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

Bibliographic lnstruction - Credit Courses

Barbara Wittkopf, in a summary of her survey of ARL Libraries ["A Look at the State of BI Credit Courses in ARL-Member Libraries." Research Strategies 9 (Fall 199 1): 162- 1631 states that "there has been a positive shift away from library orientation tours and tool-specific instruction toward the development of research skills and strategies." Some academic libraries have offered a credit course in library research skills for years, while others have recently added a course to cope with the need for information literacy education. In addition to decisions about what and how to teach, the procedures for offering such a credit course vary greatly from institution to institution

Feeding ecology of juvenile Pacific salmon (Oncorhynchus spp.) in a northeast Pacific fjord: diet, availability of zooplankton, selectivity for prey, and potential competition for prey resources

We investigated the feeding ecology of juvenile salmon during the critical early life-history stage of transition from shallow to deep marine waters by sampling two stations (190 m and 60 m deep) in a northeast Pacific fjord (Dabob Bay, WA) between May 1985 and October 1987. Four species of Pacific salmon—Oncorhynchus keta (chum) , O. tshawytscha (Chinook), O. gorbuscha (pink), and O. kisutch (coho)—were examined for stomach contents. Diets of these fishes varied temporally, spatially, and between species, but were dominated by insects, euphausiids, and decapod larvae. Zooplankton assemblages and dry weights differed between stations, and less so between years. Salmon often demonstrated strongly positive or negative selection for specific prey types: copepods were far more abundant in the zooplankton than in the diet, whereas Insecta, Araneae, Cephalapoda, Teleostei, and Ctenophora were more abundant in the diet than in the plankton. Overall diet overlap was highest for Chinook and coho salmon (mean=77.9%)—species that seldom were found together. Chum and Chinook salmon were found together the most frequently, but diet overlap was lower (38.8%) and zooplankton biomass was not correlated with their gut fullness (%body weight). Thus, despite occasional occurrences of significant diet overlap between salmon species, our results indicate that interspecific competition among juvenile salmon does not occur in Dabob Bay

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

Outdoor Recreation Constraints: An Examination of Race, Gender, and Rural Dwelling

We assess whether traditionally marginalized groups in American society (African-Americans, women, rural dwellers) perceive more constraints to outdoor recreation participation than other groups. A series of logistic regressions are applied to a national recreation survey and used to model the probability that individuals perceive certain constraints to participating in outdoor recreation activities. Twelve constraints related to health, facilities, socioeconomic standing, and other personal factors are examined for both participants and nonparticipants of outdoor recreation. We model the probability that individuals report being constrained in participating in their favorite activities as a function of race, gender, and rural residence. In addition, we control for income, age, regional differences, and activity groupings. Of the three groups examined, women are most likely to feel constrained--for instance, by personal safety concerns, inadequate facilities and information, insufficient funds, and outdoor pests. Race is not a significant predictor of constraints for participants, but nonparticipating African-Americans are more likely than whites to feel personal safety concerns inhibit their outdoor recreation opportunities. Rural residence does not appear to be an important factor among either participants or nonparticipants in explaining the probability that an individual feels constrained in outdoor recreation participation

Urban water demand forecasting and demand management: Research needs review and recommendations

Urban Water Demand Forecasting and Demand Management - Research Needs Review and Recommendations This study undertook a preliminary investigation of current research into urban water demand. The objective was to conduct a preliminary review of this field, to provide the beginnings of a comprehensive database of industry knowledge in this area and to identify research gaps. It is anticipated that this will lead to a more considered approach to research funding by the Australian water industry and maximise the potential for transparency and collaboratio

Anxiety in Williams Syndrome: The role of social behaviour, executive functions and change over time

Anxiety is a prevalent mental health issue for individuals with Williams syndrome (WS). Relatively little is known about the developmental course of anxiety, or how it links with core features of WS, namely social and executive functioning (EF). In this study, parent-reports of anxiety were compared across a 4-year period (N = 17), and links between anxiety, social and EF were explored from concurrent parent-reports (N = 26). Results indicated that high anxiety persisted over time, and anxiety was related to impairments in both social and executive functioning. Importantly, results indicated that impairments in EFs may drive the links between anxiety and social functioning. This timely investigation provides new insights into anxiety in WS and highlights potential areas for intervention