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Background: Since their domestication 10,500 years ago, goat populations with distinctive genetic backgrounds have adapted to a broad variety of environments and breeding conditions. The VarGoats project is an international 1000-genome resequencing program designed to understand the consequences of domestication and breeding on the genetic diversity of domestic goats and to elucidate how speciation and hybridization have modeled the genomes of a set of species representative of the genus Capra. Findings: A dataset comprising 652 sequenced goats and 507 public goat sequences, including 35 animals representing eight wild species, has been collected worldwide. We identified 74,274,427 single nucleotide polymorphisms (SNPs) and 13,607,850 insertion-deletions (InDels) by aligning these sequences to the latest version of the goat reference genome (ARS1). A Neighbor-joining tree based on Reynolds genetic distances showed that goats from Africa, Asia and Europe tend to group into independent clusters. Because goat breeds from Oceania and Caribbean (Creole) all derive from imported animals, they are distributed along the tree according to their ancestral geographic origin. Conclusions: We report on an unprecedented international effort to characterize the genome-wide diversity of domestic goats. This large range of sequenced individuals represents a unique opportunity to ascertain how the demographic and selection processes associated with post-domestication history have shaped the diversity of this species. Data generated for the project will also be extremely useful to identify deleterious mutations and polymorphisms with causal effects on complex traits, and thus will contribute to new knowledge that could be used in genomic prediction and genome-wide association studies. [ABSTRACT FROM AUTHOR]

Background: Goats were domesticated 10,500 years ago to supply humans with useful resources. Since then, specialized breeds that are adapted to their local environment have been developed and display specific genetic profiles. The VarGoats project is a 1000 genomes resequencing program designed to cover the genetic diversity of the Capra genus. In this study, our main objective was to assess the use of sequence data to detect genomic regions associated with traits of interest in French Alpine and Saanen breeds. Results: Direct imputation from the GoatSNP50 BeadChip genotypes to sequence level was investigated in these breeds using FImpute and different reference panels: within-breed, all Capra hircus sequenced individuals, European goats and French mainland goats. The best results were obtained with the French goat panel with allele and genotype concordance rates reaching 0.86 and 0.75 in the Alpine and 0.86 and 0.73 in the Saanen breed respectively. Mean correlations tended to be low in both breeds due to the high proportion of variants with low frequencies. For association analysis, imputation was performed using FImpute for 1129 French Alpine and Saanen males using within-breed and French panels on 23,338,436 filtered variants. The association results of both imputation scenarios were then compared. In Saanen goats, a large region on chromosome 19 was significantly linked to semen volume and milk yield in both scenarios. Significant variants for milk yield were annotated for 91 genes on chromosome 19 in Saanen goats. For semen volume, the annotated genes include YBOX2 which is related to azoospermia or oligospermia in other species. New signals for milk yield were detected on chromosome 2 in Alpine goats and on chromosome 5 in Saanen goats when using a multi-breed panel. Conclusion: Even with very small reference populations, an acceptable imputation quality can be achieved in French dairy goats. GWAS on imputed sequences confirmed the existence of QTLs and identified new regions of interest in dairy goats. Adding identified candidates to a genotyping array and sequencing more individuals might corroborate the involvement of identified regions while removing potential imputation errors. [ABSTRACT FROM AUTHOR]

Background: S. aureus is one of the main pathogens responsible for the intra-mammary infection in dairy ruminants. Although much work has been carried out to understand the complex physiological and cellular events that occur in the mammary gland in response to S. aureus, the protective mechanisms are still poorly understood. The objectives of the present study were to investigate gene expression during the early response of the goat mammary gland to an experimental challenge with S. aureus, in order to better understand the local and systemic response and to compare them in two divergent lines of goat selected for high and low milk somatic cell scores. Results: No differences in gene expression were found between high and low SCS (Somatic Cells Score) selection lines. Analysing the two groups together, an expression of 300 genes were found to change from T0 before infection, and T4 at 24 hours and T5 at 30 hours following challenge. In blood derived white blood cells 8 genes showed increased expression between T0 and T5 and 1 gene has reduced expression. The genes showing the greatest increase in expression following challenge (5.65 to 3.16 fold change) play an important role in (i) immune and inflammatory response (NFKB1, TNFAIP6, BASP1, IRF1, PLEK, BATF3); (ii) the regulation of innate resistance to pathogens (PTX3); and (iii) the regulation of cell metabolism (CYTH4, SLC2A6, ARG2). The genes with reduced expression (−1.5 to −2.5 fold) included genes involved in (i) lipid metabolism (ABCG2, FASN), (ii) chemokine, cytokine and intracellular signalling (SPPI), and (iii) cell cytoskeleton and extracellular matrix (KRT19). Conclusions: Analysis of genes with differential expression following infection showed an inverse relationship between immune response and lipid metabolism in the early response of the mammary gland to the S. aureus challenge. PTX3 showed a large change in expression in both milk and blood, and is therefore a candidate for further studies on immune response associated with mastitis. [ABSTRACT FROM AUTHOR]

Background: The existence of a genetic basis for host responses to bacterial intramammary infections has been widely documented, but the underlying mechanisms and the genes are still largely unknown. Previously, two divergent lines of sheep selected for high/low milk somatic cell scores have been shown to be respectively susceptible and resistant to intramammary infections by Staphylococcus spp. Transcriptional profiling with an 15K ovine-specific microarray of the milk somatic cells of susceptible and resistant sheep infected successively by S. epidermidis and S. aureus was performed in order to enhance our understanding of the molecular and cellular events associated with mastitis resistance. Results: The bacteriological titre was lower in the resistant than in the susceptible animals in the 48 hours following inoculation, although milk somatic cell concentration was similar. Gene expression was analysed in milk somatic cells, mainly represented by neutrophils, collected 12 hours post-challenge. A high number of differentially expressed genes between the two challenges indicated that more T cells are recruited upon inoculation by S. aureus than S. epidermidis. A total of 52 genes were significantly differentially expressed between the resistant and susceptible animals. Further Gene Ontology analysis indicated that differentially expressed genes were associated with immune and inflammatory responses, leukocyte adhesion, cell migration, and signal transduction. Close biological relationships could be established between most genes using gene network analysis. Furthermore, gene expression suggests that the cell turn-over, as a consequence of apoptosis/granulopoiesis, may be enhanced in the resistant line when compared to the susceptible line. Conclusions: Gene profiling in resistant and susceptible lines has provided good candidates for mapping the biological pathways and genes underlying genetically determined resistance and susceptibility towards Staphylococcus infections, and opens new fields for further investigation. [ABSTRACT FROM AUTHOR]

Mastitis caused by Escherichia coli and Staphylococcus aureus is a major pathology of dairy cows. To better understand the differential response of the mammary gland to these two pathogens, we stimulated bovine mammary epithelial cells (bMEC) with either E. coli crude lipopolysaccharide (LPS) or with S. aureus culture supernatant (SaS) to compare the transcriptomic profiles of the initial bMEC response. By using HEK 293 reporter cells for pattern recognition receptors, the LPS preparation was found to stimulate TLR2 and TLR4 but not TLR5, Nod1 or Nod2, whereas SaS stimulated TLR2. Biochemical analysis revealed that lipoteichoic acid, protein A and α-hemolysin were all present in SaS, and bMEC were found to be responsive to each of these molecules. Transcriptome profiling revealed a core innate immune response partly shared by LPS and SaS. However, LPS induced expression of a significant higher number of genes and the fold changes were of greater magnitude than those induced by SaS. Microarray data analysis suggests that the activation pathways and the early chemokine and cytokine production preceded the defense and stress responses. A major differential response was the activation of the type I IFN pathway by LPS but not by SaS. The higher upregulation of chemokines (Cxcl10, Ccl2, Ccl5 and Ccl20) that target mononuclear leucocytes by LPS than by SaS is likely to be related to the differential activation of the type I IFN pathway, and could induce a different profile of the initial recruitment of leucocytes. The MEC responses to the two stimuli were different, as LPS was associated with NF-κB and Fas signaling pathways, whereas SaS was associated with AP-1 and IL-17A signaling pathways. It is noteworthy that at the protein level secretion of TNF-α and IL-1β was not induced by either stimulus. These results suggest that the response of MEC to diffusible stimuli from E. coli and S. aureus contributes to the onset of the response with differential leucocyte recruitment and distinct inflammatory and innate immune reactions of the mammary gland to infection.

Genetic variability of mastitis resistance is well established in dairy cattle. Many studies focused on polygenic variation of the trait, by estimating heritabilities and genetic correlation among phenotypic traits related to mastitis such as somatic cell counts and clinical cases. The role of Major Histocompatibility Complex in the susceptibility or resistance to intrammamary infection is also well documented. Finally, development from molecular genome mapping led to accumulating information of quantitative trait loci (QTL) related to mastitis resistance and better understanding of the genetic determinism of the trait. From economic and genetic analyses, and according to welfare and food safety considerations and to breeders and consumer's concern, there is more and more evidence that mastitis should be included in breeding objective of dairy cattle breeds. Many countries have implemented selection for mastitis resistance based on linear decrease of somatic cell counts. Given biological questioning, potential unfavourable consequences for very low cell counts cows are regularly investigated. Improvement of selection accuracy for mastitis resistance is ongoing and includes: advances in modelling, optimal combination of mastitis related traits and associated predictors, such as udder morphology, definition of global breeding objective including production and functional traits, and inclusion of molecular information that is now available from QTL experiments.

Staphylococci are the main aetiological agents of small ruminants intramammary infections (IMI), the more frequent isolates being S. aureus in clinical cases and coagulase negative species in subclinical IMI. The clinical IMI, whose annual incidence is usually lower than 5%, mainly occur at the beginning of machine milking and during the first third of lactation. These features constitute small ruminant peculiarities compared to dairy cattle. Small ruminant mastitis is generally a chronic and contagious infection: the primary sources are mammary and cutaneous carriages, and spreading mainly occurs during milking. Somatic cell counts (SCC) represent a valuable tool for prevalence assessment and screening, but predictive values are better in ewes than in goats. Prevention is most often based on milking machine management, sanitation and annual control, and milking technique optimisation. Elimination mainly relies on culling animals exhibiting clinical, chronic and recurrent IMI, and on drying-off intramammary antibiotherapy; this treatment allows a good efficacy and may be used selectively by targeting infected udders only. Heritability values for lactation mean SCC scores are between 0.11 and 0.15. Effective inclusion of ewe's mastitis resistance in the breeding goal has recently been implemented in France following experimental and large scale estimations of genetic parameters for SCC scores.