Gene expression in large pedigrees: analytic approaches.

BackgroundWe currently have the ability to quantify transcript abundance of messenger RNA (mRNA), genome-wide, using microarray technologies. Analyzing genotype, phenotype and expression data from 20 pedigrees, the members of our Genetic Analysis Workshop (GAW) 19 gene expression group published 9 papers, tackling some timely and important problems and questions. To study the complexity and interrelationships of genetics and gene expression, we used established statistical tools, developed newer statistical tools, and developed and applied extensions to these tools.MethodsTo study gene expression correlations in the pedigree members (without incorporating genotype or trait data into the analysis), 2 papers used principal components analysis, weighted gene coexpression network analysis, meta-analyses, gene enrichment analyses, and linear mixed models. To explore the relationship between genetics and gene expression, 2 papers studied expression quantitative trait locus allelic heterogeneity through conditional association analyses, and epistasis through interaction analyses. A third paper assessed the feasibility of applying allele-specific binding to filter potential regulatory single-nucleotide polymorphisms (SNPs). Analytic approaches included linear mixed models based on measured genotypes in pedigrees, permutation tests, and covariance kernels. To incorporate both genotype and phenotype data with gene expression, 4 groups employed linear mixed models, nonparametric weighted U statistics, structural equation modeling, Bayesian unified frameworks, and multiple regression.Results and discussionRegarding the analysis of pedigree data, we found that gene expression is familial, indicating that at least 1 factor for pedigree membership or multiple factors for the degree of relationship should be included in analyses, and we developed a method to adjust for familiality prior to conducting weighted co-expression gene network analysis. For SNP association and conditional analyses, we found FaST-LMM (Factored Spectrally Transformed Linear Mixed Model) and SOLAR-MGA (Sequential Oligogenic Linkage Analysis Routines -Major Gene Analysis) have similar type 1 and type 2 errors and can be used almost interchangeably. To improve the power and precision of association tests, prior knowledge of DNase-I hypersensitivity sites or other relevant biological annotations can be incorporated into the analyses. On a biological level, eQTL (expression quantitative trait loci) are genetically complex, exhibiting both allelic heterogeneity and epistasis. Including both genotype and phenotype data together with measurements of gene expression was found to be generally advantageous in terms of generating improved levels of significance and in providing more interpretable biological models.ConclusionsPedigrees can be used to conduct analyses of and enhance gene expression studies

Mass Media Gatekeepers for Colleges of Agriculture

To reach the public, most news and information from colleges of agriculture must pass through an intermediary. This man in the middle is called a mass media gatekeeper. He literally has the power to open or close the gate to any material he gets from colleges of agriculture

Youth Sport Concussion Management

As knowledge about concussions increases and more is being discovered regarding the lasting effects of concussions, youth sport coaches need to be better informed and educated on the signs and symptoms, the management of concussions, and return-to-play procedures. This research examines what coaches of youth athletes (5-14 years of age) know about concussions and concussion management. Semi-structured interviews with coaches were conducted and analyzed in order to develop recommendations for effective training tools to help coaches identify and properly manage youth sport concussions. Results from the interviews found that coaches need more training on the long-term symptoms of concussions. The training should also include proper concussion management steps to take because coaches seemed to miss a few key steps in the management process. The results also indicated that a training should be required for parents and players

An EMG and Video Analysis of the Wrist Flexors during a Sidearm Baseball Delivery

By understanding proper pitching mechanics, therapists can develop better preventative and rehabilitation programs for pitchers. The purpose of this study was to explain the joint motions and muscle activity that occur at the elbow during both an overhand and sidearm baseball pitching delivery. Three healthy adult pitchers with recreational sidearm pitching experience were examined with synchronized high-speed video digitization and surface electromyography (EMG). It was proposed that the increased valgus moment during the acceleration phase due to the sidearm delivery would subsequently show an increase in EMG activity by the wrist flexor-pronator group to provide additional varus torque in minimizing the generated valgus moment. Results of the study did not indicate an increase in muscle activity of the wrist flexor-pronator group during the acceleration phase of the sidearm throws. However, subject #3 showed altered mechanics during the sidearm throw, and the peak muscle activity was displayed during the cocking phase rather than the deceleration phase. All other throws examined, both overhand and sidearm, resulted in peak muscle activity in the deceleration phase. Tradition based knowledge passed from one generation to the next speaks of the harmful effects at the elbow with throwing sidearm. However, this study did not support tradition based knowledge, and it showed minimal if any muscle activation patterns which differ from previous literature

Analysis of North American Rheumatoid Arthritis Consortium data using a penalized logistic regression approach

We applied a penalized regression approach to single-nucleotide polymorphisms in regions on chromosomes 1, 6, and 9 of the North American Rheumatoid Arthritis Consortium data. Results were compared with a standard single-locus association test. Overall, the penalized regression approach did not appear to offer any advantage with respect to either detection or localization of disease-associated polymorphisms, compared with the single-locus approach

Neglecting polydispersity degrades propensity measurements in supercooled liquids

We conduct molecular dynamics simulations of a bidisperse Kob-Andersen (KA) glass former, modified to add in additional polydispersity. The original KA system is known to exhibit dynamical heterogeneity. Prior work defined propensity, the mean motion of a particle averaged over simulations reconstructing the initial positions of all particles but with randomized velocities. The existence of propensity shows that structure and dynamics are connected. In this paper, we study systems which mimic problems that would be encountered in measuring propensity in a colloidal glass former, where particles are polydisperse (they have slight size variations). We mimic polydispersity by altering the bidisperse KA system into a quartet consisting of particles both slightly larger and slightly smaller than the parent particles in the original bidisperse system. We then introduce errors into the reconstruction of the initial positions that mimic mistakes one might make in a colloidal experiment. The mistakes degrade the propensity measurement, in some cases nearly completely; one no longer has an isoconfigurational ensemble in any useful sense. Our results show that a polydisperse sample is suitable for propensity measurements provided one avoids reconstruction mistakes.Comment: Implications for hypothetical colloidal experiment to test propensit

THE USE OF PRIVATE LANDS IN THE U.S. FOR OUTDOOR RECREATION: RESULTS OF A NATIONWIDE SURVEY

Land Economics/Use, Resource /Energy Economics and Policy,

Linkage and association analysis of GAW15 simulated data: fine-mapping of chromosome 6 region

We performed linkage and family-based association analysis across chromosomes 1–22 in Replicates 1–5 of the Genetic Analysis Workshop 15 simulated data. Linkage analysis was performed using the Kong and Cox allele-sharing test as implemented in the program Merlin. Association analysis was performed using the transmission/disequilibrium test (TDT). A region on chromosome 6 was consistently highlighted as showing significant linkage to and association with the disease trait. We focused in on this region and performed fine-mapping using stepwise regression approaches using the case/control and family-based data. In this region, we also applied several new methods, implemented in the computer programs LAMP and Graphminer, respectively, that have recently been proposed for association analysis with family and/or case/control data. All methods confirmed the highly significant associations previously observed. Differentiating between potentially causal single nucleotide polymorphisms (SNPs) and other non-causal loci (associated with disease merely due to linkage disequilibrium) proved to be problematic. However, in most replicates we did identify two SNPs (either SNPs 3437 and 3439 from the dense SNP set, or SNPs 153 and 3437 from the combined non-dense/dense SNP set) that together explain most of the observed disease association in the DR/C locus region, and an additional SNP (3931 or 3933) that accounts for the association 5 cM away at locus D