Genetic evaluations and genome-wide association studies for specific digital dermatitis diagnoses in dairy cows considering genotype × housing system interactions.

The present study aimed to use detailed phenotyping for the claw disorder digital dermatitis (DD) considering specific DD stages in 2 housing systems (conventional cubicle barns [CON] and compost-bedded pack barns [CBPB]) to infer possible genotype × housing system interactions. The DD stages included 2,980 observations for the 3 traits DD-sick, DD-acute, and DD-chronic from 1,311 Holstein-Friesian and 399 Fleckvieh-Simmental cows. Selection of the 5 CBPB and 5 CON herds was based on a specific protocol to achieve a high level of herd similarity with regard to climate, feeding, milking system, and location, but with pronounced housing-system differences. Five other farms had a "mixed system" with 2 subherds, one representing CBPB and the other one CON. The CBPB system was represented by 899 cows (1,530 observations), and 811 cows (1,450 observations) represented the CON system. The average disease prevalence was 20.47% for DD-sick, 13.88% for DD-acute, and 5.34% for DD-chronic, with a higher prevalence in CON than in CBPB. After quality control of 50K genotypes, 38,495 SNPs from 926 cows remained for the ongoing genomic analyses. Genetic parameters for DD-sick, DD-acute, and DD-chronic were estimated by applying single-step approaches for single-trait repeatability animal models considering the whole dataset, and separately for the CON and CBPB subsets. Genetic correlations between same DD traits from different housing systems, and between DD-sick, DD-chronic, and DD-acute, were estimated via bivariate animal models. Heritabilities based on the whole dataset were 0.16 for DD-sick, 0.14 for DD-acute, and 0.11 for DD-chronic. A slight increase of heritabilities and genetic variances was observed in CON compared with the "well-being" CBPB system, indicating a stronger genetic differentiation of diseases in a more challenging environment. Genetic correlations between same DD traits recorded in CON or CBPB were close to 0.80, disproving obvious genotype × housing system interactions. Genetic correlations among DD-sick, DD-acute and DD-chronic ranged from 0.58 to 0.81. SNP main effects and SNP × housing system interaction effects were estimated simultaneously via GWAS, considering only the phenotypes from genotyped cows. Ongoing annotations of potential candidate genes focused on chromosomal segments 100 kb upstream and downstream from the significantly associated candidate SNP. GWAS for main effects indicated heterogeneous Manhattan plots especially for DD-acute and DD-chronic, indicating particularities in disease pathogenesis. Nevertheless, a few shared annotated potential candidate genes, that is, METTL25, AFF3, PRKG1, and TENM4 for DD-sick and DD-acute, were identified. These genes have direct or indirect effects on disease resistance or immunology. For the SNP × housing system interaction, the annotated genes ASXL1 and NOL4L on BTA 13 were relevant for DD-sick and DD-acute. Overall, the very similar genetic parameters for the same traits in different environments and negligible genotype × housing system interactions indicate only minor effects on genetic evaluations for DD due to housing-system particularities.

Genome-wide association and functional genomic analyses for various hoof health traits in North American Holstein cattle.

Hoof diseases are a major welfare and economic issue in the global dairy cattle production industry, which can be minimized through improved management and breeding practices. Optimal genetic improvement of hoof health could benefit from a deep understanding of the genetic background and biological underpinning of indicators of hoof health. Therefore, the primary objectives of this study were to perform genome-wide association studies, using imputed high-density genetic markers data from North American Holstein cattle, for 8 hoof-related traits: digital dermatitis, sole ulcer, sole hemorrhage, white line lesion, heel horn erosion, interdigital dermatitis, interdigital hyperplasia, and toe ulcer, and a hoof health index. De-regressed estimated breeding values from 25,580 Holstein animals were used as pseudo-phenotypes for the association analyses. The genomic quality control, genotype phasing, and genotype imputation were performed using the PLINK (version 1.9), Eagle (version 2.4.1), and Minimac4 software, respectively. The functional genomic analyses were performed using the GALLO R package and the DAVID platform. We identified 22, 34, 14, 22, 28, 33, 24, 43, and 15 significant markers for digital dermatitis, heel horn erosion, interdigital dermatitis, interdigital hyperplasia, sole hemorrhage, sole ulcer, toe ulcer, white line lesion disease, and the hoof health index, respectively. The significant markers were located across all autosomes, except BTA10, BTA12, BTA20, BTA26, BTA27, and BTA28. Moreover, the genomic regions identified overlap with various previously reported quantitative trait loci for exterior, health, meat and carcass, milk, production, and reproduction traits. The enrichment analyses identified 44 significant gene ontology terms. These enriched genomic regions harbor various candidate genes previously associated with bone development, metabolism, and infectious and immunological diseases. These findings indicate that hoof health traits are highly polygenic and influenced by a wide range of biological processes.

Continuous activation of the IL-17F driven inflammatory pathway in acute and chronic digital dermatitis lesions in dairy cattle.

Objectives of the present study were to get a deeper insight into the course of the inflammatory pathways of digital dermatitis lesions in dairy cattle by investigating the gene expression patterns throughout the different clinical stages (M0 to M4.1) of the disease. Normal skin samples (M0) were used as a reference for comparing the gene expression levels in the other M-stages through RNA Seq-technology. Principal component analysis revealed a distinct gene expression pattern associated with digital dermatitis lesions in comparison to healthy skin with a further clustering of the acute M1, M2 and M4.1 stages versus the chronic M3 and M4 stages. The majority of the up-and downregulated genes in the acute and chronic stages can be placed into a common 'core' set of genes involved in inflammation, such as A2ML1, PI3, CCL11 and elafin-like protein, whereas the most downregulated genes included keratins and anti-inflammatory molecules such as SCGB1D and MGC151921. Pathway analysis indicated the activation of the pro-inflammatory IL-17 signaling pathway in all the M stages through the upregulation of IL-17F. These results indicate that digital dermatitis is associated with an excessive inflammatory immune response concomitant with a disrupted skin barrier and impaired wound repair mechanism. Importantly, despite their macroscopically healed appearance, a significant inflammatory response (Padj < 0.05) was still measurable in the M3 and M4 lesions, potentially explaining the frequent re-activation of such lesions.

On the origin of the genetic variation in infectious disease prevalence: Genetic analysis of disease status versus infections for Digital Dermatitis in Dutch dairy cattle.

The purpose of this study was to investigate the origin of the genetic variation in the prevalence of bovine digital dermatitis (DD) by comparing a genetic analysis of infection events to a genetic analysis of disease status. DD is an important endemic infectious disease affecting the claws of cattle. For disease status, we analysed binary data on individual disease status (0,1; indicating being free versus infected), whereas for infections, we analysed binary data on disease transmission events (1,0; indicating becoming infected or not). The analyses of the two traits were compared using cross-validation. The analysis of disease status captures a combination of genetic variation in disease susceptibility and the ability of individuals to recover, whereas the analysis of infections captures genetic variation in susceptibility only. Estimated genetic variances for both traits indicated substantial genetic variation. The GEBV for disease status and infections correlated with only 0.60, indicating that both models indeed capture distinct information. Together, these results suggest the presence of genetic variation not only in disease susceptibility, but also in the ability of individuals to recover from DD. We argue that the presence of genetic variation in recovery implies that breeders should distinguish between infected individuals versus infectious individuals. This is because epidemiological theory shows that selection for recovery is effective only when it targets recovery from being infectious.

Oxytetracycline reduces inflammation and treponeme burden whereas vitamin D3 promotes ß-defensin expression in bovine infectious digital dermatitis.

Digital dermatitis (DD), a common ulcerative disease of the bovine foot causing lameness and reducing productivity and animal welfare, is associated with infection by spirochete Treponema bacteria. Topical tetracycline, the most common treatment, has inconsistent cure rates; therefore, new therapeutic options are needed. We compared effects of topical oxytetracycline and vitamin D3 on innate immunity in DD-affected skin. Cows with active DD lesions were treated topically with oxytetracycline or vitamin D3 and skin biopsies were collected from lesions. Tissue samples were examined histologically, transcriptional expression of pro-inflammatory cytokines, Toll-like receptors (TLRs), and host defense peptides assessed, and the presence of specific treponeme species determined. Effects of treatments at a mechanistic level were studied in a human keratinocyte model of treponeme infection. Oxytetracycline promoted hyperplastic scab formation in ulcerated DD lesions and decreased transcriptional expression of Cxcl-8 (neutrophil chemoattractant). Oxytetracycline also reduced numbers of Treponema phagedenis and T. pedis and enhanced Tlr2 mRNA expression. Vitamin D3 did not modify expression of cytokines or Tlrs, or bacterial loads, but enhanced transcription of tracheal antimicrobial peptide (Tap), a key bovine ß-defensin. Combing oxytetracycline and vitamin D3 provides complementary clinical benefits in controlling DD through a combination of antimicrobial, immunomodulatory, and pro-healing activities.

Genetic parameters and genomic breeding values for digital dermatitis in Holstein Friesian dairy cattle: host susceptibility, infectivity and the basic reproduction ratio.

BACKGROUND: For infectious diseases, the probability that an animal gets infected depends on its own susceptibility, and on the number of infectious herd mates and their infectivity. Together with the duration of the infectious period, susceptibility and infectivity determine the basic reproduction ratio of the disease ([Formula: see text]). [Formula: see text] is the average number of secondary cases caused by a typical infectious individual in an otherwise uninfected population. An infectious disease dies out when [Formula: see text] is lower than 1. Thus, breeding strategies that aim at reducing disease prevalence should focus on reducing [Formula: see text], preferably to a value lower than 1. In animal breeding, however, [Formula: see text] has received little attention. Here, we estimate the additive genetic variance in host susceptibility, host infectivity, and [Formula: see text] for the endemic claw disease digital dermatitis (DD) in Holstein Friesian dairy cattle, and estimate genomic breeding values (GEBV) for these traits. We recorded DD disease status of both hind claws of 1513 cows from 12 Dutch dairy farms, every 2 weeks, 11 times. The genotype data consisted of 75,904 single nucleotide polymorphisms (SNPs) for 1401 of the cows. We modelled the probability that a cow got infected between recordings, and compared four generalized linear mixed models. All models included a genetic effect for susceptibility; Models 2 and 4 also included a genetic effect for infectivity, while Models 1 and 2 included a farm*period interaction. We corrected for variation in exposure to infectious herd mates via an offset. RESULTS: GEBV for [Formula: see text] from the model that included genetic effects for susceptibility only had an accuracy of ~ 0.39 based on cross-validation between farms, which is very high given the limited amount of data and the complexity of the trait. Models with a genetic effect for infectivity showed a larger bias, but also a slightly higher accuracy of GEBV. Additive genetic standard deviation for [Formula: see text] was large, i.e. ~ 1.17, while the mean [Formula: see text] was 2.36. CONCLUSIONS: GEBV for [Formula: see text] showed substantial variation. The mean [Formula: see text] was only about one genetic standard deviation greater than 1. These results suggest that lowering DD prevalence by selective breeding is promising.

Genomic analysis of claw lesions in Holstein cows: Opportunities for genomic selection, quantitative trait locus detection, and gene identification.

Claw lesions are the third most important health issue in dairy cattle, after mastitis and reproductive disorders, and genomic selection is a key component for long-term improvement of claw health. The objectives of this study were to assess the feasibility of a genomic evaluation for claw health in French Holstein cows, explore possibilities to increase evaluation accuracy, and gain a better understanding of the genetic determinism of claw health traits. The data set consisted of 48,685 trimmed Holstein cows, including 9,646 that were genotyped; 478 genotyped sires were also used. Seven claw lesion traits were evaluated using BLUP, genomic BLUP, BayesC, and single-step genomic BLUP, and the accuracies obtained using these approaches were measured through a validation study. The BayesC approach was used to detect quantitative trait locus (QTL) regions associated with the 7 individual traits (digital dermatitis, heel horn erosion, interdigital hyperplasia, sole hemorrhage circumscribed, sole hemorrhage diffused, sole ulcer, and white line fissure) based on their Bayes factor. Annotated genes on these regions were reported. Genomic evaluation approaches generally did not allow for greater accuracies than BLUP, except for single-step genomic BLUP. Accuracies were moderate, but best and worst validation animals were correctly discriminated and showed significant differences in lesion frequencies. A total of 192 QTL regions were identified, including 13 with major evidence or involved for 2 of the traits. A high number of genes were present on these regions, and several had functions associated with the immune system. In particular, the EPYC gene is located close to a major evidence QTL for resistance to digital dermatitis that is also a QTL for interdigital hyperplasia (on chromosome 5, around 20.9 MB) and has been associated with Ehlers-Danlos syndrome in cattle. Genomic selection can be used to improve resistance to individual claw lesions, and several possibilities exist to improve accuracies of genomic evaluations.

A genome-wide association study for susceptibility and infectivity of Holstein Friesian dairy cattle to digital dermatitis.

Selection and breeding can be used to fight transmission of infectious diseases in livestock. The prevalence in a population depends on the susceptibility and infectivity of the animals. Knowledge on the genetic background of those traits would facilitate efficient selection for lower disease prevalence. We investigated the genetic background of host susceptibility and infectivity for digital dermatitis (DD), an endemic infectious claw disease in dairy cattle, with a genome-wide association study (GWAS), using either a simple linear mixed model or a generalized linear mixed model based on epidemiological theory. In total, 1,513 Holstein-Friesian cows of 12 Dutch dairy farms were scored for DD infection status and class (M0 to M4.1) every 2 wk for 11 times; 1,401 of these cows were genotyped with a 75k SNP chip. We performed a GWAS with a linear mixed model on 10 host disease status traits, and with a generalized linear mixed model with a complementary log-log link function (GLMM) on the probability that a cow would get infected between 2 scorings. With the GLMM, we fitted SNP effects for host susceptibility and host infectivity, while taking the variation in exposure of the susceptible cow to infectious herd mates into account. With the linear model we detected 4 suggestive SNP (false discovery rate < 0.20), 2 for the fraction of observations a cow had an active lesion on chromosomes 1 and 14, one for the fraction of observations a cow had an M2 lesion on at least one claw on chromosome 1 (the same SNP as for the fraction of observations with an active lesion), and one for the fraction of observations a cow had an M4.1 lesion on at least one claw on chromosome 10. Heritability estimates ranged from 0.09 to 0.37. With the GLMM we did not detect significant nor suggestive SNP. The SNP effects on disease status analyzed with the linear model had a correlation coefficient of only 0.70 with SNP effects on susceptibility of the GLMM, indicating that both models capture partly different effects. Because the GLMM better accounts for the epidemiological mechanisms determining individual disease status and for the distribution of the y-variable, results of the GLMM may be more reliable, despite the absence of suggestive associations. We expect that with an extended GLMM that better accounts for the full genetic variation in infectivity via the environment, the accuracy of SNP effects may increase.

Genetic parameters for hoof health traits estimated with linear and threshold models using alternative cohorts.

A national genetic evaluation program for hoof health could be achieved by using hoof lesion data collected directly by hoof trimmers. However, not all cows in the herds during the trimming period are always presented to the hoof trimmer. This preselection process may not be completely random, leading to erroneous estimations of the prevalence of hoof lesions in the herd and inaccuracies in the genetic evaluation. The main objective of this study was to estimate genetic parameters for individual hoof lesions in Canadian Holsteins by using an alternative cohort to consider all cows in the herd during the period of the hoof trimming sessions, including those that were not examined by the trimmer over the entire lactation. A second objective was to compare the estimated heritabilities and breeding values for resistance to hoof lesions obtained with threshold and linear models. Data were recorded by 23 hoof trimmers serving 521 herds located in Alberta, British Columbia, and Ontario. A total of 73,559 hoof-trimming records from 53,654 cows were collected between 2009 and 2012. Hoof lesions included in the analysis were digital dermatitis, interdigital dermatitis, interdigital hyperplasia, sole hemorrhage, sole ulcer, toe ulcer, and white line disease. All variables were analyzed as binary traits, as the presence or the absence of the lesions, using a threshold and a linear animal model. Two different cohorts were created: Cohort 1, which included only cows presented to hoof trimmers, and Cohort 2, which included all cows present in the herd at the time of hoof trimmer visit. Using a threshold model, heritabilities on the observed scale ranged from 0.01 to 0.08 for Cohort 1 and from 0.01 to 0.06 for Cohort 2. Heritabilities estimated with the linear model ranged from 0.01 to 0.07 for Cohort 1 and from 0.01 to 0.05 for Cohort 2. Despite a low heritability, the distribution of the sire breeding values showed large and exploitable variation among sires. Higher breeding values for hoof lesion resistance corresponded to sires with a higher prevalence of healthy daughters. The rank correlations between estimated breeding values ranged from 0.96 to 0.99 when predicted using either one of the 2 cohorts and from 0.94 to 0.99 when predicted using either a threshold or a linear model.

Single Nucleotide Polymorphisms in IL8 and TLR4 Genes as Candidates for Digital Dermatitis Resistance/Susceptibility in Holstein Cattle.

Relatedness between single nucleotide polymorphisms in IL8 and TLR4 genes and digital dermatitis resistance/susceptibility was investigated in seventy Holstein dairy cows. Animals were assigned into two groups, affected group (n = 35) and resistant group (n = 35) based on clinical signs and previous history of farm clinical records. Blood samples were collected for DNA extraction to ampliy fragments of 267-bp and 382-bp for IL8 and TLR4 genes, respectively. PCR-DNA sequencing revealed three SNPs in each of IL8 and TLR4 genes. The identified SNPs associated with digital dermatitis resistance were C94T, A220G, and T262A for IL8 and C118T for TLR4. However, the G349C and C355A SNPs in TLR4 gene were associated with digital dermatitis susceptibility. Chi-square analysis for comparison the distribution of all identified SNPs in both IL8 and TLR4 genes between resistant and affected animals showed no significant variation among the identified SNPs in IL8 gene. Meanwhile, there was a significant variation in case of TLR4 gene. As a pilot study, the present results revealed that identified SNPs in IL8 and TLR4 genes can be used as a genetic marker and predisposing factor for resistance/susceptibility to digital dermatitis in dairy cows. However, TLR4 gene may be a potential candidate for such disease.

A novel approach to probe host-pathogen interactions of bovine digital dermatitis, a model of a complex polymicrobial infection.

BACKGROUND: Polymicrobial infections represent a great challenge for the clarification of disease etiology and the development of comprehensive diagnostic or therapeutic tools, particularly for fastidious and difficult-to-cultivate bacteria. Using bovine digital dermatitis (DD) as a disease model, we introduce a novel strategy to study the pathogenesis of complex infections. RESULTS: The strategy combines meta-transcriptomics with high-density peptide-microarray technology to screen for in vivo-expressed microbial genes and the host antibody response at the site of infection. Bacterial expression patterns supported the assumption that treponemes were the major DD pathogens but also indicated the active involvement of other phyla (primarily Bacteroidetes). Bacterial genes involved in chemotaxis, flagellar synthesis and protection against oxidative and acidic stress were among the major factors defining the disease. CONCLUSIONS: The extraordinary diversity observed in bacterial expression, antigens and host antibody responses between individual cows pointed toward microbial variability as a hallmark of DD. Persistence of infection and DD reinfection in the same individual is common; thus, high microbial diversity may undermine the host's capacity to mount an efficient immune response and maintain immunological memory towards DD. The common antigenic markers identified here using a high-density peptide microarray address this issue and may be useful for future preventive measures against DD.

Investigating the genetic background of bovine digital dermatitis using improved definitions of clinical status.

Bovine digital dermatitis (DD) is an increasing claw health problem in all cattle production systems worldwide. The objective of this study was to evaluate the use of an improved scoring of the clinical status for DD via M-scores accounting for the dynamics of the disease; that is, the transitions from one stage to another. The newly defined traits were then subjected to a genetic analysis to determine the genetic background for susceptibility to DD. Data consisted of 6,444 clinical observations from 729 Holstein heifers in a commercial dairy herd, collected applying the M-score system. The M-score system is a classification scheme for stages of DD that allows a macroscopic scoring based on clinical inspections of the bovine foot, thus it describes the stages of lesion development. The M-scores were used to define new DD trait definitions with different complexities. Linear mixed models and logistic models were used to identify fixed environmental effects and to estimate variance components. In total, 68% of all observations showed no DD status, whereas 11% were scored as infectious for and affected by DD, and 21% of all observations exhibited an affected but noninfectious status. For all traits, the probability of occurrence and clinical status were associated with age at observation and period of observation. Risk of becoming infected increased with age, and month of observation significantly affected all traits. Identification of the optimal month concerning DD herd status was consistent for all trait definitions; the last month of the trial was identified. In contrast, months exhibiting the highest least squares means of transformed scores differed depending on trait definition. In this respect, traits that can distinguish between healthy, infectious, and noninfectious stages of DD can account for the infectious potential of the herd and can serve as an alert tool. Estimates of heritabilities of traits studied ranged between 0.19 (±0.11) and 0.52 (±0.17), revealing a tendency for higher values for more complex trait definitions. In terms of genetic selection, all trait definitions identified the best (i.e., most resistant) animals, but only the new trait definitions were able to distinguish between animals with average and high predispositions for DD. Considering repeated measurements resulted in heritability estimates ranging between 0.13 (±0.05) and 0.29 (±0.10).

Models for genetic evaluations of claw health traits in Spanish dairy cattle.

Genetic parameters of 7 claw health traits from Spanish dairy cattle were estimated and the predictive ability of linear and ordinal threshold models were compared and assessed. This study included data on interdigital and digital dermatitis (DE), sole ulcer (SU), white line disease (WL), interdigital hyperplasia (IH), interdigital phlegmon (IP), and chronic laminitis (CL) collected between July 2012 and June 2013 from 834 dairy herds visited by 21 trained trimmers. An overall claw disorder (OCD) was also considered an indicator the absence or the presence of at least 1 of the 6 disorders. Claw health traits were scored as categorical traits with 3 degrees of severity (nonaffected, mild, and severe disorder). Genetic parameters were estimated by fitting both a standard linear model and an ordinal threshold animal model. Around 21% of cows had at least 1 claw disorder, and the most frequent disorders were SU, DE, WL, and CL. Heritabilities of claw disorders estimated with a linear model ranged from 0.01 (IP) to 0.05 (OCD), whereas estimates from the ordinal threshold models ranged from 0.06 to 0.39 (for IP and IH, respectively). Repeatabilities of claw health estimated with the linear model varied from 0.03 to 0.18 and estimates with the ordinal threshold model ranged from 0.33 to 0.69. The global trait OCD was correlated with all disorders, except for IH and IP when the linear model was fitted. Two different genetic backgrounds of claw disorders were found. Digital dermatitis showed positive correlations with IH and IP, whereas SU was positively correlated with WL and CL. The predictive ability of the models was assessed using mean squared error and Pearson correlation between the real observation and the corresponding prediction using cross-validation. Regardless of the claw health status, the linear model led to smaller mean squared error. However, differences in predictive ability were found when predicting nonaffected and affected animals. For most traits, healthy cows were better predicted using the threshold model, whereas the linear model fitted affected cows better. Correlations between the observed data and corresponding predictions support those results ranging from 0.01 to 0.34. Claw health traits showed enough genetic variance to be included in the selection goal for Spanish Holsteins to select animals with less susceptibility to claw health problems, and we suggest the linear model for implementing genetic evaluations of claw heath traits.

Shotgun Metagenomic Sequencing Reveals Functional Genes and Microbiome Associated with Bovine Digital Dermatitis.

Metagenomic methods amplifying 16S ribosomal RNA genes have been used to describe the microbial diversity of healthy skin and lesion stages of bovine digital dermatitis (DD) and to detect critical pathogens involved with disease pathogenesis. In this study, we characterized the microbiome and for the first time, the composition of functional genes of healthy skin (HS), active (ADD) and inactive (IDD) lesion stages using a whole-genome shotgun approach. Metagenomic sequences were annotated using MG-RAST pipeline. Six phyla were identified as the most abundant. Firmicutes and Actinobacteria were the predominant bacterial phyla in the microbiome of HS, while Spirochetes, Bacteroidetes and Proteobacteria were highly abundant in ADD and IDD. T. denticola-like, T. vincentii-like and T. phagedenis-like constituted the most abundant species in ADD and IDD. Recruitment plots comparing sequences from HS, ADD and IDD samples to the genomes of specific Treponema spp., supported the presence of T. denticola and T. vincentii in ADD and IDD. Comparison of the functional composition of HS to ADD and IDD identified a significant difference in genes associated with motility/chemotaxis and iron acquisition/metabolism. We also provide evidence that the microbiome of ADD and IDD compared to that of HS had significantly higher abundance of genes associated with resistance to copper and zinc, which are commonly used in footbaths to prevent and control DD. In conclusion, the results from this study provide new insights into the HS, ADD and IDD microbiomes, improve our understanding of the disease pathogenesis and generate unprecedented knowledge regarding the functional genetic composition of the digital dermatitis microbiome.

Genome-wide association study for claw disorders and trimming status in dairy cattle.

Performing a genome-wide association study (GWAS) might add to a better understanding of the development of claw disorders and the need for trimming. Therefore, the aim of the current study was to perform a GWAS on claw disorders and trimming status and to validate the results for claw disorders based on an independent data set. Data consisted of 20,474 cows with phenotypes for claw disorders and 50,238 cows with phenotypes for trimming status. Recorded claw disorders used in the current study were double sole (DS), interdigital hyperplasia (IH), sole hemorrhage (SH), sole ulcer (SU), white line separation (WLS), a combination of infectious claw disorders consisting of (inter-)digital dermatitis and heel erosion, and a combination of laminitis-related claw disorders (DS, SH, SU, and WLS). Of the cows with phenotypes for claw disorders, 1,771 cows were genotyped and these cow data were used for the GWAS on claw disorders. A SNP was considered significant when the false discovery rate≤0.05 and suggestive when the false discovery rate≤0.20. An independent data set of 185 genotyped bulls having at least 5 daughters with phenotypes (6,824 daughters in total) for claw disorders was used to validate significant and suggestive SNP detected based on the cow data. To analyze the trait "trimming status" (i.e., the need for claw trimming), a data set with 327 genotyped bulls having at least 5 daughters with phenotypes (18,525 daughters in total) was used. Based on the cow data, in total 10 significant and 45 suggestive SNP were detected for claw disorders. The 10 significant SNP were associated with SU, and mainly located on BTA8. The suggestive SNP were associated with DS, IH, SU, and laminitis-related claw disorders. Three of the suggestive SNP were validated in the data set of 185 bulls, and were located on BTA13, BTA14, and BTA17. For infectious claw disorders, SH, and WLS, no significant or suggestive SNP associations were detected. For trimming status, 1 significant and 1 suggestive SNP were detected, both located close to each other on BTA15. Some significant and suggestive SNP were located close to SNP detected in studies on feet and leg conformation traits. Genes with major effects could not be detected and SNP associations were spread across the genome, indicating that many SNP, each explaining a small proportion of the genetic variance, influence claw disorders. Therefore, to reduce the incidence of claw disorders by breeding, genomic selection is a promising approach.

Sire predicted transmitting ability for conformation and yield traits and previous lactation incidence of foot lesions as risk factors for the incidence of foot lesions in Holstein cows.

The aims of the present study were (1) to investigate the repeatability of foot lesions [sole ulcers (SU), white line disease (WLD), and digital dermatitis (DD)] across multiple lactations, (2) to evaluate the effect of foot lesions on cow survivability and milk production across multiple lactations, and (3) to investigate the role of sire predicted transmitting ability (PTA) for conformation and production traits as risk factors for the incidence of SU, WLD, and DD. Data were collected from a dairy farm located in Cayuga County, New York. A total of 11,442 cows having first calved during the period from May 13, 2001, to March 26, 2012, were enrolled in the study. Data regarding sire genetic evaluations were obtained from DairyBulls.com (http://www.DairyBulls.com). Lameness was detected and treated and lesions were recorded into a dairy record database (DairyCOMP 305; Valley Agricultural Software, Tulare, CA) by trained farm employees. All demographic, production, and foot lesion data were extracted from DairyCOMP 305 and merged with the sires' PTA information to form a unique database. Mixed logistic regression, general linear mixed, and multivariable Cox proportional hazards models were used to analyze the data. Sole ulcers, WLD, and DD incidence was significantly higher for cows affected with SU, WLD, or DD in previous lactations. Cows affected with WLD or DD during the first lactation had significantly higher WLD or DD incidence during the second and the third lactations. Cows affected with SU or WLD during their first lactation had significantly lower milk production during the second lactation and cows diagnosed with SU, WLD, or DD during their second lactation had higher second-lactation mature-equivalent 305-d milk yield. Sire PTA for milk and protein yield were significantly associated with the incidence of SU, WLD, and DD and incidence of SU and WLD, respectively. Sire PTA for several conformation traits were found to be associated with SU, WLD, and DD incidence. Cows that were affected with SU or WLD during their first lactation were at 1.18 or 1.43 higher hazard of culling than unaffected cows, respectively. In summary, we conclude that SU, WLD, and DD are highly repeatable across lactations and that high genetic merit for milk and protein production as well as milk production (phenotype) were significantly associated with higher risk of SU, WLD, and DD. Additionally, sire PTA for several conformation traits were significantly associated with their daughters' foot lesion incidence.

Genetic parameters for lameness and claw and leg diseases in dairy cows.

Lameness in dairy cows is a serious welfare and economic problem in dairy production. The majority of all lameness cases seem to stem from claw and leg diseases. Indirect selection on claw health potentially might be feasible with lameness as indicator trait. Therefore, the genetic parameters for the 2 traits were estimated by applying both linear and threshold models. In addition, the impact of environmental effects, parity, and stage of lactation was analyzed. In total, 8,299 locomotion scores (1-5) of 326 dairy cows and 708 claw and leg disease diagnoses or treatments of 335 dairy cows from the dairy research farm Karkendamm (Institute of Animal Breeding and Husbandry, Christian-Albrechts-University, Kiel, Germany) were analyzed. Lameness was defined by a locomotion score of ≥ 3. Days in milk were limited to the range of 10 to 350 d. To quantify the effect of the claw disease digital dermatitis, a second data set without this disease was built; 52.8 and 36.4% (without digital dermatitis) of the cows were treated at least once; 47.2% of the cows were clinically lame at least at one time. Genetic parameters were estimated bivariately using the average information restricted maximum likelihood procedure as implemented in the DMU software package. The heritability estimates derived from the threshold model were about twice as large as the values based on the linear model. For lameness, the threshold heritability increased from 0.15 to 0.22 and decreased for the diseases from 0.24 to 0.22 after exclusion of digital dermatitis. The genetic correlations were high and even increased from 0.60 to 0.72 after the exclusion of digital dermatitis, which suggests that lameness (locomotion score) seems to be a good indicator for claw and leg diseases. Digital dermatitis seems to affect the mobility of the dairy cow less strongly than other claw and leg diseases.

Estimation of the relative impact of treatment and herd management practices on prevention of digital dermatitis in French dairy herds.

The purpose of this study was to concurrently estimate the effect of different digital dermatitis (DD) treatment regimens and herd management practices on the occurrence of a new DD lesion. A controlled clinical trial was conducted and involved 4678 dairy cows from 52 French dairy farms where DD was endemic. Farms were allocated by minimisation to one of 4 treatment regimens, varying through the mode (footbath or collective spraying) and the frequency of application (2 days every 4 weeks or fortnightly). They were visited 7 times every 4 weeks by 14 trained investigators. Frailty Cox proportional hazards models were used to estimate the relative effect of potential risk factors and treatment practices on the time until the first occurrence of a DD lesion. At herd level, high initial DD prevalence strongly increased the risk for DD occurrence (HR=1.93, CI 1.23-3.04), as well as absence of hoof-trimming (HR=1.75, CI 1.36-2.27) and poor leg cleanliness (HR=2.44, CI 1.80-3.31). At animal level, Holstein breed (HR=1.92, CI 1.35-3.57) and high-productive cows (HR=1.26, CI 1.01-1.56) were identified to be at higher risk for DD compared to Normande breed and low-productive cows, respectively. Compared to individual topical antibiotic treatments alone, collective treatments tended to decrease the risk of DD occurrence only when applied over 2 days at least every fortnight (HR range=0.64-0.73).

Determining the heritable component of dairy cattle foot lesions.

Lameness and hoof health affect dairy cows as an animal welfare issue, in decreased milk production, and in premature culling. Selection schemes for dairy cattle focus on sire contribution to milk production, with little consideration of the cow's physical structure or disease probability. On 3 commercial California dairies, 6 phenotypic binary hoof traits that contribute to lameness were recorded: white line disease, sole ulcer, other claw horn lesions, foot rot (interdigital phlegmon), foot warts (digital dermatitis), and other lesions. Monthly lactation records were collected from December 2006 to April 2009 with weekly observations of hoof lesions for lame and dry cows. In addition to hoof lesion information, data on cows (n=5,043) included parentage, birth date, freshening date, lactation number, and date of lameness diagnosis. The prevalence of hoof lesions ranged from a low of 2.2% (foot rot) to a high of 17.1% (foot warts). The farm environment increased the odds ratio depending upon the lesion. Lameness was more common in early lactation and as lactation number increased. Using a threshold model, heritabilities and repeatabilities were estimated for each binary trait. The heritability for risk varied by lesion, with the higher estimates being 0.40 (95% confidence interval: 0.20-0.67) for digital dermatitis and 0.30 (95% confidence interval: 0.08-0.63) for sole ulcer. Including terms to account for cow productivity on either a 305-d mature-equivalent basis or a per-lactation basis had minimal effect on the heritability estimates, suggesting that selection for hoof health is not correlated with response to selection for greater milk production and that improvement could be made for both traits. The genetic component lends support for further genetic studies to identify loci contributing to some of the lesion phenotypes such as foot warts or sole ulcers, 2 of the top 3 causes of lameness in dairy cattle.

Relationships between bovine hoof disorders, body condition traits, and test-day yields.

A designed field study was conducted on 1,962 first-lactation Holstein cows kept on 7 large-scale dairy farms in Germany, in loose-housing systems on standard slatted flooring. Records of hoof disorders at trimming composed of subclinical as well as clinical cases were combined with body measurements and body condition scores, test-day records, and further individual cow data. The 6 most frequent disorders were laminitis, also known as sole hemorrhage (57.3% of all cows), dermatitis digitalis (17.0%), dermatitis interdigitalis (7.9%), white line disease (12.6%), sole ulcer (7.1%), and interdigital hyperplasia (5.5%). The most important environmental effects were herd-visit date and stage of lactation. Heifers between 50 and 99 d in milk had the highest frequencies for laminitis. Lighter cows were less susceptible to laminitis and white line disease, but had a higher prevalence of interdigital hyperplasia. Relationships between stature and white line disease as well as relationships between body condition score and dermatitis digitalis were nonlinear, resulting in an improved disorder status of cows with an intermediate condition score and average stature. Increased biomechanical stress caused by different factors (weight, social rank, standing time) is a presumed effect that leads to an increased susceptibility for hoof diseases. From a management perspective, under- and overconditioning should be avoided. Milk production traits differed between cows with and without laminitis-related claw horn lesions. Fat percentage and fat-to-protein ratio in the first month before trimming were significantly decreased for cows with a positive laminitis status. Hence, this finding points to metabolic disorders being associated with a higher risk for hoof diseases. Estimates of heritabilities for laminitis, dermatitis digitalis, dermatitis interdigitalis, white line disease, and sole ulcer were 0.09, 0.14, 0.10, 0.11, and 0.06 when applying a threshold model with a probit link function.