Genomic prediction of blood biomarkers of metabolic disorders in Holstein cattle using parametric and nonparametric models.

BACKGROUND: Metabolic disturbances adversely impact productive and reproductive performance of dairy cattle due to changes in endocrine status and immune function, which increase the risk of disease. This may occur in the post-partum phase, but also throughout lactation, with sub-clinical symptoms. Recently, increased attention has been directed towards improved health and resilience in dairy cattle, and genomic selection (GS) could be a helpful tool for selecting animals that are more resilient to metabolic disturbances throughout lactation. Hence, we evaluated the genomic prediction of serum biomarkers levels for metabolic distress in 1353 Holsteins genotyped with the 100K single nucleotide polymorphism (SNP) chip assay. The GS was evaluated using parametric models best linear unbiased prediction (GBLUP), Bayesian B (BayesB), elastic net (ENET), and nonparametric models, gradient boosting machine (GBM) and stacking ensemble (Stack), which combines ENET and GBM approaches. RESULTS: The results show that the Stack approach outperformed other methods with a relative difference (RD), calculated as an increment in prediction accuracy, of approximately 18.0% compared to GBLUP, 12.6% compared to BayesB, 8.7% compared to ENET, and 4.4% compared to GBM. The highest RD in prediction accuracy between other models with respect to GBLUP was observed for haptoglobin (hapto) from 17.7% for BayesB to 41.2% for Stack; for Zn from 9.8% (BayesB) to 29.3% (Stack); for ceruloplasmin (CuCp) from 9.3% (BayesB) to 27.9% (Stack); for ferric reducing antioxidant power (FRAP) from 8.0% (BayesB) to 40.0% (Stack); and for total protein (PROTt) from 5.7% (BayesB) to 22.9% (Stack). Using a subset of top SNPs (1.5k) selected from the GBM approach improved the accuracy for GBLUP from 1.8 to 76.5%. However, for the other models reductions in prediction accuracy of 4.8% for ENET (average of 10 traits), 5.9% for GBM (average of 21 traits), and 6.6% for Stack (average of 16 traits) were observed. CONCLUSIONS: Our results indicate that the Stack approach was more accurate in predicting metabolic disturbances than GBLUP, BayesB, ENET, and GBM and seemed to be competitive for predicting complex phenotypes with various degrees of mode of inheritance, i.e. additive and non-additive effects. Selecting markers based on GBM improved accuracy of GBLUP.

Genetic legacy and adaptive signatures: investigating the history, diversity, and selection signatures in Rendena cattle resilient to eighteenth century rinderpest epidemics.

BACKGROUND: Rendena is a dual-purpose cattle breed, which is primarily found in the Italian Alps and the eastern areas of the Po valley, and recognized for its longevity, fertility, disease resistance and adaptability to steep Alpine pastures. It is categorized as 'vulnerable to extinction' with only 6057 registered animals in 2022, yet no comprehensive analyses of its molecular diversity have been performed to date. The aim of this study was to analyse the origin, genetic diversity, and genomic signatures of selection in Rendena cattle using data from samples collected in 2000 and 2018, and shed light on the breed's evolution and conservation needs. RESULTS: Genetic analysis revealed that the Rendena breed shares genetic components with various Alpine and Po valley breeds, with a marked genetic proximity to the Original Braunvieh breed, reflecting historical restocking efforts across the region. The breed shows signatures of selection related to both milk and meat production, environmental adaptation and immune response, the latter being possibly the result of multiple rinderpest epidemics that swept across the Alps in the eighteenth century. An analysis of the Rendena cattle population spanning 18 years showed an increase in the mean level of inbreeding over time, which is confirmed by the mean number of runs of homozygosity per individual, which was larger in the 2018 sample. CONCLUSIONS: The Rendena breed, while sharing a common origin with Brown Swiss, has developed distinct traits that enable it to thrive in the Alpine environment and make it highly valued by local farmers. Preserving these adaptive features is essential, not only for maintaining genetic diversity and enhancing the ability of this traditional animal husbandry to adapt to changing environments, but also for guaranteeing the resilience and sustainability of both this livestock system and the livelihoods within the Rendena valley.

Multiple genomic solutions for local adaptation in two closely related species (sheep and goats) facing the same climatic constraints.

The question of how local adaptation takes place remains a fundamental question in evolutionary biology. The variation of allele frequencies in genes under selection over environmental gradients remains mainly theoretical and its empirical assessment would help understanding how adaptation happens over environmental clines. To bring new insights to this issue we set up a broad framework which aimed to compare the adaptive trajectories over environmental clines in two domesticated mammal species co-distributed in diversified landscapes. We sequenced the genomes of 160 sheep and 161 goats extensively managed along environmental gradients, including temperature, rainfall, seasonality and altitude, to identify genes and biological processes shaping local adaptation. Allele frequencies at putatively adaptive loci were rarely found to vary gradually along environmental gradients, but rather displayed a discontinuous shift at the extremities of environmental clines. Of the 430 candidate adaptive genes identified, only 6 were orthologous between sheep and goats and those responded differently to environmental pressures, suggesting different putative mechanisms involved in local adaptation in these two closely related species. Interestingly, the genomes of the 2 species were impacted differently by the environment, genes related to signatures of selection were most related to altitude, slope and rainfall seasonality for sheep, and summer temperature and spring rainfall for goats. The diversity of candidate adaptive pathways may result from a high number of biological functions involved in the adaptations to multiple eco-climatic gradients, and a differential role of climatic drivers on the two species, despite their co-distribution along the same environmental gradients. This study describes empirical examples of clinal variation in putatively adaptive alleles with different patterns in allele frequency distributions over continuous environmental gradients, thus showing the diversity of genetic responses in adaptive landscapes and opening new horizons for understanding genomics of adaptation in mammalian species and beyond.

Integrating on-farm and genomic information improves the predictive ability of milk infrared prediction of blood indicators of metabolic disorders in dairy cows.

BACKGROUND: Blood metabolic profiles can be used to assess metabolic disorders and to evaluate the health status of dairy cows. Given that these analyses are time-consuming, expensive, and stressful for the cows, there has been increased interest in Fourier transform infrared (FTIR) spectroscopy of milk samples as a rapid, cost-effective alternative for predicting metabolic disturbances. The integration of FTIR data with other layers of information such as genomic and on-farm data (days in milk (DIM) and parity) has been proposed to further enhance the predictive ability of statistical methods. Here, we developed a phenotype prediction approach for a panel of blood metabolites based on a combination of milk FTIR data, on-farm data, and genomic information recorded on 1150 Holstein cows, using BayesB and gradient boosting machine (GBM) models, with tenfold, batch-out and herd-out cross-validation (CV) scenarios. RESULTS: The predictive ability of these approaches was measured by the coefficient of determination (R2). The results show that, compared to the model that includes only FTIR data, integration of both on-farm (DIM and parity) and genomic information with FTIR data improves the R2 for blood metabolites across the three CV scenarios, especially with the herd-out CV: R2 values ranged from 5.9 to 17.8% for BayesB, from 8.2 to 16.9% for GBM with the tenfold random CV, from 3.8 to 13.5% for BayesB and from 8.6 to 17.5% for GBM with the batch-out CV, and from 8.4 to 23.0% for BayesB and from 8.1 to 23.8% for GBM with the herd-out CV. Overall, with the model that includes the three sources of data, GBM was more accurate than BayesB with accuracies across the CV scenarios increasing by 7.1% for energy-related metabolites, 10.7% for liver function/hepatic damage, 9.6% for oxidative stress, 6.1% for inflammation/innate immunity, and 11.4% for mineral indicators. CONCLUSIONS: Our results show that, compared to using only milk FTIR data, a model integrating milk FTIR spectra with on-farm and genomic information improves the prediction of blood metabolic traits in Holstein cattle and that GBM is more accurate in predicting blood metabolites than BayesB, especially for the batch-out CV and herd-out CV scenarios.

The distribution of runs of homozygosity in the genome of river and swamp buffaloes reveals a history of adaptation, migration and crossbred events.

BACKGROUND: Water buffalo is one of the most important livestock species in the world. Two types of water buffalo exist: river buffalo (Bubalus bubalis bubalis) and swamp buffalo (Bubalus bubalis carabanensis). The buffalo genome has been recently sequenced, and thus a new 90 K single nucleotide polymorphism (SNP) bead chip has been developed. In this study, we investigated the genomic population structure and the level of inbreeding of 185 river and 153 swamp buffaloes using runs of homozygosity (ROH). Analyses were carried out jointly and separately for the two buffalo types. RESULTS: The SNP bead chip detected in swamp about one-third of the SNPs identified in the river type. In total, 18,116 ROH were detected in the combined data set (17,784 SNPs), and 16,251 of these were unique. ROH were present in both buffalo types mostly detected (~ 59%) in swamp buffalo. The number of ROH per animal was larger and genomic inbreeding was higher in swamp than river buffalo. In the separated datasets (46,891 and 17,690 SNPs for river and swamp type, respectively), 19,760 and 10,581 ROH were found in river and swamp, respectively. The genes that map to the ROH islands are associated with the adaptation to the environment, fitness traits and reproduction. CONCLUSIONS: Analysis of ROH features in the genome of the two water buffalo types allowed their genomic characterization and highlighted differences between buffalo types and between breeds. A large ROH island on chromosome 2 was shared between river and swamp buffaloes and contained genes that are involved in environmental adaptation and reproduction.

On the origin and diversification of Podolian cattle breeds: testing scenarios of European colonization using genome-wide SNP data.

BACKGROUND: During the Neolithic expansion, cattle accompanied humans and spread from their domestication centres to colonize the ancient world. In addition, European cattle occasionally intermingled with both indicine cattle and local aurochs resulting in an exclusive pattern of genetic diversity. Among the most ancient European cattle are breeds that belong to the so-called Podolian trunk, the history of which is still not well established. Here, we used genome-wide single nucleotide polymorphism (SNP) data on 806 individuals belonging to 36 breeds to reconstruct the origin and diversification of Podolian cattle and to provide a reliable scenario of the European colonization, through an approximate Bayesian computation random forest (ABC-RF) approach. RESULTS: Our results indicate that European Podolian cattle display higher values of genetic diversity indices than both African taurine and Asian indicine breeds. Clustering analyses show that Podolian breeds share close genomic relationships, which suggests a likely common genetic ancestry. Among the simulated and tested scenarios of the colonization of Europe from taurine cattle, the greatest support was obtained for the model assuming at least two waves of diffusion. Time estimates are in line with an early migration from the domestication centre of non-Podolian taurine breeds followed by a secondary migration of Podolian breeds. The best fitting model also suggests that the Italian Podolian breeds are the result of admixture between different genomic pools. CONCLUSIONS: This comprehensive dataset that includes most of the autochthonous cattle breeds belonging to the so-called Podolian trunk allowed us not only to shed light onto the origin and diversification of this group of cattle, but also to gain new insights into the diffusion of European cattle. The most well-supported scenario of colonization points to two main waves of migrations: with one that occurred alongside with the Neolithic human expansion and gave rise to the non-Podolian taurine breeds, and a more recent one that favoured the diffusion of European Podolian. In this process, we highlight the importance of both the Mediterranean and Danube routes in promoting European cattle colonization. Moreover, we identified admixture as a driver of diversification in Italy, which could represent a melting pot for Podolian cattle.

Runs of homozygosity in the Italian goat breeds: impact of management practices in low-input systems.

BACKGROUND: Climate and farming systems, several of which are considered as low-input agricultural systems, vary between goat populations from Northern and Southern Italy and have led to different management practices. These processes have impacted genome shaping in terms of inbreeding and regions under selection and resulted in differences between the northern and southern populations. Both inbreeding and signatures of selection can be pinpointed by the analysis of runs of homozygosity (ROH), which provides useful information to assist the management of this species in different rural areas. RESULTS: We analyzed the ROH distribution and inbreeding (FROH) in 902 goats from the Italian Goat Consortium2 dataset. We evaluated the differences in individual ROH number and length between goat breeds from Northern (NRD) and Central-southern (CSD) Italy. Then, we identified the signatures of selection that differentiate these two groups using three methods: ROH, ΔROH, and averaged FST. ROH analyses showed that some Italian goat breeds have a lower inbreeding coefficient, which is attributable to their management and history. ROH are longer in breeds that are undergoing non-optimal management or with small population size. In several small breeds, the ROH length classes are balanced, reflecting more accurate mating planning. The differences in climate and management between the NRD and CSD groups have resulted in different ROH lengths and numbers: the NRD populations bred in isolated valleys present more and shorter ROH segments, while the CSD populations have fewer and longer ROH, which is likely due to the fact that they have undergone more admixture events during the horizontal transhumance practice followed by a more recent standardization. We identified four genes within signatures of selection on chromosome 11 related to fertility in the NRD group, and 23 genes on chromosomes 5 and 6 related to growth in the CSD group. Finally, we identified 17 genes on chromosome 12 related to environmental adaptation and body size with high homozygosity in both groups. CONCLUSIONS: These results show how different management practices have impacted the level of genomic inbreeding in two Italian goat groups and could be useful to assist management in a low-input system while safeguarding the diversity of small populations.

Genomic prediction for latent variables related to milk fatty acid composition in Holstein, Simmental and Brown Swiss dairy cattle breeds.

Genomic selection (GS) reports on milk fatty acid (FA) profiles have been published quite recently and are still few despite this trait represents the most important aspect of milk nutritional and sensory quality. Reasons for this can be found in the high costs of phenotype recording but also in issues related to its nature of complex trait constituted by multiple genetically correlated variables with low heritabilities. One possible strategy to deal with such constraint is represented by the use of dimension reduction methods. We analysed 40 individual FAs from Italian Brown Swiss, Holstein and Simmental milk through multivariate factor analysis (MFA) to study the genetics of milk FA-related latent variables (factors) and assess their potential use in breeding. A total of nine factors were obtained, and their genetic parameters were inferred under a Bayesian framework using two statistical approaches: the classical pedigree best linear unbiased prediction (ABLUP) and the single-step genomic BLUP (ssGBLUP). The resulting factorial solutions were able to represent groups of FAs with common origin and function and can be considered concise pathway-level phenotypes. The heritability (h2 ) values showed relevant variations across different factors in each breed (0.03 ≤ h2  ≤ 0.38). The accuracies of breeding values predicted were low to high, ranging from 0.13 to 0.72 and from 0.18 to 0.74 considering the pedigree and the genomic model, respectively. The gain in accuracy in genetic prediction due to the addition of genomic information was ~30% and ~5% in validation and training groups respectively, confirming the contribution of genomic information in yielding more accurate predictions compared to the traditional ABLUP methodology. Our results suggest that MFA in combination with GS can be a valuable tool in dairy cattle breeding and deserves to be further investigated for use in future breeding programs to improve cow's milk FA-related traits.

Evaluation of circulating leukocyte transcriptome and its relationship with immune function and blood markers in dairy cows during the transition period.

Dairy cows during the transition period are faced with important physiological changes which include a dysfunctional immune system and an increased inflammatory state. New data are necessary to understand the key factors involved in the immune system regulation. Six dairy cows were sampled during transition period to investigate the leukocyte transcriptome changes and its relationship with blood biomarkers. Blood samples were collected at - 20 ± 2, - 3 ± 1, 3, and 7 days from parturition (DFP). Leukocyte transcriptome was analyzed by deep sequencing technology (Hiseq1000 Illumina, USA). Plasma was analyzed for metabolic biomarkers. Differentially expressed genes (DEG) were used to run an enrichment analysis through the Dynamic Impact Approach (DIA). Considering - 20 DFP as references time, the main KEGG impacted pathways were activated before calving (- 3 DFP) and were connected to lipid metabolism, lipid transport in plasma, and phagosome. The greatest differences were found after parturition with 281 DEG (179 upregulated and 102 downregulated). The activated pathways were mainly related to immunity and endocrine aspects, while metabolic pathways related to lipid and amino acid metabolism were inhibited. Plasma BHBA had a substantial inhibitory impact on KEGG pathways related to DNA replication and cell cycle, while plasma IL-1ß had an inhibitory impact on fatty acid elongation in mitochondria and an activated impact in several pathways related to cellular energy metabolism. Overall, this study confirmed that many changes in lipid metabolism and immune competence of the circulating leukocytes occurred in dairy cow around calving. Interestingly, BHBA and IL-1ß connected with the transcriptome.

Maternal peri-conceptional undernourishment perturbs offspring sperm methylome.

The genotype of an organism is stable throughout its life; however, its epigenome is dynamic and can be altered in response to environmental factors, such as diet. Inheritance of acquired epigenetic modifications by the next generation occurs through the germline, although the precise mechanisms remain to be elucidated. Here, we used a sheep model to evaluate if modification of the maternal diet (CTR; control, UND: undernutrition; FA: undernutrition and folic acid supplementation) during the peri-conceptional period affects the genome-wide methylation status of the gametes of male offspring. Sperm DNA methylation, measured by Reduced Representation Bisulfite Sequencing (RRBS), identified Differentially Methylated Regions (DMR) in offspring that experienced in utero undernutrition, both in UND (244) and FA (240), compared with CTR. Gene ontology (GO) analysis identified DMRs in categories related to sperm function, therefore we investigated whether the fertilizing capacity of the semen from the three groups differed in an in vitro fertilization assay. Spermatozoa from the undernourished groups showed lower motility and sperm chromatin structure abnormalities, represented by a higher percentage of DNA fragmentation and an increased number of immature cells, compared with CTR. While good quality blastocysts were obtained from all three groups, the proportion of embryos reaching the blastocyst stage was reduced in the UND vs CTR, an effect partially rescued by the FA treatment. The data reported here show that nutritional stress during early pregnancy leads to epigenetic modifications in the semen of the resulting offspring, the effects of which in next generation remain to be elucidated.

Untargeted metabolomic profiling of accessory sex gland fluid from Morada Nova rams.

The present study was conducted to characterize the metabolome of accessory gland fluid (AGF) of locally adapted Morada Nova rams, raised in the Brazilian Northeast. AGF was collected by an artificial vagina from five vasectomized rams. Metabolites were identified by gas chromatography-mass spectrometry (GC/MS) and high-performance liquid chromatography-mass spectrometry (LC/MS), with the support of Human Metabolome Database, PubChem, LIPID Metabolites, Pathways Strategy databases, and MetaboAnalyst platforms. There were 182 and 190 metabolites detected by GC/MS and LC/MS, respectively, with an overlap of one molecule. Lipids and lipid-like molecules were the most abundant class of metabolites in the ram AGF (127 compounds), followed by amino acids, peptides, and analogs(103 metabolites). Considering all GC/MS and LC/MS, fructose, glycerol, citric acid, d-mannitol, d-glucose, and l-(+)-lactic acid were the most abundant single metabolites present in the ram AGF. Meaningful pathways associated with AGF metabolites included glycine, serine and threonine metabolism; pantothenate and CoA biosynthesis; galactose metabolism; glutamate metabolism and phenylalanine metabolism, and so forth. In conclusion, the combined use of LC/MS and GC/MS was essential for getting a holistic view of the compounds embedded in the ram AGF. Chemical analysis of the accessory sex gland secretion is relevant for understanding sperm function and fertilization.

Occurrence, biological properties and potential effects on human health of ß-casomorphin 7: Current knowledge and concerns.

The genetic variant A1 of bovine ß-casein (ß-Cn) presents a His residue at a position 67 of the mature protein. This feature makes the Ile66-His67 bond more vulnerable to enzymatic cleavage, determining the release of the peptide ß-Cn f(60-66), named ß-casomorphin 7 (BCM7). BCM7 is an opioid-agonist for µ receptors, and it has been hypothesized to be involved in the development of different non-transmissible diseases in humans. In the last decade, studies have provided additional results on the potential health impact of ß-Cn A1 and BCM7. These studies, here reviewed, highlighted a relation between the consumption of ß-Cn A1 (and its derivative BCM7) and the increase of inflammatory response as well as discomfort at the gastrointestinal level. Conversely, the role of BCM7 and the effects of ingestion of ß-Cn A1 on the onset or worsening of other non-transmissible diseases as caused or favored by still need proof of evidence. Overall, the reviewed literature demonstrates that the "ß-Cn A1/BCM7 issue" remains an intriguing but not exhaustively explained topic in human nutrition. On this basis, policies in favor of breeding for ß-Cn variants not releasing BCM7 and consumption of "A1-like" milk appear not yet sound for a healthier and safer nutrition.

On the origin of European sheep as revealed by the diversity of the Balkan breeds and by optimizing population-genetic analysis tools.

BACKGROUND: In the Neolithic, domestic sheep migrated into Europe and subsequently spread in westerly and northwesterly directions. Reconstruction of these migrations and subsequent genetic events requires a more detailed characterization of the current phylogeographic differentiation. RESULTS: We collected 50 K single nucleotide polymorphism (SNP) profiles of Balkan sheep that are currently found near the major Neolithic point of entry into Europe, and combined these data with published genotypes from southwest-Asian, Mediterranean, central-European and north-European sheep and from Asian and European mouflons. We detected clines, ancestral components and admixture by using variants of common analysis tools: geography-informative supervised principal component analysis (PCA), breed-specific admixture analysis, across-breed [Formula: see text] profiles and phylogenetic analysis of regional pools of breeds. The regional Balkan sheep populations exhibit considerable genetic overlap, but are clearly distinct from the breeds in surrounding regions. The Asian mouflon did not influence the differentiation of the European domestic sheep and is only distantly related to present-day sheep, including those from Iran where the mouflons were sampled. We demonstrate the occurrence, from southeast to northwest Europe, of a continuously increasing ancestral component of up to 20% contributed by the European mouflon, which is assumed to descend from the original Neolithic domesticates. The overall patterns indicate that the Balkan region and Italy served as post-domestication migration hubs, from which wool sheep reached Spain and north Italy with subsequent migrations northwards. The documented dispersal of Tarentine wool sheep during the Roman period may have been part of this process. Our results also reproduce the documented 18th century admixture of Spanish Merino sheep into several central-European breeds. CONCLUSIONS: Our results contribute to a better understanding of the events that have created the present diversity pattern, which is relevant for the management of the genetic resources represented by the European sheep population.

Epigenetic analysis of high and low motile sperm populations reveals methylation variation in satellite regions within the pericentromeric position and in genes functionally related to sperm DNA organization and maintenance in Bos taurus.

BACKGROUND: Sperm epigenetics is an emerging area of study supported by observations reporting that abnormal sperm DNA methylation patterns are associated with infertility. Here, we explore cytosine-guanine dinucleotides (CpGs) methylation in high (HM) and low motile (LM) Bos taurus sperm populations separated by Percoll gradient. HM and LM methylation patterns were investigated by bisulfite sequencing. RESULTS: Comparison between HM and LM sperm populations revealed that methylation variation affects genes involved in chromatin organization. CpG Islands (CGIs), were highly remodelled. A high proportion of CGIs was found to be methylated at low/intermediate level (20-60%) and associated to the repetitive element BTSAT4 satellite. The low/intermediate level of methylation in BTSAT4 was stably maintained in pericentric regions of chromosomes. BTSAT4 was hypomethylated in HM sperm populations. CONCLUSIONS: The characterization of the epigenome in HM and LM Bos taurus sperm populations provides a first step towards the understanding of the effect of methylation on sperm fertility. Methylation variation observed in HM and LM populations in genes associated to DNA structure remodelling as well as in a repetitive element in pericentric regions suggests that maintenance of chromosome structure through epigenetic regulation is probably crucial for correct sperm functionality.

Gene co-expression networks in liver and muscle transcriptome reveal sex-specific gene expression in lambs fed with a mix of essential oils.

BACKGROUND: Essential oil (EO) dietary supplementation is a new strategy to improve animal health. EO compounds have antiparasitic, antimicrobial, antiviral, antimycotic, antioxidant and anti-inflammatory proprieties. Nutrigenomics investigations represent innovative approaches in understanding the relation between diet effect and gene expression related to the animal performance. Few nutrigenomics studies have used a high-throughput RNA-Sequencing (RNA-Seq) approach, despite great potential of RNA-Seq data in gene expression quantification and in co-expression network analyses. Our aim is to use the potential of RNA-Sequencing data in order to evaluate the effect of an EO supplementary diet on gene expression in both lamb liver and muscle. RESULTS: Using a treatment and sex interaction model, 13 and 4 differentially expressed genes were identified in liver and muscle respectively. Sex-specific differentially expressed (DE) genes were identified in both sexes. Using network based analysis, different clusters of co-expressed genes that were highly correlated to the diet were detected in males vs. females, in agreement with DE analysis. A total of five regulatory genes in liver tissue associated to EO diet were identified: DNAJB9, MANF, UFM1, CTNNLA1 and NFX1. Our study reveals a sex-dependent effect of EO diet in both tissues, and an influence on the expression of genes mainly involved in immune, inflammatory and stress pathway. CONCLUSION: Our analysis suggests a sex-dependent effect of the EO dietary supplementation on the expression profile of both liver and muscle tissues. We hypothesize that the presence of EOs could have beneficial effects on wellness of male lamb and further analyses are needed to understand the biological mechanisms behind the different effect of EO metabolites based on sex. Using lamb as a model for nutrigenomics studies, it could be interesting to investigate the effects of EO diets in other species and in humans.

Genome-wide SNP profiling of worldwide goat populations reveals strong partitioning of diversity and highlights post-domestication migration routes.

BACKGROUND: Goat populations that are characterized within the AdaptMap project cover a large part of the worldwide distribution of this species and provide the opportunity to assess their diversity at a global scale. We analysed genome-wide 50 K single nucleotide polymorphism (SNP) data from 144 populations to describe the global patterns of molecular variation, compare them to those observed in other livestock species, and identify the drivers that led to the current distribution of goats. RESULTS: A high degree of genetic variability exists among the goat populations studied. Our results highlight a strong partitioning of molecular diversity between and within continents. Three major gene pools correspond to goats from Europe, Africa and West Asia. Dissection of sub-structures disclosed regional gene pools, which reflect the main post-domestication migration routes. We also identified several exchanges, mainly in African populations, and which often involve admixed and cosmopolitan breeds. Extensive gene flow has taken place within specific areas (e.g., south Europe, Morocco and Mali-Burkina Faso-Nigeria), whereas elsewhere isolation due to geographical barriers (e.g., seas or mountains) or human management has decreased local gene flows. CONCLUSIONS: After domestication in the Fertile Crescent in the early Neolithic era (ca. 12,000 YBP), domestic goats that already carried differentiated gene pools spread to Europe, Africa and Asia. The spread of these populations determined the major genomic background of the continental populations, which currently have a more marked subdivision than that observed in other ruminant livestock species. Subsequently, further diversification occurred at the regional level due to geographical and reproductive isolation, which was accompanied by additional migrations and/or importations, the traces of which are still detectable today. The effects of breed formation were clearly detected, particularly in Central and North Europe. Overall, our results highlight a remarkable diversity that occurs at the global scale and is locally partitioned and often affected by introgression from cosmopolitan breeds. These findings support the importance of long-term preservation of goat diversity, and provide a useful framework for investigating adaptive introgression, directing genetic improvement and choosing breeding targets.

Conservation status and historical relatedness of Italian cattle breeds.

BACKGROUND: In the last 50 years, the diversity of cattle breeds has experienced a severe contraction. However, in spite of the growing diffusion of cosmopolite specialized breeds, several local cattle breeds are still farmed in Italy. Genetic characterization of breeds represents an essential step to guide decisions in the management of farm animal genetic resources. The aim of this work was to provide a high-resolution representation of the genome-wide diversity and population structure of Italian local cattle breeds using a medium-density single nucleotide polymorphism (SNP) array. RESULTS: After quality control filtering, the dataset included 31,013 SNPs for 800 samples from 32 breeds. Our results on the genetic diversity of these breeds agree largely with their recorded history. We observed a low level of genetic diversity, which together with the small size of the effective populations, confirmed that several breeds are threatened with extinction. According to the analysis of runs of homozygosity, evidence of recent inbreeding was strong in some local breeds, such as Garfagnina, Mucca Pisana and Pontremolese. Patterns of genetic differentiation, shared ancestry, admixture events, and the phylogenetic tree, all suggest the presence of gene flow, in particular among breeds that originate from the same geographical area, such as the Sicilian breeds. In spite of the complex admixture events that most Italian cattle breeds have experienced, they have preserved distinctive characteristics and can be clearly discriminated, which is probably due to differences in genetic origin, environment, genetic isolation and inbreeding. CONCLUSIONS: This study is the first exhaustive genome-wide analysis of the diversity of Italian cattle breeds. The results are of significant importance because they will help design and implement conservation strategies. Indeed, efforts to maintain genetic diversity in these breeds are needed. Improvement of systems to record and monitor inbreeding in these breeds may contribute to their in situ conservation and, in view of this, the availability of genomic data is a fundamental resource.

Identification of additional loci associated with antibody response to Mycobacterium avium ssp. Paratuberculosis in cattle by GSEA-SNP analysis.

Mycobacterium avium subsp. paratuberculosis: (MAP) causes a contagious chronic infection results in Johne's disease in a wide range of animal species, including cattle. Several genome-wide association studies (GWAS) have been carried out to identify loci putatively associated with MAP susceptibility by testing each marker separately and identifying SNPs that show a significant association with the phenotype, while SNP with modest effects are usually ignored. The objective of this study was to identify modest-effect genes associated with MAP susceptibility using a pathway-based approach. The Illumina BovineSNP50 BeadChip was used to genotype 966 Holstein cows, 483 positive and 483 negative for antibody response to MAP, data were then analyzed using novel SNP-based Gene Set Enrichment Analysis (GSEA-SNP) and validated with Adaptive Rank Truncated Product methodology. An allele-based test was carried out to estimate the statistical association for each marker with the phenotype, subsequently SNPs were mapped to the closest genes, considering for each gene the single variant with the highest value within a window of 50 kb, then pathway-statistics were tested using the GSEA-SNP method. The GO biological process "embryogenesis and morphogenesis" was most highly associated with antibody response to MAP. Within this pathway, five genes code for proteins which play a role in the immune defense relevant to response to bacterial infection. The immune response genes identified would not have been considered using a standard GWAS, thus demonstrating that the pathway approach can extend the interpretation of genome-wide association analyses and identify additional candidate genes for target traits.

The Valdostana goat: a genome-wide investigation of the distinctiveness of its selective sweep regions.

The Valdostana goat is an alpine breed, raised only in the northern Italian region of the Aosta Valley. This breed's main purpose is to produce milk and meat, but is peculiar for its involvement in the "Batailles de Chèvres," a recent tradition of non-cruel fight tournaments. At both the genetic and genomic levels, only a very limited number of studies have been performed with this breed and there are no studies about the genomic signatures left by selection. In this work, 24 unrelated Valdostana animals were screened for runs of homozygosity to identify highly homozygous regions. Then, six different approaches (ROH comparison, Fst single SNPs and windows based, Bayesian, Rsb, and XP-EHH) were applied comparing the Valdostana dataset with 14 other Italian goat breeds to confirm regions that were different among the comparisons. A total of three regions of selection that were also unique among the Valdostana were identified and located on chromosomes 1, 7, and 12 and contained 144 genes. Enrichment analyses detected genes such as cytokines and lymphocyte/leukocyte proliferation genes involved in the regulation of the immune system. A genetic link between an aggressive challenge, cytokines, and immunity has been hypothesized in many studies both in humans and in other species. Possible hypotheses associated with the signals of selection detected could be therefore related to immune-related factors as well as with the peculiar battle competition, or other breed-specific traits, and provided insights for further investigation of these unique regions, for the understanding and safeguard of the Valdostana breed.

GHap: an R package for genome-wide haplotyping.

UNLABELLED: The GHap R package was designed to call haplotypes from phased marker data. Given user-defined haplotype blocks (HapBlock), the package identifies the different haplotype alleles (HapAllele) present in the data and scores sample haplotype allele genotypes (HapGenotype) based on HapAllele dose (i.e. 0, 1 or 2 copies). The output is not only useful for analyses that can handle multi-allelic markers, but is also conveniently formatted for existing pipelines intended for bi-allelic markers. AVAILABILITY AND IMPLEMENTATION: https://cran.r-project.org/package=GHap CONTACT: ytutsunomiya@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.