations (r(a)) between 2 lactation average somatic cell count (LASCC) traits and 6 different mastitis traits in 226,482 first-parity Danish Holstein cows that calved between 1998 and 2008. The LASCC traits were defined from 5 to either 170 d (LASCC_170) or 300 d (LASCC_300) after calving, and the mastitis traits were unspecific mastitis (all mastitis treatments, both clinical and subclinical, regardless of the causative pathogen) and mastitis caused by either Streptococcus dysgalactiae, Escherichia coli, coagulase-negative staphylococci (CNS), Staphylococcus aureus, or Streptococcus uberis. Variance components were estimated using bivariate threshold-Gaussian models via Gibbs sampling. The posterior means of r(a) between LASCC_170 and the mastitis traits were greatest for unspecific mastitis (r(a) = 0.71), followed by CNS, Strep. dysgalactiae, Strep. uberis, and E. coli (r(a) = 0.54 to 0.69) and were lowest for Staph. aureus mastitis (r(a) = 0.44). The genetic correlation between LASCC_300 and the mastitis traits were generally smaller (r(a) = 0.47 to 0.69). Caution should be taken when interpreting the results, however, because some posterior density intervals for r(a) were large (between 0.14 and 0.47 units). Phenotypically, Staph. aureus is known to be associated with high SCC and especially with subclinical mastitis through chronic infections, so the low r(a) between Staph. aureus mastitis and LASCC, compared with r(a) for the other pathogens, was not expected. Subclinical cases are usually submitted to dry cow therapy (not included in the present study), not treated at all, or wrongly recorded as clinical cases. Thus, the incidence of Staph. aureus mastitis is likely too low, and the genetic correlation between Staph. aureus mastitis and LASCC may therefore be underestimated in the present study. The results for the remaining pathogens were as expected, smallest for E. coli and larger but similar for Strep. dysgalactiae, Strep. uberis, and CNS. Selection for lower LASCC is expected to decrease the incidence of pathogen-specific mastitis, especially for Strep. uberis, Strep. dysgalactiae, and CNS and, to a lesser extent, for Staph. aureus and E. coli. Data recording should preferably be improved, and economic weights for the pathogen-specific mastitis traits should be estimated before implementing an udder health index that includes pathogen-specific mastitis traits.

Genetic parameters for pathogen-specific mastitis resistance in Danish Holstein Cattle.

The objective of this study was to estimate heritabilities for and genetic correlations among different pathogen-specific mastitis traits. The traits were unspecific mastitis, which is all mastitis treatments regardless of the causative pathogen as well as mastitis caused by Streptococcus dysgalactiae, Escherichia coli, coagulase-negative staphylococci (CNS), Staphylococcus aureus and Streptococcus uberis. Also groups of pathogens were investigated, Gram-negative v. Gram-positive and contagious v. environmental pathogens. Data from 168 158 Danish Holstein cows calving first time between 1998 and 2006 were used in the analyses. Variances and covariances were estimated using uni- and bivariate threshold models via Gibbs sampling. Posterior means of heritabilities of pathogen-specific mastitis were lower than the heritability of unspecific mastitis, ranging from 0.035 to 0.076 for S. aureus and S. uberis, respectively. The heritabilities of groups of pathogen ranged from 0.053 to 0.087. Genetic correlations among the pathogen-specific mastitis traits ranged from 0.45 to 0.77. These estimates tended to be lowest for bacteria eliciting very different immune responses, which can be considered as the overall pleiotropic effect of genes affecting resistance to a specific pathogen, and highest for bacteria sharing characteristics regarding immune response. The genetic correlations between the groups of pathogens were high, 0.73 and 0.83. Results showed that the pathogen-specific traits used in this study should be considered as different traits. Genetic evaluation for pathogen-specific mastitis resistance may be beneficial despite lower heritabilities than unspecific mastitis because a pathogen-specific mastitis trait is a direct measure of an udder infection, and because the cost of a mastitis case caused by different pathogens has been shown to differ greatly. Sampling bias may be present because there were not pathogen information on all mastitis treatments and because some farms do not record pathogen information. Therefore, improved recording of pathogen information and mastitis treatments in general is critical for a successful genetic evaluation of udder health. Also, economic values have to be specified for each pathogen-specific trait separately.

Pathogen-specific effects of quantitative trait loci affecting clinical mastitis and somatic cell count in Danish Holstein cattle.

The aim of this study was to investigate whether quantitative trait loci (QTL) affecting the risk of clinical mastitis (CM) and QTL affecting somatic cell score (SCS) exhibit pathogen-specific effects on the incidence of mastitis. Bacteriological data on mastitis pathogens were used to investigate pathogen specificity of QTL affecting treatments of mastitis in first parity (CM1), second parity (CM2), and third parity (CM3), and QTL affecting SCS. The 5 most common mastitis pathogens in the Danish dairy population were analyzed: Streptococcus dysgalactiae, Escherichia coli, coagulase-negative staphylococci, Staphylococcus aureus, and Streptococcus uberis. Data were analyzed using 2 approaches: an independence test and a generalized linear mixed model. Three different data sets were used to investigate the effect of data sampling: all samples, only samples that were followed by antibiotic treatment, and samples from first-crop daughters only. The results showed with high certainty that 2 QTL affecting SCS exhibited pathogen specificity against Staph. aureus and E. coli, respectively. The latter result might be explained by a pleiotropic QTL that also affects CM2 and CM3. Less certain results were found for QTL affecting CM. A QTL affecting CM1 was found to be specific against Strep. dysgalactiae and Staph. aureus, a QTL affecting CM2 was found to be specific against E. coli, and finally a QTL affecting CM3 was found to be specific against Staph. aureus. None of the QTL analyzed was found to be specific against coagulase-negative staphylococci and Strep. uberis. Our results show that particular mastitis QTL are highly likely to exhibit pathogen-specificity. However, the results should be interpreted carefully because the results are sensitive to the sampling method and method of analysis. Field data were used in this study. These kind of data may be heavily biased because there is no standard procedure for collecting milk samples for bacteriological analysis in Denmark. Furthermore, using only the mean SCS from d 10 to 180 after parturition may lead to truncated effects of SCS-QTL when samples collected after d 180 are used. Additionally, repeated samples were used, which could boost the difference in incidence of pathogens between daughters of sires inheriting the positive and negative QTL allele, respectively. However, the magnitude of these effects in this study is unclear.

Studies of the MHC class I molecules of veto-active and veto-inactive lectin-stimulated spleen cell populations.

Mouse spleen cells activated for three days with ConA, but not with PHA and LPS, were found to possess strong veto activity. Thus, ConA-activated spleen cells were capable of preventing a cytotoxic T cell response generated in MLC against the H-2 haplotype of the ConA-activated cells. Radiolabelling and chemical cross-linking of veto-active and veto-inactive cells, followed by immunoprecipitation of H-2, class I antigens, and analyses of the precipitates by one and two dimensional SDS PAGE were performed. By these procedures we were unable to demonstrate qualitative and quantitative differences between precipitates of veto-active and veto-inactive cell populations.