Genetic parameters of sole lesion recovery in Holstein cows.

Sole hemorrhage and sole ulcers, referred to as sole lesions, are important causes of lameness in dairy cattle. The objective of this study was to estimate the genetic parameters of a novel trait reflecting how well cows recovered from sole lesions and the genetic correlation of this trait with overall susceptibility to sole lesions. A cohort of Holstein dairy cows was prospectively enrolled on 4 farms and assessed at 4 timepoints: before calving, immediately after calving, in early lactation, and in late lactation. At each timepoint, sole lesions were recorded at the claw level by veterinary surgeons and used to define 2 binary traits: (1) susceptibility to sole lesions-whether animals were affected with sole lesions at least once during the study or were unaffected at every assessment, and (2) sole lesion recovery-whether sole lesions healed between early and late lactation. Animals were genotyped and pedigree details extracted from the national database. Analyses were conducted with BLUPF90 software in a single-step framework; genetic parameters were estimated from animal threshold models using Gibbs sampling. The genetic correlation between both traits was approximated as the correlation between genomic estimated breeding values, adjusting for their reliabilities. A total of 2,025 animals were used to estimate the genetic parameters of sole lesion susceptibility; 44% of animals recorded a sole lesion at least once during the study period. The heritability of sole lesion susceptibility, on the liability scale, was 0.25 (95% highest density interval = 0.16-0.34). A total of 498 animals were used to estimate the genetic parameters of sole lesion recovery; 71% of animals had recovered between the early and late lactation assessments. The heritability of sole lesion recovery, on the liability scale, was 0.27 (95% highest density interval = 0.02-0.52). The approximate genetic correlation between each trait was -0.11 (95% confidence interval = -0.20 to -0.02). Our results indicate that recovery from sole lesions is heritable. If this finding is corroborated in further studies, it may be possible to use selective breeding to reduce the frequency of chronically lame cows. As sole lesion recovery appears to be weakly genetically related to sole lesion susceptibility, successful genetic improvement of sole lesion recovery would benefit from selection on this trait directly.

Association between a genetic index for lameness resistance and the incidence of claw horn lesions in Holstein cows.

BACKGROUND: This study aimed to determine the association between the lameness advantage genetic index and four outcomes: sole haemorrhage (SH), sole ulcers (SU), white line lesions (WL), and lameness during mobility scoring. METHODS: We enrolled 2352 Holstein cows from four predominantly housed dairy herds in the UK. Cows were mobility scored and foot lesions recorded at four time points from before calving to late lactation. Cows were genotyped and genetic indexes were assigned to each cow following national genetic evaluations. Lameness records and genetic indexes were matched for 2107 cows. Four separate multivariable logistic regression models, which included farm and parity as covariables, were used to quantify the association between the lameness advantage index and whether animals were affected by SH, SU, WL, or lameness. RESULTS: The odds ratios (95% confidence intervals) for one-point increases in the lameness advantage index were 0.79 (0.72-0.86), 0.68 (0.59-0.78), 0.94 (0.84-1.04), and 0.82 (0.74-0.91) for SH, SU, WL, and lameness, respectively. The same trends were present when the sire's lameness advantage index was evaluated in place of the animal's own, although the strength of this association was generally weaker. CONCLUSION: The lameness advantage index is associated with SH, SU, and lameness, therefore selection on the lameness advantage index could be considered in herds aiming to reduce lameness. Where genomic testing of heifers is not conducted, sire lameness advantage index may still be effective to reduce SH and SU incidence.

Long-term, multidomain analyses to identify the breed and allelic effects in MSTN-edited pigs to overcome lameness and sustainably improve nutritional meat production.

Beef and mutton production has been aided by breeding to integrate allelic diversity for myostatin (MSTN), but a lack of diversity in the MSTN germplasm has limited similar advances in pig farming. Moreover, insurmountable challenges with congenital lameness and a dearth of data about the impacts of feed conversion, reproduction, and meat quality in MSTN-edited pigs have also currently blocked progress. Here, in a largest-to-date evaluation of multiple MSTN-edited pig populations, we demonstrated a practical alternative edit-site-based solution that overcomes the major production obstacle of hindlimb weakness. We also provide long-term and multidomain datasets for multiple breeds that illustrate how MSTN-editing can sustainably increase the yields of breed-specific lean meat and the levels of desirable lipids without deleteriously affecting feed-conversion rates or litter size. Apart from establishing a new benchmark for the data scale and quality of genome-edited animal production, our study specifically illustrates how gene-editing site selection profoundly impacts the phenotypic outcomes in diverse genetic backgrounds.

Transcriptome diversity and differential expression in supporting limb laminitis.

Laminitis results in impaired tissue integrity and Inflammation of the epidermal and dermal lamellae connecting the hoof capsule to the underlying distal phalanx and causes loss-of-use, poor quality of life and euthanasia in horses. Historically, studies to better understand the etiology of laminitis by documenting changes in gene expression were hampered by the paucity of gene annotation specific to hoof tissues. Next-generation sequencing enables improvements to annotation by incorporating equine- and hoof-specific transcripts. Here we characterize the hoof lamellar tissue transcriptome of naturally occurring supporting limb laminitis (SLL) using archived lamellar tissue from Thoroughbred racehorses consisting of 13 SLL hospital cases and seven age-matched control horses. This was achieved using: 1) Applied transcriptome annotation by long-read sequencing to document transcript diversity and 2) short-read RNA sequencing to document changes in gene expression correlating to the developmental and acute stages of naturally occurring SLL. 1.99Gbp of long-read transcriptome sequencing deeply documented 5067 unique loci, while short read RNA-seq under very stringent quality filters described 66 differentially expressed loci. Functional analysis of these loci revealed alterations in cell replication and growth, stress response and leukocyte recruitment and activation pathways. Differential expression of the Ezrin and TIMP3 genes suggests they may have utility as biomarkers for laminitis disease, while NR1D1 and genes relevant to the inflammasome are promising targets for novel pharmacological treatments.

Heritability and Genomic Architecture of Episodic Exercise-Induced Collapse in Border Collies.

An episodic nervous system disorder triggered by strenuous exercise, termed border collie collapse (BCC), exists in border collies and related breeds. The genetic basis of BCC is unknown but is believed to be a complex genetic disorder. Our goal was to estimate the heritability (h2SNP) of BCC, define its underlying genetic architecture, and identify associated genomic loci using dense whole-genome single-nucleotide polymorphism (SNP) genotyping data. Genotype data were obtained for ~440,000 SNPs from 343 border collies (168 BCC cases and 175 controls). h2SNP was calculated to be 49-61% depending on the estimated BCC prevalence. A total of 2407 SNPs across the genome accounted for nearly all the h2SNP of BCC, with an estimated 2003 SNPs of small effect, 349 SNPs of moderate effect, and 56 SNPs of large effect. Genome-wide association analyses identified significantly associated loci on chromosomes 1, 6, 11, 20, and 28, which accounted for ~5% of the total BCC h2SNP. We conclude that BCC is a moderately- to highly-heritable complex polygenetic disease resulting from contributions from hundreds to thousands of genetic variants with variable effect sizes. Understanding how much the BCC phenotype is determined by genetics and whether major gene mutations are likely to exist inform veterinarians and working/stock dog communities of the true nature of this condition.

Including milk production, conformation, and functional traits in multivariate models for genetic evaluation of lameness.

Lameness is a serious health and welfare issue that can negatively affect the economic performance of cows, especially on pasture-based dairy farms. However, most genetic predictions (GP) of lameness have low accuracy because lameness data are often incomplete as data are collected voluntarily by farmers in countries such as Australia. The objective of this study was to find routinely measured traits that are correlated with lameness and use them in multivariate evaluation models to improve the accuracy of GP for lameness. We used health events and treatments associated with lameness recorded by Australian farmers from 2002 to early 2019. The lameness incidence rates in Holstein and Jersey cows were 3.3% and 4.6%, respectively. We analyzed the records of 36 other traits (milk production, conformation, fertility, and survival traits) to estimate genetic correlations with lameness. The estimated heritability ± standard error (and repeatability ± standard error) for lameness in both Holstein and Jersey breeds were very low: 0.007 ± 0.002 (and 0.029 ± 0.002) and 0.005 ± 0.003 (and 0.027 ± 0.006), respectively, in univariate sire models. For the GP models, we tested including measurements of overall type to prediction models for Holsteins, stature and body length for Jersey, and milk yield and fertility traits for both breeds. The average accuracy of GP, calculated from prediction error variances, were 0.38 and 0.24 for Holstein and Jersey sires, respectively, when estimated using univariate sire models and both increased to 0.43 using multivariate sire models. In conclusion, we found that the accuracy of GP for lameness could be improved by including genetically correlated traits in a multivariate model. However, to further improve the accuracy of predictions of lameness, precise identification and recording incidences of hoof or leg disorder, or large-scale recording of locomotion and claw scores by trained personnel should be considered.

Aged Tmem106b knockout mice display gait deficits in coincidence with Purkinje cell loss and only limited signs of non-motor dysfunction.

Genetic variants in TMEM106B are a major risk factor for several neurodegenerative diseases including frontotemporal degeneration, limbic-predominant age-related TDP-43 encephalopathy, Parkinson's disease, late-onset-Alzheimer's disease and constitute a genetic determinant of differential aging. TMEM106B encodes an integral lysosomal membrane protein but its precise physiological function in the central nervous system remains enigmatic. Presently, we aimed to increase understanding of TMEM106B contribution to general brain function and aging. We analyzed an aged cohort of Tmem106b knockout-, heterozygote and wild-type mice in a behavioral test battery including assessments of motor function as well as, social, emotional and cognitive function. Aged Tmem106b knockout (KO) mice displayed diverse behavioral deficits including motor impairment, gait defects and reduced startle reactivity. In contrast, no prominent deficits were observed in social, emotional or cognitive behaviors. Histologically, we observed late-onset loss of Purkinje cells followed by reactive gliosis in the cerebellum, which likely contributed to progressive decline in motor function and gait defects in particular. Reactive gliosis was not restricted to the cerebellum but observed in different areas of the brain including the brain stem and parts of the cerebral cortex. Surviving Purkinje cells showed vacuolated lysosomes in the axon initial segment, implicating TMEM106B-dependent lysosomal trafficking defects as the underlying cause of axonal and more general neuronal dysfunction contributing to behavioral impairments. Our experiments help to elucidate how TMEM106B affects spatial neuronal homeostasis and exemplifies a critical role of TMEM106B in neuronal cells for survival.

Interleukin-17A pathway target genes are upregulated in Equus caballus supporting limb laminitis.

Supporting Limb Laminitis (SLL) is a painful and crippling secondary complication of orthopedic injuries and infections in horses, often resulting in euthanasia. SLL causes structural alterations and inflammation of the interdigitating layers of specialized epidermal and dermal tissues, the lamellae, which suspend the equine distal phalanx from the hoof capsule. Activation of the interleukin-17A (IL-17A)-dependent inflammatory pathway is an epidermal stress response that contributes to physiologic cutaneous wound healing as well as pathological skin conditions. As a first test of the hypothesis that hoof lamellae of horses diagnosed with SLL also respond to stress by activating the IL-17A pathway, the expression of IL-17A, IL-17 receptor subunit A and 11 IL-17A effector genes was measured by RT-PCR or qPCR. Lamellar tissue was isolated from Thoroughbreds euthanized due to naturally occurring SLL and in age and breed matched non-laminitic controls. By RT-PCR, the IL-17 Receptor A subunit was expressed in both non-laminitic and laminitic tissues, while IL-17A was primarily detectable in laminitic tissues. IL-17A target gene expression was undetectable in non-laminitic samples with the exception of weak detection of DEFB4B, S100A9 and PTSG2. In contrast, all target genes examined, except CCL20, were expressed by some or all laminitic samples. By qPCR, severe acute (n = 7) SLL expressed ~15-100 fold higher levels of DEFB4B and S100A9 genes compared to non-laminitic controls (n = 8). DEFB4B was also upregulated in developmental/subclinical (n = 8) and moderate acute (n = 7) by ~ 5-fold, and in severe chronic (n = 5) by ~15-200 fold. In situ hybridization (DEFB4) and immunofluorescence (calprotectin, a dimer of S100A9/S100A8 proteins) demonstrated expression in keratinocytes, primarily in suprabasal cell layers, from SLL samples. These data demonstrate upregulation of a cohort of IL-17A target genes in SLL and support the hypothesis that similarities in the response to stresses and damage exist between equine and human epidermal tissues.

Structural and functional features of medium spiny neurons in the BACHDΔN17 mouse model of Huntington's Disease.

In the BACHD mouse model of Huntington's disease (HD), deletion of the N17 domain of the Huntingtin gene (BACHDΔN17, Q97) has been reported to lead to nuclear accumulation of mHTT and exacerbation of motor deficits, neuroinflammation and striatal atrophy (Gu et al., 2015). Here we characterized the effect of N17 deletion on dorsolateral striatal medium spiny neurons (MSNs) in BACHDΔN17 (Q97) and BACWTΔN17 (Q31) mice by comparing them to MSNs in wildtype (WT) mice. Mice were characterized on a series of motor tasks and subsequently whole cell patch clamp recordings with simultaneous biocytin filling of MSNs in in vitro striatal slices from these mice were used to comprehensively assess their physiological and morphological features. Key findings include that: Q97 mice exhibit impaired gait and righting reflexes but normal tail suspension reflexes and normal coats while Q31 mice do not differ from WT; intrinsic membrane and action potential properties are altered -but differentially so- in MSNs from Q97 and from Q31 mice; excitatory and inhibitory synaptic currents exhibit higher amplitudes in Q31 but not Q97 MSNs, while excitatory synaptic currents occur at lower frequency in Q97 than in WT and Q31 MSNs; there is a reduced total dendritic length in Q31 -but not Q97- MSNs compared to WT, while spine density and number did not differ in MSNs in the three groups. The findings that Q31 MSNs differed from Q97 and WT neurons with regard to some physiological features and structurally suggest a novel role of the N17 domain in the function of WT Htt. The motor phenotype seen in Q97 mice was less robust than that reported in an earlier study (Gu et al., 2015), and the alterations to MSN physiological properties were largely consistent with changes reported previously in a number of other mouse models of HD. Together this study indicates that N17 plays a role in the modulation of the properties of MSNs in both mHtt and WT-Htt mice, but does not markedly exacerbate HD-like pathogenesis in the BACHD model.

Proteomic profiling of proteins in the dorsal horn of the spinal cord in dairy cows with chronic lameness.

Chronic lameness affects bovine welfare and has a negative economic impact in dairy industry. Moreover, due to the translational gap between traditional pain models and new drugs development for treating chronic pain states, naturally occurring painful diseases could be a potential translational tool for chronic pain research. We therefore employed liquid chromatography tandem mass spectrometry (LC-MS/MS) to stablish the proteomic profile of the spinal cord samples from lumbar segments (L2-L4) of chronic lame dairy cows. Data were validated and quantified through software tool (Scaffold® v 4.0) using output data from two search engines (SEQUEST® and X-Tandem®). Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analysis was performed to detect proteins interactions. LC-MS/MS identified a total amount of 177 proteins; of which 129 proteins were able to be quantified. Lame cows showed a strong upregulation of interacting proteins with chaperone and stress functions such as Hsp70 (p < 0.006), Hsc70 (p < 0.0079), Hsp90 (p < 0.015), STIP (p > 0.0018) and Grp78 (p <0.0068), and interacting proteins associated to glycolytic pathway such as; γ-enolase (p < 0.0095), α-enolase (p < 0.013) and hexokinase-1 (p < 0.028). It was not possible to establish a clear network of interaction in several upregulated proteins in lame cows. Non-interacting proteins were mainly associated to redox process and cytoskeletal organization. The most relevant down regulated protein in lame cows was myelin basic protein (MBP) (p < 0.02). Chronic inflammatory lameness in cows is associated to increased expression of stress proteins with chaperone, metabolism, redox and structural functions. A state of endoplasmic reticulum stress and unfolded protein response (UPR) might explain the changes in protein expression in lame cows; however, further studies need to be performed in order to confirm these findings.

Distribution analysis of single nucleotide polymorphisms related to feet and legs and their association with lameness in Vrindavani cattle.

Lameness is one of the most serious economic problems in dairy animals. The present study was undertaken to identify the SNPs associated with lameness in Vrindavani, a synthetic crossbred cattle developed in India. A total of 187 cows were screened for lameness at Cattle and Buffalo Farm, Indian Veterinary Research Institute, Izatnagar, India and 16.04% prevalence was noticed. The effect of age, body weight, parity, and peak yield was not significant on lameness score. Heritability estimate of lameness score was low (0.07 ± 0.01). A total of 90 Vrindavani cows were genotyped by PCR-RFLP for 10 SNPs that were reported to have association with feet and legs in cattle. Five SNPs displayed significant departure from Hardy Weinberg equilibrium. Varying levels of heterozygosity, polymorphic information content, and allelic diversity were noticed at different SNPs. Odds ratio and least squares analysis revealed a significant association (P < 0.05) of three SNPs with lameness in the herd. Cows with AG, TT, and GG genotypes respectively at rs41632254, rs41603160, and rs41636945 loci were less prone to lameness. These genetic markers would certainly aid in development of an early detection system for lameness.

New insights into the association between lameness, behavior, and performance in Simmental cows.

In a herd of 100 milking Simmental cows, data of performance and behavior parameters were collected automatically with different systems such as pedometers, an automatic milking system, and automatic weighing troughs for 1 yr. Performance measures were several milking-related parameters, live weight, as well as feed intake. Behavior-associated measures were feeding behavior (e.g. feeding duration, number of visits to the trough, and feeding pace) as well as activity such as lying duration, number of lying bouts, and overall activity. In the same time, lameness status of every cow was assessed with weekly locomotion scoring. According to the score animals were then classified lame (score 4 or 5) or nonlame (score 1, 2, or 3). From these data in total, 25 parameters summarized to daily values were evaluated for their ability to determine the lameness status of a cow. Data were analyzed with a regularized regression method called elastic net with the outcome lame or nonlame. The final model had a high prediction accuracy with an area under the curve of 0.91 [95% confidence interval (CI) = 0.88-0.94]. Specificity was 0.81 (95% CI = 0.73-0.85) and sensitivity was 0.94 (95% CI = 0.88-1.00). The most important factors associated with a cow being lame were number of meals, average feed intake per meal, and average duration of a meal. Lame cows fed in fewer and shorter meals with a decreased intake per meal. Milk yield and lying-behavior-associated parameters were relevant in the model, too, but only as parts of interaction terms demonstrating their strong dependence on other factors. A higher milk yield only resulted in higher risk of being lame if feed intake was decreased. The same accounts for lying duration: only if lying time was below the 50% quantile did an increased milk yield result in a higher risk of being lame. The association of lameness and daily lying duration was influenced by daily feeding duration and feeding duration at daytime. The results of the study give deeper insights on how the association between behavior and performance parameters and lameness is influenced by intrinsic factors in particular and that many of these have to be considered when trying to predict lameness based on such data. The findings lead to a better understanding why, for instance, lying duration or milk yield seem to be highly correlated with lameness in cows but still have not been overly useful as parameters in other lameness detection models.

Short communication: Use of lameness scoring to genetically improve claw health in Austrian Fleckvieh, Brown Swiss, and Holstein cattle.

The specific objective of this study was to evaluate the use of lameness scoring to genetically improve claw health in Austrian Fleckvieh, Brown Swiss, and Holstein cows based on data from the "Efficient Cow" project. In 2014, a 1-yr data collection was carried out. Data from 6,519 cows kept on 161 farms were recorded. At each time of milk recording, lameness scores were assessed by trained staff of the milk recording organizations. Hoof trimming on these farms was documented and recorded as well. Veterinarian diagnoses and culling due to foot and leg problems from these farms were available from the routine recording system. As repeated lameness records per cow and lactation were available, an overall lactation lameness score was calculated. Estimated heritabilities for lameness were 0.11, 0.05, and 0.09 for Fleckvieh, Brown Swiss, and Holstein, respectively; however, only heritability estimates for Fleckvieh were significantly different from zero. Breeding values for lameness were obtained, reversed in sign, and cows were ranked according to their breeding value. A low breeding value for lameness resistance (the bottom 10% of the cows) was associated with a significantly higher frequency of trimmed cows, which indicates that the cows selected by the farmer to be trimmed are not completely random. Additionally, a high breeding value for lameness resistance (the top 10% of the cows) was associated with lower frequencies of claw diseases recorded at trimming, claw and leg diagnoses, and culling due to foot and leg problems, which highlights the usefulness of lameness scoring for genetic improvement of claw health. Overall, selecting for a better lameness score has the potential to reduce claw diseases, especially the frequency of severe claw diseases that lead to culling.

Genetic selection for hoof health traits and cow mobility scores can accelerate the rate of genetic gain in producer-scored lameness in dairy cows.

Cattle breeding programs that strive to reduce the animal-level incidence of lameness are often hindered by the availability of informative phenotypes. As a result, indicator traits of lameness (i.e., hoof health and morphological conformation scores) can be used to improve the accuracy of selection and subsequent genetic gain. Therefore, the objectives of the present study were to estimate the variance components for hoof health traits using various phenotypes collected from a representative sample of Irish dairy cows. Also of interest to the present study was the genetic relationship between both hoof health traits and conformation traits with producer-scored lameness. Producer-recorded lameness events and linear conformation scores from 307,657 and 117,859 Irish dairy cows, respectively, were used. Data on hoof health (i.e., overgrown sole, white line disease, and sole hemorrhage), mobility scores, and body condition scores were also available from a research study on up to 11,282 Irish commercial dairy cows. Linear mixed models were used to quantify variance components for each trait and to estimate genetic correlations among traits. The estimated genetic parameters for hoof health traits in the present study were greater (i.e., heritability range: 0.005 to 0.27) than previously reported in dairy cows. With the exception of analyses that considered hoof health traits in repeatability models, little difference in estimated variance components existed among the various hoof-health phenotypes. Results also suggest that producer-recorded lameness is correlated with both hoof health (i.e., genetic correlation up to 0.48) and cow mobility (i.e., genetic correlation = 0.64). Moreover, cows that genetically tend to have rear feet that appear more parallel when viewed from the rear are also genetically more predisposed to lameness (genetic correlation = 0.39); genetic correlations between lameness and other feet and leg type traits, as well as between lameness and frame type traits, were not different from zero. Results suggest that if the population breeding goal was to reduce lameness incidence, improve hoof health, or improve cow mobility, genetic selection for either of these traits should indirectly benefit the other traits. Results were used to quantify the genetic gains achievable for lameness when alternative phenotypes are available.

Cow- and herd-level factors associated with lameness in small-scale grazing dairy herds in Brazil.

This cross-sectional study aimed to assess lameness occurrence and to identify the associated risk factors in small-scale grazing dairy herds. Forty four farms (mean lactating herd size was 42 cows, SD = 11.2, range: 28-74) located in the south of Brazil were visited twice, approximately 4 months apart, in 2015. Locomotion was scored in 1633 and 1836 cows at the first and second visit, respectively. Potential risk factors for lameness were assessed through inspection of cows and facilities, and a questionnaire for farmers about herd management practices. Multilevel logistic regressions, using herd as random effect, were fitted to investigate the cow-level risk factors for accumulated incident (not lame at the first visit but lame on the second), chronic (lame on both visits) and recovered (lame at the first visit but sound on the second) cases of lameness. A multilevel linear regression, using municipality as a random effect, was fitted for herd-level analysis. Cumulative lameness incidence between two visits (1110 cows in 41 herds) was 29.6% (range: 0-80); lameness prevalence (n = 44 herds) was 31% (10-70) and 35% (5-76) at the first and second visits, respectively. The odds of incident cases were greater in Holstein cows [odds ratio (OR) = 4.0, 95% confidence interval 2.1-7.6] compared with Jerseys, in cows in parities 2-3 (OR 2.5, 1.4-4.4) or >3 (OR 6.6, 3.3-13.1) relative to parity 1, in cows having a low body condition score (BCS) of 2-2.75 or 3 on the first visit (OR 2, 1.1-3.7), and in cows with observed hoof abnormalities (OR 2.5, 1.3-4.7). Similar associations were found for chronic cases, with Holstein and crossbred cows having greater odds of lameness, compared to Jersey, and chronic cases being more likely in cows with increasing parity, with BCS at first visit of 2-2.75, and with presence of hoof abnormalities. Jersey or crossbred cows (OR 3.2, 1.3-8.1) and cows in parity 1-2 (OR 3.6, 1.6-8.4) had higher probability of recovery from lameness. Having a herd composed of Holstein cows was associated with 13.5% (CI 4.3-22.8) greater incidence of lameness (n = 35). For every 1 km/h increase in the average speed of movement of the herd to or from milking, lameness incidence increased by 5% (CI 0.1-10). Given that the occurrence of lameness was high there is great opportunity to reduce lameness in this population. This study highlights some management and prevention practices that may reduce lameness in these grazing herds.

Genetic analysis of efficiency traits in Austrian dairy cattle and their relationships with body condition score and lameness.

This study is part of a larger project whose overall objective was to evaluate the possibilities for genetic improvement of efficiency in Austrian dairy cattle. In 2014, a 1-yr data collection was carried out. Data from 6,519 cows kept on 161 farms were recorded. In addition to routinely recorded data (e.g., milk yield, fertility, disease data), data of novel traits [e.g., body weight (BW), body condition score (BCS), lameness score, body measurements] and individual feeding information and feed quality were recorded on each test-day. The specific objective of this study was to estimate genetic parameters for efficiency (related) traits and to investigate their relationships with BCS and lameness in Austrian Fleckvieh, Brown Swiss, and Holstein cows. The following efficiency (related) traits were considered: energy-corrected milk (ECM), BW, dry matter intake (DMI), energy intake (INEL), ratio of milk output to metabolic BW (ECM/BW0.75), ratio of milk output to DMI (ECM/DMI), and ratio of milk energy output to total energy intake (LE/INEL, LE = energy in milk). For Fleckvieh, the heritability estimates of the efficiency (related) traits ranged from 0.11 for LE/INEL to 0.44 for BW. Heritabilities for BCS and lameness were 0.19 and 0.07, respectively. Repeatabilities were high and ranged from 0.30 for LE/INEL to 0.83 for BW. Heritability estimates were generally lower for Brown Swiss and Holstein, but repeatabilities were in the same range as for Fleckvieh. In all 3 breeds, more-efficient cows were found to have a higher milk yield, lower BW, slightly higher DMI, and lower BCS. Higher efficiency was associated with slightly fewer lameness problems, most likely due to the lower BW (especially in Fleckvieh) and higher DMI of the more-efficient cows. Body weight and BCS were positively correlated. Therefore, when selecting for a lower BW, BCS is required as additional information because, otherwise, no distinction between large animals with low BCS and smaller animals with normal BCS would be possible.

Murine Sialidase Neu3 facilitates GM2 degradation and bypass in mouse model of Tay-Sachs disease.

Tay-Sachs disease is a severe lysosomal storage disorder caused by mutations in Hexa, the gene that encodes for the α subunit of lysosomal ß-hexosaminidase A (HEXA), which converts GM2 to GM3 ganglioside. Unexpectedly, Hexa-/- mice have a normal lifespan and show no obvious neurological impairment until at least one year of age. These mice catabolize stored GM2 ganglioside using sialidase(s) to remove sialic acid and form the glycolipid GA2, which is further processed by ß-hexosaminidase B. Therefore, the presence of the sialidase (s) allows the consequences of the Hexa defect to be bypassed. To determine if the sialidase NEU3 contributes to GM2 ganglioside degradation, we generated a mouse model with combined deficiencies of HEXA and NEU3. The Hexa-/-Neu3-/- mice were healthy at birth, but died at 1.5 to 4.5months of age. Thin-layer chromatography and mass spectrometric analysis of the brains of Hexa-/-Neu3-/- mice revealed the abnormal accumulation of GM2 ganglioside. Histological and immunohistochemical analysis demonstrated cytoplasmic vacuolation in the neurons. Electron microscopic examination of the brain, kidneys and testes revealed pleomorphic inclusions of many small vesicles and complex lamellar structures. The Hexa-/-Neu3-/- mice exhibited progressive neurodegeneration with neuronal loss, Purkinje cell depletion, and astrogliosis. Slow movement, ataxia, and tremors were the prominent neurological abnormalities observed in these mice. Furthermore, radiographs revealed abnormalities in the skeletal bones of the Hexa-/-Neu3-/- mice. Thus, the Hexa-/-Neu3-/- mice mimic the neuropathological and clinical abnormalities of the classical early-onset Tay-Sachs patients, and provide a suitable model for the future pre-clinical testing of potential treatments for this condition.

Mice deficient in NRROS show abnormal microglial development and neurological disorders.

Microglia and other tissue-resident macrophages within the central nervous system (CNS) have essential roles in neural development, inflammation and homeostasis. However, the molecular pathways underlying their development and function remain poorly understood. Here we report that mice deficient in NRROS, a myeloid-expressed transmembrane protein in the endoplasmic reticulum, develop spontaneous neurological disorders. NRROS-deficient (Nrros-/-) mice show defects in motor functions and die before 6 months of age. Nrros-/- mice display astrogliosis and lack normal CD11bhiCD45lo microglia, but they show no detectable demyelination or neuronal loss. Instead, perivascular macrophage-like myeloid cells populate the Nrros-/- CNS. Cx3cr1-driven deletion of Nrros shows its crucial role in microglial establishment during early embryonic stages. NRROS is required for normal expression of Sall1 and other microglial genes that are important for microglial development and function. Our study reveals a NRROS-mediated pathway that controls CNS-resident macrophage development and affects neurological function.

Genetic parameters for lameness, mastitis and dagginess in a multi-breed sheep population.

The objective of the present study was to quantify the extent of genetic variation in three health-related traits namely dagginess, lameness and mastitis, in an Irish sheep population. Each of the health traits investigated pose substantial welfare implications as well as considerable economic costs to producers. Data were also available on four body-related traits, namely body condition score (BCS), live weight, muscle depth and fat depth. Animals were categorised as lambs (<365 days old) or ewes (⩾365 days old) and were analysed both separately and combined. After edits, 39 315 records from 264 flocks between the years 2009 and 2015 inclusive were analysed. Variance components were estimated using animal linear mixed models. Fixed effects included contemporary group, represented as a three-way interaction between flock, date of inspection and animal type (i.e. lamb, yearling ewe (i.e. females ⩾365 days but <730 days old that have not yet had a recorded lambing) or ewe), animal breed proportion, coefficients of heterosis and recombination, animal gender (lambs only), animal parity (ewes only; lambs were assigned a separate 'parity') and the difference in age of the animal from the median of the respective parity/age group. An additive genetic effect and residual effect were both fitted as random terms with maternal genetic and non-genetic components also considered for traits of the lambs. The direct heritability of dagginess was similar across age groups (0.14 to 0.15), whereas the direct heritability of lameness ranged from 0.06 (ewes) to 0.12 (lambs). The direct heritability of mastitis was 0.04. For dagginess, 13% of the phenotypic variation was explained by dam litter, whereas the maternal heritability of dagginess was 0.05. The genetic correlation between ewe and lamb dagginess was 0.38; the correlation between ewe and lamb lameness was close to zero but was associated with a large standard error. Direct genetic correlations were evident between dagginess and BCS in ewes and between lameness and BCS in lambs. The present study has demonstrated that ample genetic variation exists for all three health traits investigated indicating that genetic improvement is indeed possible.

Genetic relationship between leg problems and bone quality traits in a random mating broiler population.

We herein report the genetic association between leg problems and bone quality traits in a random mating broiler control population. The leg problem traits were valgus (VL), varus (VR), and tibial dyschondroplasia (TD), and that of bone quality were shank weight (SW), shank length (SL), shank diameter (SDIAM), tibia weight (TW), tibia length (TL), tibia diameter (TDIAM), tibia density (TDEN), tibia breaking strength (TBS), tibia mineral density (TMD), tibia mineral content (TMC), and tibia ash content (TAC). A threshold-linear mixed model, implemented via a Bayesian approach, was employed for the joint analysis of the traits. Genetic correlations of leg problems with bone quality traits ranged from -0.06 to 0.11 suggesting that genetic relationship between leg problems and quality is weak, and management strategies could better alleviate leg problems than genetic improvement.