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Blood biomarkers may be used to detect physiological imbalance and potential disease. However, blood sampling is difficult and expensive, and not applicable in commercial settings. Instead, individual milk samples are readily available at low cost, can be sampled easily and analysed instantly. The present observational study sampled blood and milk from 234 Holstein dairy cows from experimental herds in six European countries. The objective was to compare the use of three different sets of milk biomarkers for identification of cows in physiological imbalance and thus at risk of developing metabolic or infectious diseases. Random forests was used to predict body energy balance (EBAL), index for physiological imbalance (PI-index) and three clusters differentiating the metabolic status of cows created on basis of concentrations of plasma glucose, β-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA) and serum IGF-1. These three metabolic clusters were interpreted as cows in balance, physiological imbalance and "intermediate cows" with physiological status in between. The three sets of milk biomarkers used for prediction were: milk Fourier transform mid-IR (FT-MIR) spectra, 19 immunoglobulin G (IgG) N-glycans and 8 milk metabolites and enzymes (MME). Blood biomarkers were sampled twice; around 14 days after calving (days in milk (DIM)) and around 35 DIM. MME and FT-MIR were sampled twice weekly 1-50 DIM whereas IgG N-glycan were measured only four times. Performances of EBAL and PI-index predictions were measured by coefficient of determination (R 2 cv ) and root mean squared error (RMSE cv ) from leave-one-cow-out cross-validation (cv). For metabolic clusters, performance was measured by sensitivity, specificity and global accuracy from this cross-validation. Best prediction of PI-index was obtained by MME (R 2 cv  = 0.40 (95 % CI: 0.29-0.50) at 14 DIM and 0.35 (0.23-0.44) at 35 DIM) while FT-MIR showed a better performance than MME for prediction of EBAL (R 2 cv  = 0.28 (0.24-0.33) vs 0.21 (0.18-0.25)). Global accuracies of predicting metabolic clusters from MME and FT-MIR were at the same level ranging from 0.54 (95 % CI: 0.39-0.68) to 0.65 (0.55-0.75) for MME and 0.51 (0.37-0.65) to 0.68 (0.53-0.81) for FT-MIR. R 2 cv and accuracies were lower for IgG N-glycans. In conclusion, neither EBAL nor PI-index were sufficiently well predicted to be used as a management tool for identification of risk cows. MME and FT-MIR may be used to predict the physiological status of the cows, while the use of IgG N-glycans for prediction still needs development. Nevertheless, accuracies need to be improved and a larger training data set is warranted., Competing Interests: Declaration of Competing Interest There is no direct financial interest of the authors and affiliations in the subject matter discussed in the manuscript. All financial support is identified in the Funding section., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bovine P-selectin (SELP) mediates leukocyte rolling and primes leukocyte adhesion to endothelium, both essential for leukocyte recruitment to an infection site. We investigated SELP-mediated adhesion between bovine peripheral blood leukocytes (PBLs) and cultured bovine aortic endothelial cells pre-activated with lipopolysaccharide (LPS). We examined gene polymorphism for bovine selectins SELP, l-selectin (SELL) and E-selectin (SELE) and compared their SNP frequency between five dairy breeds (Holstein, Friesian, Jersey, Ayrshire and Brown Swiss). LPS treatment caused a rapid (10min) and slower (4h) enhancement of PBL adhesion (P<0.01). Antibody blocking of SELP inhibited LPS induced cell adhesion. SELP was highly polymorphic, with 9 of the 13 SNPs in its exons, whereas only three synonymous SNPs in SELL and one in SELE. The resulting amino acid changes for the three missense SELP SNP were located in the lectin domain and in two consensus repeat (CR) regions, CR2 and CR5. The Val475Met variant locus in the CR4 and CR5 linking region was very close to a predicted N-acetyl-d-glucosamine glycosylation site, which is likely to influence SELP function. The AA genotype was under-represented, only being found in 1% of 373 heifers genotyped from the 5 breeds (P=0.056), suggesting that AA homozygous animals carrying the Val475Met substitution for SELP may have compromised development. Our study thus confirmed that SELP mediates the attachment of PBL to endothelium and provides novel evidence that its high polymorphism is likely to affect biological function. This may potentially influence leukocyte migration and fertility, both key to successful performance in dairy cows., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

New Mendelian genetic conditions, which adversely affect livestock, arise all the time. To manage them effectively, some methods need to be devised that are quick and accurate. Until recently, finding the causal genomic site of a new autosomal recessive genetic disease has required a two-stage approach using single-nucleotide polymorphism (SNP) chip genotyping to locate the region containing the new variant. This region is then explored using fine-mapping methods to locate the actual site of the new variant. This study explores bioinformatic methods that can be used to identify the causative variants of recessive genetic disorders with full penetrance with just nine whole genome-sequenced animals to simplify and expedite the process to a one-step procedure. Using whole genome sequencing of only three cases and six carriers, the site of a novel variant causing perinatal mortality in Irish moiled calves was located. Four methods were used to interrogate the variant call format (VCF) data file of these nine animals, they are genotype criteria (GCR), autozygosity-by-difference (ABD), variant prediction scoring, and registered SNP information. From more than nine million variants in the VCF file, only one site was identified by all four methods (Chr4: g.77173487A>T (ARS-UCD1.2 (GCF_002263795.1)). This site was a splice acceptor variant located in the glucokinase gene (GCK). It was verified on an independent sample of animals from the breed using genotyping by polymerase chain reaction at the candidate site and autozygosity-by-difference using SNP-chips. Both methods confirmed the candidate site. Investigation of the GCR method found that sites meeting the GCR were not evenly spread across the genome but concentrated in regions of long runs of homozygosity. Locating GCR sites was best performed using two carriers to every case, and the carriers should be distantly related to the cases, within the breed concerned. Fewer than 20 animals need to be sequenced when using the GCR and ABD methods together. The genomic site of novel autosomal recessive Mendelian genetic diseases can be located using fewer than 20 animals combined with two bioinformatic methods, autozygosity-by-difference, and genotype criteria. In many instances it may also be confirmed with variant prediction scoring. This should speed-up and simplify the management of new genetic diseases to a single-step process. [ABSTRACT FROM AUTHOR]

Bovine Tuberculosis (bTB) caused by Mycobacterium bovis is a livestock disease of global economic and public health importance. There are currently no effective vaccines available for livestock and so control relies on animal level surveillance and pasteurization of dairy products. A new alternative control approach is to exploit the genetic variability of the host; recent studies have demonstrated that breeding European taurine cattle, such as Holsteins for increased resistance to bTB is feasible. The utility of such an approach is still unknown for African cattle populations. This study aims to assess genetic variation in bTB resistance and the underlying genomic architecture of cattle in Cameroon. We conducted a cross-sectional study of 2,346 slaughter cattle in Cameroon. Retropharyngeal lymph node samples were collected and cultured on Lowenstein Jensen media and the BACTEC MGIT 960 system, and M. bovis was identified using the Hain® Genotype kits. A total of 153 cattle were positive for M. bovis and were archived along with a random selection of negative samples. In this study, we genotyped archived samples from 212 cattle. Their genomic diversity was characterized using PCA, hierarchical clustering and admixture analysis. We assessed genetic variation in bTB resistance using heritability analysis and compared quantitative trait loci. Previous research on this study population have shown that Fulani cattle are more susceptible to bTB than mixed breeds. However, here we show that these apparent phenotypic differences in breeds are not reflected by clear genomic differences. At the genetic level, both the Fulani and mixed cattle show similar patterns of admixture with evidence of both taurine and indicine ancestry. There was little European taurine introgression within the studied population. Hierarchical clustering showed clusters of cattle that differed in their susceptibility to bTB. Our findings allude to bTB resistance being polygenic in nature. This study highlights the potential for genetic control of bTB in Africa and the need for further research into the genetics of bTB resistance within African cattle populations. [ABSTRACT FROM AUTHOR]