Effects of a mastitis J5 bacterin vaccination on the productive performance of dairy cows: An observational study using propensity score matching techniques.

Inferring causal effects between variables when utilizing observational data is challenging due to confounding factors not controlled through a randomized experiment. Propensity score matching can decrease confounding in observational studies and offers insights about potential causal effects of prophylactic management interventions such as vaccinations. The objective of this study was to determine potential causality and impact of vaccination with an Escherichia coli J5 bacterin on the productive performance of dairy cows applying propensity score matching techniques to farm-recorded (e.g., observational) data. Traits of interest included 305-d milk yield (MY305), 305-d fat yield (FY305), 305-d protein yield (PY305), and somatic cell score (SCS). Records from 6,418 lactations generated by 5,121 animals were available for the analysis. Vaccination status of each animal was obtained from producer-recorded information. Confounding variables considered were herd-year-season groups (56 levels), parity (5 levels: 1, 2, 3, 4, and ≥5), and genetic quartile groups (4 levels: top 25% through bottom 25%) derived from genetic predictions for MY305, FY305, PY305, and SCS, as well as for the genetic susceptibility to mastitis. A logistic regression model was applied to estimate the propensity score (PS) for each cow. Subsequently, PS values were used to form pairs of animals (1 vaccinated with 1 unvaccinated control), depending on their PS similarities (difference in PS values of cows within a match required to be <20% of 1 standard deviation of the logit of PS). After the matching process, 2,091 pairs of animals (4,182 records) remained available to infer the causal effects of vaccinating dairy cows with the E. coli J5 bacterin. Causal effects estimation was performed using 2 approaches: simple matching and a bias-corrected matching. According to the PS methodology, causal effects of vaccinating dairy cows with a J5 bacterin on their productive performance were identified for MY305. The simple matched estimator suggested that vaccinated cows produced 163.89 kg more milk over an entire lactation when compared with nonvaccinated counterparts, whereas the bias-corrected estimator suggested that such increment in milk production was of 150.48 kg. Conversely, no causal effects of immunizing dairy cows with a J5 bacterin were identified for FY305, PY305, or SCS. In conclusion, the utilization of PS matching techniques applied to farm-recorded data was feasible and allowed us to identify that vaccination with an E. coli J5 bacterin relates to an overall milk production increment without compromising milk quality.

Indirect genomic predictions for milk yield in crossbred Holstein-Jersey dairy cattle.

The objective of this study was to predict genomic breeding values for milk yield of crossbred dairy cattle under different scenarios using single-step genomic BLUP (ssGBLUP). The data set included 13,880,217 milk yield measurements on 6,830,415 cows. Genotypes of 89,558 Holstein, 40,769 Jersey, and 22,373 Holstein-Jersey crossbred animals were used, of which all Holstein, 9,313 Jersey, and 1,667 crossbred animals had phenotypic records. Genotypes were imputed to 45K SNP markers. The SNP effects were estimated from single-breed evaluations for Jersey (JE), Holstein (HO) and crossbreds (CROSS), and multibreed evaluations including all Jersey and Holstein (JE_HO) or approximately equal proportions of Jersey, Holstein, and crossbred animals (MIX). Indirect predictions (IP) of the validation animals (358 crossbred animals with phenotypes excluded from evaluations) were calculated using the resulting SNP effects. Additionally, breed proportions (BP) of crossbred animals were applied as a weight when IP were estimated based on each pure breed. The predictive ability of IP was calculated as the Pearson correlation between IP and phenotypes of the validation animals adjusted for fixed effects in the model. Regression of adjusted phenotypes on IP was used to assess the inflation of IP. The predictive ability of IP for CROSS, JE, HO, JE_HO, and MIX scenario was 0.50, 0.50, 0.47, 0.50, and 0.46, respectively. Using BP was the least successful, with a predictive ability of 0.32. The inflation of the IP for crossbred animals using CROSS, JE, HO, JE_HO, MIX, and BP scenarios were 1.17, 0.65, 0.55, 0.78, 1.00, and 0.85, respectively. The IP of crossbred animals can be predicted using single-step GBLUP under a scenario that includes purebred genotypes.

Genomic evaluation for wellness traits in US Jersey cattle.

The number of Jersey cows in the United States has been steadily increasing in recent years according to Council on Dairy Cattle Breeding statistics. To help producers reduce the risk of health disorders in their Jersey animals, Zoetis has developed genomic predictions for wellness traits in Jersey cattle using producer-recorded data. The traits included mastitis (MAST), metritis, retained placenta, displaced abomasum (DA), ketosis, lameness, and milk fever in cows and respiratory disease, scours, and calf livability (DEAD) in calves. Phenotypic data on health events, pedigree, and genotypes were collected directly from producers upon obtaining their permission. Each trait was defined as a binary event, having a value of 1 if an animal has been recorded with a disorder and 0 otherwise. The number of phenotypic records ranged from 216,166 for DA to 628,958 for MAST for cow traits and from 186,505 for scours to 380,429 for DEAD for calf traits. The number of genotyped animals was 41,271. All traits were analyzed using a univariate threshold animal model. The model for cow wellness traits included the fixed effect of parity and random effects of herd × year × season of calving, animal, and permanent environment. The model for calf wellness traits included the fixed effect of year of birth × calving season × region and random effects of herd × year of birth and animal. A total of 45,163 SNP were used in genomic analyses. Animals genotyped with low-density chips were imputed to the required number of markers. All analyses were based on the single-step genomic BLUP. Heritabilities ranged from 0.061 for DA to 0.120 for lameness. Predicted transmitting abilities were expressed in percentage points as deviations from the average estimated probability of a disorder in the base population. Reliabilities of genomic predicted transmitting abilities had average values between 32% (DA) and 51% (MAST and DEAD). The results indicate that a direct evaluation of cow and calf wellness traits under a genomic threshold model is feasible and offers predictions with average reliabilities comparable with other lowly heritable traits for Jersey cattle.

Genomic evaluation for calf wellness traits in Holstein cattle.

Reducing calf morbidity and mortality is important for attaining financial sustainability and improving animal welfare on commercial dairy operations. Zoetis (Kalamazoo, MI) has developed genomic predictions for calf wellness traits in Holsteins that include calf respiratory disease (RESP; recorded between 0 and 365 d of age), calf scours (DIAR; recorded between 2 and 50 d of age), and calf livability (DEAD; recorded between 2 and 365 d of age). Phenotype and pedigree data were from commercial dairies and provided directly by producers upon obtaining their permission. The number of records ranged from 741,484 for DIAR to 1,926,261 for DEAD. The number of genotyped animals was 325,025. All traits were analyzed using a univariate threshold animal model including fixed effect of year of birth × calving season × region, and random effects of herd × year of birth and animal. A total of 45,425 SNP were used in genomic analyses. Animals genotyped with low-density chips were imputed to the required number of SNP. All analyses were conducted using single-step genomic BLUP implementing the "algorithm for proven and young" (APY) animals designed to accommodate very large numbers of genotypes. Estimated heritabilities were 0.042, 0.045, and 0.060 for RESP, DIAR, and DEAD, respectively. The genomic predicted transmitting abilities ranged between -8.0 and 24.0, -11.5 and 28.5, and -6.5 to 22.8 for RESP, DIAR, and DEAD, respectively. Reliabilities of breeding values were obtained by approximation based on partitioning of a function of reliability into contributions from records, pedigree, and genotypes, where the genotype contribution was approximated using the diagonal value of the genomic relationship matrix. The average reliabilities for the genotyped animals were 41.9, 42.6, and 47.3% for RESP, DIAR, and DEAD, respectively. Estimated genomic predicted transmitting abilities and reliabilities were approximately normally distributed for all analyzed traits. Approximated genetic correlations of calf wellness with Zoetis dairy wellness traits and traits included in the US national genetic evaluation were low to moderate. The results indicate that direct evaluation of calf wellness traits under a genomic threshold model is feasible and offers predictions with average reliabilities comparable to other lowly heritable traits. Genetic selection for calf wellness traits presents a compelling opportunity for dairy producers to help manage herd replacement costs and improve overall profitability.

Genomic heritability and genome-wide association analysis of anti-Müllerian hormone in Holstein dairy heifers.

Anti-Müllerian hormone (AMH) is an ovarian growth factor that plays an important role in regulation of ovarian follicle growth. The objectives of this study were to estimate the genomic heritability of AMH and identify genomic regions associated with AMH production in a genome-wide association (GWA) analysis. Concentrations of AMH were determined in 2,905 dairy Holstein heifers genotyped using the Zoetis medium density panel (Zoetis Inclusions, Kalamazoo, MI) with 54,519 single nucleotide polymorphism (SNP) markers remaining after standard genotype quality control edits. A linear mixed model was used to model the random effects of sampling day and genomics on the logarithm of AMH. The genomic heritability (± standard error of the mean) of AMH was estimated to be 0.36 ± 0.03. Our GWA analysis inferred significant associations between AMH and 11 SNP markers on chromosome 11 and 1 SNP marker on chromosome 20. Annotated genes with significant associations were identified using the Ensembl genome database (version 88) of the cow genome (version UMD 3.1; https://www.ensembl.org/biomart). Gene set enrichment analysis revealed that 2 gene ontology (GO) terms were significantly enriched in the list of candidate genes: G-protein coupled receptor signaling pathway (GO:0007186) and the detection of chemical stimulus involved in sensory perception (GO:0050907). The estimated high heritability and previously established associations between AMH and ovarian follicular reserve, fertility, longevity, and superovulatory response in cattle implies that AMH could be used as a biomarker for genetic improvement of reproductive potential.

Development of genetic and genomic evaluation for wellness traits in US Holstein cows.

In March 2016, Zoetis Genetics offered the first commercially available evaluation for wellness traits of Holstein dairy cattle. Phenotypic data on health events, pedigree, and genotypes were collected directly from producers upon obtaining their permission. Among all recorded health events, 6 traits were chosen to be included in the evaluation: mastitis, metritis, retained placenta, displaced abomasum, ketosis, and lameness. Each trait was defined as a binary event, having a value of 1 if a cow has been recorded with a disorder at any point during the lactation and zero otherwise. The number of phenotypic records ranged from 1.8 million for ketosis to 4.1 million for mastitis. Over 14 million pedigree records and 114,216 genotypes were included in the evaluation. All traits were analyzed using univariate threshold animal model with repeated observations, including fixed effect of parity and random effects of herd by year by season of calving, animal, and permanent environment. A total of 45,425 single nucleotide polymorphisms were used in the genomic analyses. Animals genotyped with low-density chips were imputed to the required number of single nucleotide polymorphisms. All analyses were based on the single-step genomic BLUP, a method that combines phenotype, pedigree, and genotype information. Predicted transmitting abilities were expressed in percentage points as a difference from the average estimated probability of a disorder in the base population. Reliabilities of breeding values were obtained by approximation based on partitioning of a function of reliability into contributions from records, pedigree, and genotypes. Reliabilities of genomic predicted transmitting abilities for young genotyped and pedigreed females without recorded health events had average values between 50.2% (displaced abomasum) and 51.9% (mastitis). Genomic predictions for wellness traits can provide new information about an animal's genetic potential for health and new selection tools for dairy wellness improvement.

Evaluation of inbreeding depression in Holstein cattle using whole-genome SNP markers and alternative measures of genomic inbreeding.

The effects of increased pedigree inbreeding in dairy cattle populations have been well documented and result in a negative impact on profitability. Recent advances in genotyping technology have allowed researchers to move beyond pedigree analysis and study inbreeding at a molecular level. In this study, 5,853 animals were genotyped for 54,001 single nucleotide polymorphisms (SNP); 2,913 cows had phenotypic records including a single lactation for milk yield (from either lactation 1, 2, 3, or 4), reproductive performance, and linear type conformation. After removing SNP with poor call rates, low minor allele frequencies, and departure from Hardy-Weinberg equilibrium, 33,025 SNP remained for analyses. Three measures of genomic inbreeding were evaluated: percent homozygosity (FPH), inbreeding calculated from runs of homozygosity (FROH), and inbreeding derived from a genomic relationship matrix (FGRM). Average FPH was 60.5±1.1%, average FROH was 3.8±2.1%, and average FGRM was 20.8±2.3%, where animals with larger values for each of the genomic inbreeding indices were considered more inbred. Decreases in total milk yield to 205d postpartum of 53, 20, and 47kg per 1% increase in FPH, FROH, and FGRM, respectively, were observed. Increases in days open per 1% increase in FPH (1.76 d), FROH (1.72 d), and FGRM (1.06 d) were also noted, as well as increases in maternal calving difficulty (0.09, 0.03, and 0.04 on a 5-point scale for FPH, FROH, and FGRM, respectively). Several linear type traits, such as strength (-0.40, -0.11, and -0.19), rear legs rear view (-0.35, -0.16, and -0.14), front teat placement (0.35, 0.25, 0.18), and teat length (-0.24, -0.14, and -0.13) were also affected by increases in FPH, FROH, and FGRM, respectively. Overall, increases in each measure of genomic inbreeding in this study were associated with negative effects on production and reproductive ability in dairy cows.

New ischemic brain lesions on diffusion-weighted MRI after carotid artery stenting with filter protection: frequency and relationship with plaque morphology.

BACKGROUND AND PURPOSE: CAS carries an inherent risk of distal cerebral embolization, precipitating new brain ischemic lesions and neurologic symptoms. Our purpose was to evaluate the frequency of new ischemic lesions found on DWI after protected CAS placement and to determine its association with plaque morphology. MATERIALS AND METHODS: Fifty patients (mean age 65.13 ± 7.08 years) with moderate and severe internal carotid artery stenosis underwent CAS with distal filter protection. Fibrolipid and fibrocalcified plaque morphology was determined by sonography according to the relative contribution of echogenic and echolucent material, and by multisection CT using plaque attenuation. There were 46.81% of patients with fibrolipid and 53.19% with fibrocalcified plaques. DWI was performed before and 24 hours after CAS. RESULTS: Seven (14.89%) patients showed new lesions. Four (8.51%) had 6 new lesions inside the treated vascular territory. Three had a single lesion and 1 patient had 3 lesions (mean: 1.5 ± 1). Most lesions (66.66%) were subcortical, with a mean diameter of 9 mm (range 5-15 mm). All lesions occurred in the area supplied by the middle cerebral artery and were clinically silent. A significant relationship was found between plaque morphology and the appearance of new lesions. Patients with fibrolipid plaques had a significantly higher number of new lesions compared with patients with fibrocalcified plaques (P = .041). The absolute risk of new lesions in the fibrolipid group was 18.18%. CONCLUSIONS: New ischemic lesions were observed in the treated vascular territory in 8.51% of patients. The appearance of new ischemic lesions was significantly related to the plaque morphology. Fibrolipid plaques were associated with higher numbers of new lesions.

A prototype national cattle evaluation for sustained reproductive success in Hereford cattle.

The objective of this research was to develop a prototype system for national cattle evaluation that would facilitate selection for improved fertility of daughters from Hereford sires. Raw data for this analysis were the birth dates of calves as reported by breeders to the American Hereford Association. Records from females entered this analysis with the reporting of a birth date for their first calf. At that time, females were required to be in contemporary groups of at least 3 animals and to have at least 2 additional paternal half-sibs also represented in the data. To explicitly define "sustained reproductive success," the philosophy taken was that a female that maintained a calving interval of 425 d or less would be considered successful. Females failing to meet this criterion were considered to be at the end of their successful lifetime. Data were analyzed using methodology for survival analysis with grouped data. Fixed contemporary groups were modeled as being time dependent, reflecting the females exposed for breeding in the same herd-year-season. Sire effects were time independent and considered random. Also included in the analysis were time-independent covariates for maternal weaning weight and total maternal calving ease from the national cattle evaluation of the American Hereford Association. Records from females still successfully in production at the time of this analysis, those that were transferred, those with calving intervals less than 280 d, and those that were successful until becoming donor dams for embryo transfer were considered censored. A total of 36,866 females contributed to this analysis, with 14,143 of these having censored records. The median number of females in a contemporary group was 6. A total of 3,323 sires had daughters with records. The median number of daughters per sire was 7. Heritability of sustained reproductive success on the underlying scale estimated from these data was approximately 0.05. Additional data accumulated over time will improve this genetic evaluation. Sustained reproductive success is important to the commercial beef industry, and results from this evaluation are expected to enhance the assessment of economic value of Hereford seedstock.

Impacts of using inbred animals in studies for detection of quantitative trait loci.

Effects of utilizing inbred and noninbred family structures in experiments for detection of quantitative trait loci (QTL) were compared in this simulation study. Simulations were based on a general pedigree design originating from 2 unrelated sires. A variance component approach of mapping QTL was applied to simulated data that reflected common family structures from dairy populations. Five different family structures were considered: FS0 without inbreeding, FS1 with an inbred sire from an aunt-nephew mating, FS2 with an inbred sire originating from a half-sib mating, FS3 and FS4 based on FS2 but containing an increased number of offspring of the inbred sire (FS3), and another extremely inbred sire with its final offspring (FS4). Sixty replicates each of the 5 family structures in 2 simulation scenarios each were analyzed to provide a praxis-like situation of QTL analysis. The largest proportion of QTL position estimates within the correct interval of 3 cM, best test statistic profiles and the smallest average bias were obtained from the pedigrees described by FS4 and FS2. The approach does not depend on the kind and number of genetic markers. Inbreeding is not a recommended practice for commercial dairy production because of possible inbreeding depression, but inbred animals and their offspring that already exist could be advantageous for QTL mapping, because of reduced genetic variance in inbred parents.

Using conformation traits to improve reliability of genetic evaluation for herd life based on survival analysis.

Genetic evaluation for herd life based on survival analysis utilizes information available on all animals, dead (uncensored) and alive (censored), but the reliability of bulls' breeding values depends only on the number of uncensored daughters. Therefore, information on correlated conformation traits scored on daughters during their first lactation may be essential for the evaluation of young bulls with mostly censored daughters. Currently available programs for genetic evaluation based on survival analysis cannot combine indirect information on conformation traits with direct information on herd life, nor can they estimate genetic covariances between herd life and conformation traits. In this study, an alternative approach has been developed and tested using data on Swiss Simmental and Red & White cattle. Genetic covariances were approximated using breeding values for herd life from a survival analysis and BLUP breeding values for 26 linear conformation traits from a separate multivariate analysis. An index combining direct breeding values for herd life and indirect breeding values obtained from conformation traits was constructed. The relative weighting of both information sources varied depending on the amount of available information. The maximum reliability based only on conformation traits was 0.64. Except for old bulls with >100 uncensored daughters, the combined reliability was always higher than the direct reliability from survival analysis.

Implementation of a routine genetic evaluation for longevity based on survival analysis techniques in dairy cattle populations in Switzerland.

Genetic evaluation of sires for functional longevity of their daughters based on survival analysis has been implemented in the populations of Braunvieh, Simmental, and Holstein cattle in Switzerland. A Weibull mixed sire-maternal grandsire survival model was used to estimate breeding values of sires with data on cows that calved since April 1, 1980. Data on Braunvieh and Simmental cows included about 1.1 million records, data on Holstein cows comprised about 220,000 records. Data contained approximately 20 to 24% right-censored records and 6 to 9% left-truncated records. Besides the random sire and maternal grandsire effects, the model included effects of herd-year-season, age at first calving, parity, stage of lactation, alpine pasturing (Braunvieh and Simmental), and relative milk yield and relative fat and protein percentage within herd to account for culling for production. Heritability of functional longevity, estimated on a subset of data including approximately 150,000 animals, were 0.181, 0.198, and 0.184 for Braunvieh, Simmental, and Holstein, respectively. Breeding values were estimated for all sires with at least six daughters or three granddaughters in the data. Breeding values of sires are expressed in months of functional productive life and published in sire catalogs along with breeding values for production traits.

Genetic evaluation for length of productive life with censored records.

This study was conducted to investigate the impact of censoring on the accuracy of sire evaluation for the length of productive life estimated by means of survival analysis using simulated and real dairy cattle data from the Swiss Braunvieh population. Data were simulated under a Weibull model with two fixed effects and a random sire effect with a sire variance of 0.04. Two different family structures investigated were 1000 sires with 10 daughters each and 200 sires with 50 daughters each. Sires were assumed to be related through their sires. The reference data were generated assuming no censoring. Sire effects were estimated from the reference data with and without considering the relationships among sires and referred to as the estimated transmitting abilities (ETA) of sires. The impact of censoring on accuracy of ETA and ranking of sires was investigated by computing rank correlations among true and estimated sire effects and among estimated sire effects from the reference data and from several different data files with increased proportion of censored records. Estimated transmitting abilities were generally more accurate with a large number of daughters. The rank correlations among the ETA of sires from the data with censored records and the ETA from the reference data decreased with an increased proportion of censored records. Considering relationships among sires resulted in higher rank correlations when the proportion of censored records was large. With 50 daughters per sire, accuracy of 70% can be achieved approximately 2 yr after first calving of the daughters with about 50% censored records. With the real data, a rank correlation with the ETA of sires from the reference data of 0.70 to 0.80 can be achieved with about 65% of records censored and about 2.5 yr after the first calving of the youngest daughters of the sires.

Association of growth hormone loci with milk yield traits in Holstein bulls.

A pedigree analysis was used to investigate the association of bovine growth hormone loci with milk production traits of Holstein cattle. Holstein bulls were typed for three bovine growth hormone loci located in exon V, intron C, and the 3' region of the gene. Phenotypic data were daughter yield deviations for milk, fat, and protein yields and for fat and protein percentages. Analysis of linkage across families was applied to the data using one or two bovine growth hormone loci as markers linked to a putative biallelic quantitative trait locus. Estimated parameters were allele frequency, genotypic means, within-genotype standard deviation of a putative quantitative trait locus, and recombination fraction between the markers and the quantitative trait locus. Parameters were estimated by maximum likelihood techniques. The estimated frequency of the quantitative trait locus allele that decreased the value of the phenotype ranged from 0.1 for milk yield to 0.6 for protein yield. The estimated effect of an allele substitution at the quantitative trait locus, given in phenotypic standard deviation units, ranged from 0.75 for fat percentage to 1.6 for milk yield. The standard deviation within genotype ranged from 0.67 for fat yield to 0.87 for milk yield. The estimated recombination fraction was close to zero for protein percentage, indicating physical linkage between a quantitative trait locus affecting the trait and the bovine growth hormone loci.

Analysis of productive life in Swiss brown cattle.

An analysis of productive life of Swiss Brown cattle was performed using a mixed survival model based on Cox regression. Data included 52,862 daughters of 297 sires. The length of productive life was observed from May 1, 1985 through August 15, 1995. Records on cows that were still alive in the end of study (32.4%) were treated as censored. The probability of being culled (hazard) was defined as a product of a baseline hazard function and a function of explanatory variables. In addition to sire effects, the model included effects of age at first calving and the time-dependent variables herd by year, lactation number, stage of lactation, and milk production within the herd to account for culling because of low production. Solutions for fixed effects indicated a higher probability of being culled for primiparous cows, for cows in the end stage of lactation, and for cows with low production. The impact of censoring on the accuracy of estimation was investigated by computing the rank correlations between the estimated transmitting abilities (ETA) of sires using a simplified model from uncensored data (reference) and the ETA from several different data files with an increased proportion of censored records. The rank correlations among sire ETA decreased as number of daughters per sire decreased and as the proportion of censored records increased. The maximum number of censored records that is acceptable to obtain accurate results is 30 to 40%. The acceptable proportion of censored records would be higher if the reference ETA were obtained on a larger data file using daughters of old sires.