A genome-wide SNP-association study confirms a sequence variant (g.66493737C>T) in the equine myostatin (MSTN) gene as the most powerful predictor of optimum racing distance for Thoroughbred racehorses

<p>Abstract</p> <p>Background</p> <p>Thoroughbred horses have been selected for traits contributing to speed and stamina for centuries. It is widely recognized that inherited variation in physical and physiological characteristics is responsible for variation in individual aptitude for race distance, and that muscle phenotypes in particular are important.</p> <p>Results</p> <p>A genome-wide SNP-association study for optimum racing distance was performed using the EquineSNP50 Bead Chip genotyping array in a cohort of <it>n </it>= 118 elite Thoroughbred racehorses divergent for race distance aptitude. In a cohort-based association test we evaluated genotypic variation at 40,977 SNPs between horses suited to short distance (≤ 8 f) and middle-long distance (> 8 f) races. The most significant SNP was located on chromosome 18: BIEC2-417495 ~690 kb from the gene encoding myostatin (<it>MSTN</it>) [<it>P</it>_unadj.= 6.96 × 10^-6]. Considering best race distance as a quantitative phenotype, a peak of association on chromosome 18 (chr18:65809482-67545806) comprising eight SNPs encompassing a 1.7 Mb region was observed. Again, similar to the cohort-based analysis, the most significant SNP was BIEC2-417495 (<it>P</it>_unadj.= 1.61 × 10^-9; <it>P</it>_Bonf.= 6.58 × 10^-5). In a candidate gene study we have previously reported a SNP (g.66493737C>T) in <it>MSTN </it>associated with best race distance in Thoroughbreds; however, its functional and genome-wide relevance were uncertain. Additional re-sequencing in the flanking regions of the <it>MSTN </it>gene revealed four novel 3' UTR SNPs and a 227 bp SINE insertion polymorphism in the 5' UTR promoter sequence. Linkage disequilibrium was highest between g.66493737C>T and BIEC2-417495 (<it>r</it>²= 0.86).</p> <p>Conclusions</p> <p>Comparative association tests consistently demonstrated the g.66493737C>T SNP as the superior variant in the prediction of distance aptitude in racehorses (g.66493737C>T, <it>P </it>= 1.02 × 10^-10; BIEC2-417495, <it>P</it>_unadj.= 1.61 × 10^-9). Functional investigations will be required to determine whether this polymorphism affects putative transcription-factor binding and gives rise to variation in gene and protein expression. Nonetheless, this study demonstrates that the g.66493737C>T SNP provides the most powerful genetic marker for prediction of race distance aptitude in Thoroughbreds.</p

A gene expression atlas of the domestic pig

<p>Abstract</p> <p>Background</p> <p>This work describes the first genome-wide analysis of the transcriptional landscape of the pig. A new porcine Affymetrix expression array was designed in order to provide comprehensive coverage of the known pig transcriptome. The new array was used to generate a genome-wide expression atlas of pig tissues derived from 62 tissue/cell types. These data were subjected to network correlation analysis and clustering.</p> <p>Results</p> <p>The analysis presented here provides a detailed functional clustering of the pig transcriptome where transcripts are grouped according to their expression pattern, so one can infer the function of an uncharacterized gene from the company it keeps and the locations in which it is expressed. We describe the overall transcriptional signatures present in the tissue atlas, where possible assigning those signatures to specific cell populations or pathways. In particular, we discuss the expression signatures associated with the gastrointestinal tract, an organ that was sampled at 15 sites along its length and whose biology in the pig is similar to human. We identify sets of genes that define specialized cellular compartments and region-specific digestive functions. Finally, we performed a network analysis of the transcription factors expressed in the gastrointestinal tract and demonstrate how they sub-divide into functional groups that may control cellular gastrointestinal development.</p> <p>Conclusions</p> <p>As an important livestock animal with a physiology that is more similar than mouse to man, we provide a major new resource for understanding gene expression with respect to the known physiology of mammalian tissues and cells. The data and analyses are available on the websites <url>http://biogps.org and http://www.macrophages.com/pig-atlas</url>.</p

HExDB: a database for epigenetic changes occurring after horse exercise

DNA methylation is an essential biochemical modification that regulates gene expression. Exercise induces changes in gene expression that adapt as metabolic changes in the blood. We provide a database for the epigenetic changes after horse exercise . Horse Exercise Epigenetic Database (HExDB) explicates the change in genome-wide DNA methylation patterns after exercise. Exercise changes the genome-wide epigenetic patterns, and understanding the regions that change is important for confirming exercise physiological mechanisms. For this purpose, our database provides information on differentially methylated regions after exercise that pass a set threshold. A total of 784 genes based on NCBI RefSeq were identified as differentially methylated in equines after exercise. Our database provides clues for the study of exercise-related epigenetic pathways in the thoroughbred horseclose0

Exploring successful community pharmacist-physician collaborative working relationships using mixed methods

Background: Collaborative working relationships (CWRs) between community pharmacists and physicians may foster the provision of medication therapy management services, disease state management, and other patient care activities; however, pharmacists have expressed difficulty in developing such relationships. Additional work is needed to understand the specific pharmacist-physician exchanges that effectively contribute to the development of CWR. Data from successful pairs of community pharmacists and physicians may provide further insights into these exchange variables and expand research on models of professional collaboration. Objective: To describe the professional exchanges that occurred between community pharmacists and physicians engaged in successful CWRs, using a published conceptual model and tool for quantifying the extent of collaboration. Methods: A national pool of experts in community pharmacy practice identified community pharmacists engaged in CWRs with physicians. Five pairs of community pharmacists and physician colleagues participated in individual semistructured interviews, and 4 of these pairs completed the Pharmacist-Physician Collaborative Index (PPCI). Main outcome measures include quantitative (ie, scores on the PPCI) and qualitative information about professional exchanges within 3 domains found previously to influence relationship development: relationship initiation, trustworthiness, and role specification. Results: On the PPCI, participants scored similarly on trustworthiness; however, physicians scored higher on relationship initiation and role specification. The qualitative interviews revealed that when initiating relationships, it was important for many pharmacists to establish open communication through face-to-face visits with physicians. Furthermore, physicians were able to recognize in these pharmacists a commitment for improved patient care. Trustworthiness was established by pharmacists making consistent contributions to care that improved patient outcomes over time. Open discussions regarding professional roles and an acknowledgment of professional norms (ie, physicians as decision makers) were essential. Conclusions: The findings support and extend the literature on pharmacist-physician CWRs by examining the exchange domains of relationship initiation, trustworthiness, and role specification qualitatively and quantitatively among pairs of practitioners. Relationships appeared to develop in a manner consistent with a published model for CWRs, including the pharmacist as relationship initiator, the importance of communication during early stages of the relationship, and an emphasis on high-quality pharmacist contributions. © 2010 Elsevier Inc