Genome-wide association study provides insights into genes related with horn development in Nelore beef cattle.

Abstract The causal mutation for polledness in Nelore (Bos taurus indicus) breed seems to have appeared first in Brazil in 1957. The expression of the polled trait is known to be ruled by a few groups of alleles in taurine breeds; however, the genetic basis of this trait in indicine cattle is still unclear. The aim of this study was to identify genomic regions associated with the hornless trait in a commercial Nelore population. A total of 107,294 animals had phenotypes recorded and 2,238 were genotyped/imputed for 777k SNP. The weighted single-step approach for genome-wide association study (WssGWAS) was used to estimate the SNP effects and variances accounted for by 1 Mb sliding SNP windows. A centromeric region of chromosome 1 with 3.11 Mb size (BTA1: 878,631?3,987,104 bp) was found to be associated with hornless in the studied population. A total of 28 protein-coding genes are mapped in this region, including the taurine Polled locus and the IFNAR1, IFNAR2, IFNGR2, KRTAP11-1, MIS18A, OLIG1, OLIG2, and SOD1 genes, which expression can be related to the horn formation as described in literature. The functional enrichment analysis by DAVID tool revealed cytokine-cytokine receptor interaction, JAK-STAT signaling, natural killer cell mediated cytotoxicity, and osteoclast differentiation pathways as significant (P < 0.05). In addition, a runs of homozygosity (ROH) analysis identified a ROH island in polled animals with 2.47 Mb inside the region identified by WssGWAS. Polledness in Nelore cattle is associated with one region in the genome with 3.1 Mb size in chromosome 1. Several genes are harbored in this region, and they may act together in the determination of the polled/horned phenotype. Fine mapping the locus responsible for polled trait in Nelore breed and the identification of the molecular mechanisms regulating the horn growth deserve further investigation

Autozygosity islands and ROH patterns in Nellore lineages: evidence of selection for functionally important traits.

Abstract Background The aim of this study was to assess genome-wide autozygosity in a Nellore cattle population and to characterize ROH patterns and autozygosity islands that may have occurred due to selection within its lineages. It attempts also to compare estimates of inbreeding calculated from ROH (FROH), genomic relationship matrix (FGRM), and pedigree-based coefficient (FPED). Results The average number of ROH per animal was 55.15&#8201;±&#8201;13.01 with an average size of 3.24 Mb. The Nellore genome is composed mostly by a high number of shorter segments accounting for 78% of all ROH, although the proportion of the genome covered by them was relatively small. The genome autozygosity proportion indicates moderate to high inbreeding levels for classical standards, with an average value of 7.15% (178.70 Mb). The average of FPED and FROH, and their correlations (&#8722;&#8201;0.05 to 0.26) were low. Estimates of correlation between FGRM-FPED was zero, while the correlation (&#8722;&#8201;0.01 to &#8722;&#8201;0.07) between FGRM-FROH decreased as a function of ROH length, except for FROH&#8201;>&#8201;8Mb (&#8722;&#8201;0.03). Overall, inbreeding coefficients were not high for the genotyped animals. Autozygosity islands were evident across the genome (n&#8201;=&#8201;62) and their genomic location did not largely differ within lineages. Enriched terms (p&#8201;<&#8201;0.01) associated with defense response to bacteria (GO:0042742), immune complex reaction (GO:0045647), pregnancy-associated glycoproteins genes (GO:0030163), and organism growth (GO:0040014) were described within the autozygotic islands. Conclusions Low FPED-FROH correlation estimates indicate that FPED is not the most suitable method for capturing ancient inbreeding when the pedigree does not extend back many generations and FROH should be used instead. Enriched terms (p <&#8201;0.01) suggest a strong selection for immune response. Non-overlapping islands within the lineages greatly explain the mechanism underlying selection for functionally important traits in Nellore cattle

Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection

Members of the Toll-like receptor (TLR) gene family occupy key roles in the mammalian innate immune system by functioning as sentries for the detection of invading pathogens, thereafter provoking host innate immune responses. We utilized a custom next-generation sequencing approach and allele-specific genotyping assays to detect and validate 280 biallelic variants across all 10 bovine TLR genes, including 71 nonsynonymous single nucleotide polymorphisms (SNPs) and one putative nonsense SNP. Bayesian haplotype reconstructions and median joining networks revealed haplotype sharing between Bos taurus taurus and Bos taurus indicus breeds at every locus, and specialized beef and dairy breeds could not be differentiated despite an average polymorphism density of 1 marker/158 bp. Collectively, 160 tagSNPs and two tag insertion-deletion mutations (indels) were sufficient to predict 100% of the variation at 280 variable sites for both Bos subspecies and their hybrids, whereas 118 tagSNPs and 1 tagIndel predictively captured 100% of the variation at 235 variable sites for B. t. taurus. Polyphen and SIFT analyses of amino acid (AA) replacements encoded by bovine TLR SNPs indicated that up to 32% of the AA substitutions were expected to impact protein function. Classical and newly developed tests of diversity provide strong support for balancing selection operating on TLR3 and TLR8, and purifying selection acting on TLR10. An investigation of the persistence and continuity of linkage disequilibrium (r2≥0.50) between adjacent variable sites also supported the presence of selection acting on TLR3 and TLR8. A case-control study employing validated variants from bovine TLR genes recognizing bacterial ligands revealed six SNPs potentially eliciting small effects on susceptibility to Mycobacterium avium spp paratuberculosis infection in dairy cattle. The results of this study will broadly impact domestic cattle research by providing the necessary foundation to explore several avenues of bovine translational genomics, and the potential for marker-assisted vaccination

Ghrelin Stimulation of Growth Hormone-Releasing Hormone Neurons Is Direct in the Arcuate Nucleus

International audienceGhrelin targets the arcuate nucleus, from where growth hormone releasing hormone (GHRH) neurones trigger GH secretion. This hypothalamic nucleus also contains neuropeptide Y (NPY) neurons which play a master role in the effect of ghrelin on feeding. Interestingly, connections between NPY and GHRH neurons have been reported, leading to the hypothesis that the GH axis and the feeding circuits might be co-regulated by ghrelin.Here, we show that ghrelin stimulates the firing rate of identified GHRH neurons, in transgenic GHRH-GFP mice. This stimulation is prevented by growth hormone secretagogue receptor-1 antagonism as well as by U-73122, a phospholipase C inhibitor and by calcium channels blockers. The effect of ghrelin does not require synaptic transmission, as it is not antagonized by gamma-aminobutyric acid, glutamate and NPY receptor antagonists. In addition, this hypothalamic effect of ghrelin is independent of somatostatin, the inhibitor of the GH axis, since it is also found in somatostatin knockout mice. Indeed, ghrelin does not modify synaptic currents of GHRH neurons. However, ghrelin exerts a strong and direct depolarizing effect on GHRH neurons, which supports their increased firing rate. Thus, GHRH neurons are a specific target for ghrelin within the brain, and not activated secondary to altered activity in feeding circuits. These results support the view that ghrelin related therapeutic approaches could be directed separately towards GH deficiency or feeding disorders

Caracterização do desequilíbrio de ligação em uma população de bovinos da raça Nelore.

Resumo: Tendo em vista a importância da estimação do desequilíbrio de ligação para a seleção genômica, o objetivo deste estudo foi estimar o desequilíbrio de ligação de uma população de bovinos da raça Nelore participantes do programa de melhoramento da ANCP. Foram utilizadas informações de 9.459 animais genotipados com um painel de alta densidade, totalizando 735.044 SNP?s, antes do controle de qualidade. A estimação do desequilíbrio de ligação foi realizada através do programa SNP1101. Os valores de LD observados para os cromossomos autossômicos variaram de 0,18 a 0,25. Para marcadores distanciados até 1 Kb a média de r² foi de 0,53 e para marcadores distanciados entre 90 e 100 Kb 0,14. Para MAF a média variou de 0,23 a 0,25, considerando MAF mínimo de 5%. Os resultados obtidos neste estudo indicam que, a densidade de marcadores utilizados foi capaz de detectar altos níveis de LD. Adicionalmente, conclui-se que marcadores distanciados até 50 Kb ainda detectam consideráveis níveis de LD. Abstract: Considering the importance of estimating linkage disequilibrium for genomic selection, the objective of this study was to estimate the linkage disequilibrium in a population of Nellore cattle participating in the ANCP breeding program. Information from 9,396 genotyped animals with a high density panel, totaling 735,044 SNP's before quality control were used. The estimation of linkage dissequilibrium (LD) was performed using the SNP1101 program. The mean LD values observed for the autosomal chromosomes ranged from 0.18 to 0.25. For markers distanced lower than 1 Kb the r² mean was 0.53, and for markers distanced between 90 and 100 Kb was 0.14. For MAF, the mean ranged from 0.23 to 0.25, a minimum MAF of 0.05 was considered. The results obtained in this study indicated that the density of markers used was able to detect high levels of LD. Additionally, for markers distanced up to 50 Kb, considerable levels of LD was detected

An updated view of hypothalamic-vascular-pituitary unit function and plasticity

The discoveries of novel functional adaptations of the hypothalamus and anterior pituitary gland for physiological regulation have transformed our understanding of their interaction. The activity of a small proportion of hypothalamic neurons can control complex hormonal signalling, which is disconnected from a simple stimulus and the subsequent hormone secretion relationship and is dependent on physiological status. The interrelationship of the terminals of hypothalamic neurons and pituitary cells with the vasculature has an important role in determining the pattern of neurohormone exposure. Cells in the pituitary gland form networks with distinct organizational motifs that are related to the duration and pattern of output, and modifications of these networks occur in different physiological states, can persist after cessation of demand and result in enhanced function. Consequently, the hypothalamus and pituitary can no longer be considered as having a simple stratified relationship: with the vasculature they form a tripartite system, which must function in concert for appropriate hypothalamic regulation of physiological processes, such as reproduction. An improved understanding of the mechanisms underlying these regulatory features has implications for current and future therapies that correct defects in hypothalamic–pituitary axes. In addition, recapitulating proper network organization will be an important challenge for regenerative stem cell treatment

A Method to Compare the Thermal Shock Resistances and the Severity of Quenching Conditions of Brittle Solids

The thermal shock behavior and resistance of brittle materials are mostly investigated through the determination of a critical quenching temperature difference, $\Delta T_{\rm c}$. This technique, however, needs a large number of, almost, identical samples and is thus poorly adapted to products being in the stage of research and development. In order to overcome this difficulty, the indentation technique has been used in this work. The residual contact stresses, created during indentation, permit a stage of stable extension of the indentation cracks under the action of further stressing. The relative increase of radial crack length as a function of Vickers indentation load, $c/c_0$ $vs$. $P$, is taken as a criterion, or indicator, of relative thermal shock resistance, or of the severities of quenching conditions. This is validated, first in quenching materials whose empirical ranking is well established, and second in varying parameters of the Biot number. Finally, are two batches of a functional ceramic compared. The proposed criterion reflects the competition between the toughness of the quenched material, as an intrinsic property, and the thermal transient stresses, as a consequence of the physical properties of both the quenched sample and the quenching medium. Possibilities for extending the developed approach towards a more accurate description of quenching phenomena and stress states such as to refine theoretical models are discussed.La détermination d'une différence de température critique, $\Delta T_{\rm c}$, est la technique la plus souvent utilisée dans l'étude de la résistance et du comportement au choc thermique des matériaux fragiles. Elle nécessite cependant un grand nombre d'échantillons, presque identiques et est donc peu adaptée aux produits dans le stade de recherche et développement. Afin de lever cet obstacle, la méthode de l'indentation de dureté est utilisée dans ce travail. L'indentation crée des contraintes résiduelles de contact qui permettent une extension stable des fissures d'indentation pendant une sollicitation ultérieure. L'accroissement relatif de la longueur des fissures radiales en fonction de la charge d'indentation Vickers, $c/c_0$ $vs$. $P$, est ainsi proposé comme critère, ou indicateur, de la résistance relative au choc thermique ou de la sévérité des conditions de trempe. Ce critère est validé, premièrement en trempant des matériaux dont la résistance relative est établie et deuxièmement, en faisant varier des paramètres du nombre de Biot. Finalement, nous comparons deux céramiques fonctionnelles. Le critère proposé rend compte de la résistance à la fissuration du matériau, en tant que propriété intrinsèque, et de la contrainte thermique transitoire résultant des propriétés physiques à la fois de l'échantillon et du milieu de trempe. Nous évoquons finalement les possibilités d'utiliser cette démarche aux fins d'une description précise du phénomène de trempe et des contraintes qui en résultent, pour affiner les modèles existants

CREEP OF HOT-PRESSED SiC-Al MATERIALS

Deux nuances de SiC-Al pressées à chaud (avec 0.3% et 1.5% d'additifs) ont été déformées en flexion trois points dans le domaine de températures 1300°C - 1750°C. Elles ont la même taille de grains, mais les observations fractographiques montrent que les joints de grains sont de nature et de résistance différentes. L'effet résultant est un tracé d'Arrhénius courbe, pour l'une des deux nuances. La forme particulière du tracé d'Arrhénius est expliquée en considérant une contribution mécanique et athermique à la cavitation. Les mécanismes de fluage de base sont soit de la diffusion, soit de la dissolution-reprécipitation.Two batches of hot-pressed SiC-Al materials (0.3% and 1.5% additives) have been deformed in three points bending in the temperature range 1300°C - 1750°C. They have the same grain sizes, but fractographic investigations show that the grain boundaries are of different nature and strength. The resulting effect is a curved Arrhenius plot for one of the grades. The special shape of the Arrhenius plot is explained taking a mechanical and athermal contribution to the cavitation process into account. The basic creep mechanism is shown to be either diffusion or dissolution-reprecipitation