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To fine map a quantitative trait locus (QTL) affecting milk production traits previously associated with microsatellite RM188, we implemented an interval mapping analysis by using microsatellite markers in a large Israeli Holstein half-sib sire family, and linkage disequilibrium (LD) mapping in a large set of US Holstein bulls. Interval mapping located the target QTL to the near vicinity of RM188. For the LD mapping, we identified 42 single nucleotide polymorphisms (SNP) in 15 genes in a 12-Mb region on bovine chromosome 4. A total of 24 tag SNP were genotyped in 882 bulls belonging to the University of California Davis archival collection of Holstein bull DNA samples with predicted transmitted ability phenotypes. Marker-to-marker LD analysis revealed 2 LD blocks, with intrablock r² values of 0.10 and 0.46, respectively; outside the blocks, r² values ranged from 0.002 to 0.23. A standard additive/ dominance model using the generalized linear model procedure of SAS and the regression module of HelixTree software were used to test marker-trait associations. Single nucleotide polymorphism 9 on ARL4A, SNP10 on XR_027435.1, SNP12 on ETV1, SNP21 on SNX13, and SNP24 were significantly associated with milk production traits. We propose the interval encompassing ARL4A and SNX13 genes as a candidate region in bovine chromosome 4 for a concordant QTL related to milk protein traits in dairy cattle. Functional studies are needed to confirm this result. [ABSTRACT FROM AUTHOR]

The high growth (HG) mouse mutation is a 460 Kb deletion of chromosome 10 which causes a 30–50% increase in growth in the homozygous animal. We have shotgun sequenced six bacterial artificial chromosomes which span the length of the deletion to an average depth of 13.2× to generate a 649,868 bp sequence. Sequence analysis revealed the presence of three genes, suppressor of cytokine signaling-2 (Socs-2), caspase and RIP adaptor with death domain (Raidd/Cradd), and viral encoded semaphorin receptor (Plexin C1, viral encoded semaphorin receptor). The two deletion breakpoints lie in within the second introns of both Socs-2 and Plexin C1, resulting in the formation of a novel expressed fusion transcript between Socs-2 and Plexin C1 in HG mice. Expression of the fusion transcript, the presence of four splice variants of Raidd/Cradd and the exon structure of Socs-2 were illustrated using polymerase chain reaction. Genomic comparisons of the mouse and human sequence were used to verify the sequence assembly. [Copyright &y& Elsevier]

Background: Evidence exists that red wine, which contains a large array of polyphenols, is protective against cardiovascular disease and possibly cancer. Objective: We tested the hypothesis that catechin, the major monomeric polyphenol in red wine, can delay tumor onset in transgenic mice that spontaneously develop tumors. Design: Mice were fed a nutritionally complete amino acid-based diet supplemented with (+)-catechin (0-8 mmol/kg diet) or alcoholfree solids from red wine. Mice were examined daily; the age at which a first tumor appeared was recorded as the age at tumor onset. Plasma catechin and metabolite concentrations were quantified at the end of the study. Results: Dietary catechin significantly delayed tumor onset; a positive, linear relation was observed between the age at tumor onset and either the amount of dietary catechin (r2 = 0.761, P < 0.001) or plasma catechin and metabolite concentrations (r2 = 0.408, P = 0.003). No significant effects on tumor onset were observed when mice consumed a diet supplemented with wine solids containing < 0.22 mmol catechin/kg diet, whereas a previous study showed that wine solids with a similar total polyphenol concentration but containing ≈4 times more catechin significantly delayed tumor onset by ≈30 d compared with a control diet. The catechin composition of the wines is directly related to processing conditions during vinification. Conclusions: Physiologic intakes of specific dietary polyphenols, such as catechin, may play an important role in cancer chemoprevention. Wines have different polyphenol concentrations and compositions; therefore, the overall health benefits of individual wines differ. [ABSTRACT FROM AUTHOR]

The technological properties of milk have significant importance for the dairy industry. Citrate, a normal constituent of milk, forms one of the main buffer systems that regulate the equilibrium between Ca2+ and H+ ions. Higher-than-normal citrate content is associated with poor coagulation properties of milk. To identify the genes responsible for the variation of citrate content in milk in dairy cattle, the metabolic steps involved in citrate and fatty acid synthesis pathways in ruminant mammary tissue using RNA sequencing were studied. Genetic markers that could influence milk citrate content in Holstein cows were used in a marker-trait association study to establish the relationship between 74 single nucleotide polymorphisms (SNP) in 20 candidate genes and citrate content in 250 Holstein cows. This analysis revealed 6 SNP in key metabolic pathway genes [isocitrate dehydrogenase 1 (NADP+), soluble (IDH1); pyruvate dehydrogenase (lipoamide) β (PDHB); pyruvate kinase (PKM2); and solute carrier family 25 (mitochondrial carrier; citrate transporter), member 1 (SLC25A1)] significantly associated with increased milk citrate content. The amount of the phenotypic variation explained by the 6 SNP ranged from 10.1 to 13.7%. Also, genotype-combination analysis revealed the highest phenotypic variation was explained combining IDH1_23211, PDHB_5562, and SLC25A1_4446 genotypes. This specific genotype combination explained 21.3% of the phenotypic variation. The largest citrate associated effect was in the 3' untranslated region of the SLC25A1 gene, which is responsible for the transport of citrate across the mitochondrial inner membrane. This study provides an approach using RNA sequencing, metabolic pathway analysis, and association studies to identify genetic variation in functional target genes determining complex trait phenotypes. [ABSTRACT FROM AUTHOR]

Mastitis is a very costly and common disease in the dairy industry. The study of the transcriptome from healthy and mastitic milk somatic cell samples using RNA-Sequencing technology can provide measurements of transcript levels associated with the immune response to the infection. The objective of this study was to characterize the Holstein milk somatic cell transcriptome from 6 cows to determine host response to intramammary infections. RNA-Sequencing was performed on 2 samples from each cow from 2 separate quarters, one classified as healthy (n = 6) and one as mastitic (n = 6). In total, 449 genes were differentially expressed between the healthy and mastitic quarters (false discovery rate <0.05, fold change >±2). Among the differentially expressed genes, the most expressed genes based on reads per kilobase per million mapped reads (RPKM) in the healthy group were associated with milk components (CSN2 and CSN3), and in the mastitic group they were associated with immunity (B2M and CD74). In silico functional analysis was performed using the list of 449 differentially expressed genes, which identified 36 significantly enriched metabolic pathways (false discovery rate <0.01), some of which were associated with the immune system, such as cytokine-cytokine interaction and cell adhesion molecules. Seven functional candidate genes were selected, based on the criteria of being highly differentially expressed between healthy and mastitic groups and significantly enriched in metabolic pathways that are relevant to the inflammatory process (GLYCAM1 , B2M , CD74 , BoLA-DRA , FCER1G , SDS , and NFKBIA). Last, we identified the differentially expressed genes that are located in quantitative trait locus regions previously known to be associated with mastitis, specifically clinical mastitis, somatic cell count, and somatic cell score. It was concluded that multiple genes within quantitative trait locus regions could potentially affect host response to mastitis-causing agents, making some cows more susceptible to intramammary infections. The identification of potential candidate genes with functional, statistical, biological, and positional relevance associated with host defense to infection will contribute to a better understanding of the underlying genetic architecture associated with mastitis. This in turn will improve the sustainability of agricultural practices by facilitating the selection of cows with improved host defense leading to increased resistance to mastitis. [ABSTRACT FROM AUTHOR]

Calorie restriction (CR) consistently extends longevity and delays age-related diseases across several animal models. We have previously shown that different dietary fat sources can modulate life span and mitochondrial ultrastructure, function and membrane fatty acid composition in mice maintained on a 40% CR. In particular, animals consuming lard as the main fat source (CR-Lard) lived longer than CR mice consuming diets with soybean oil (CR-Soy) or fish oil (CR-Fish) as the predominant lipid source. In the present work, a transcriptomic analysis in the liver and skeletal muscle was performed in order to elucidate possible mechanisms underlying the changes in energy metabolism and longevity induced by dietary fat in CR mice. After 8 months of CR, transcription downstream of several mediators of inflammation was inhibited in liver. In contrast, proinflammatory signaling was increased in the CR-Fish versus other CR groups. Dietary fish oil induced a gene expression pattern consistent with increased transcriptional regulation by several cytokines (TNF, GM-CSF, TGF-β) and sex hormones when compared to the other CR groups. The CR-Fish also had lower expression of genes involved in fatty acid biosynthesis and increased expression of mitochondrial and peroxisomal fatty acid β-oxidation genes than the other CR diet groups. Our data suggest that a diet high in n-3 PUFA, partially reverts CR-related changes in gene expression of key processes, such as inflammation and steroid hormone signaling, and this may mitigate life span extension with CR in mice consuming diets high in fish oil. [ABSTRACT FROM AUTHOR]

A variety of proteases release hundreds of endogenous peptide fragments from intact bovine milk proteins. Mass spectrometry-based peptidomics allows for high throughput sequence assignment of a large number of these peptides. Mastitis is known to result in increased protease activity in the mammary gland. Therefore, we hypothesized that subclinically mastitic milks would contain higher concentrations of released peptides. In this work, milks were sampled from three cows and, for each, one healthy and one subclinically mastitic teat were sampled for milk. Peptides were analyzed by nano-liquid chromatography quadrupole time of flight tandem mass spectrometry and identified with database searching. In total, 682 peptides were identified. The total number of released peptides increased 146% from healthy to subclinically mastitic milks ( p < 0.05), and the total abundance of released peptides also increased significantly ( p < 0.05). Bioinformatic analysis of enzyme cleavage revealed increases in activity of cathepsin D and elastase ( p < 0.05) with subclinical mastitis. [ABSTRACT FROM AUTHOR]

Abstract: The genomic architecture and expression of the Igf-1 gene are complex yielding multiple IGF-I transcript isoforms with putative functional contributions to growth and metabolism. Using RNA-seq on different tissues, physiological states, and species, the breadth of transcripts expressed was determined. Tissues from pre- and post-pubertal heifers and mature mice were collected and the transcript isoforms characterized. Three different IGF-I isoforms were detected in heifers with Class 1 transcripts most abundantly expressed. The pituitary reduced IGF-I expression post-pubertally whereas the uterus increased expression. Murine IGF-I transcript expression was more diverse utilizing multiple exons, start sites, and 3′UTRs. The RNA-seq methodology to characterize expression profiles permits assessment of the transcript isoforms yielding insight into functional roles of each transcript. [Copyright &y& Elsevier]