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

Design of a single axis simulator for satellite control system testing and for low torque measurement

Single axis simulator design for satellite control system testing and low torque measuremen

Analysis of Accordion DNA Stretching Revealed by The Gold Cluster Ruler

A promising new method for measuring intramolecular distances in solution uses small-angle X-ray scattering interference between gold nanocrystal labels (Mathew-Fenn et al, Science, 322, 446 (2008)). When applied to double stranded DNA, it revealed that the DNA length fluctuations are strikingly strong and correlated over at least 80 base pair steps. In other words, the DNA behaves as accordion bellows, with distant fragments stretching and shrinking concertedly. This hypothesis, however, disagrees with earlier experimental and computational observations. This Letter shows that the discrepancy can be rationalized by taking into account the cluster exclusion volume and assuming a moderate long-range repulsion between them. The long-range interaction can originate from an ion exclusion effect and cluster polarization in close proximity to the DNA surface.Comment: 9 pages, 4 figures, to appear in Phys. Rev.

Measure Recognition Problem

This is an article in mathematics, specifically in set theory. On the example of the Measure Recognition Problem (MRP) the article highlights the phenomenon of the utility of a multidisciplinary mathematical approach to a single mathematical problem, in particular the value of a set-theoretic analysis. MRP asks if for a given Boolean algebra \algB and a property $\Phi$ of measures one can recognize by purely combinatorial means if \algB supports a strictly positive measure with property $\Phi$. The most famous instance of this problem is MRP(countable additivity), and in the first part of the article we survey the known results on this and some other problems. We show how these results naturally lead to asking about two other specific instances of the problem MRP, namely MRP(nonatomic) and MRP(separable). Then we show how our recent work D\v zamonja and Plebanek (2006) gives an easy solution to the former of these problems, and gives some partial information about the latter. The long term goal of this line of research is to obtain a structure theory of Boolean algebras that support a finitely additive strictly positive measure, along the lines of Maharam theorem which gives such a structure theorem for measure algebras

High power coupled CO2 waveguide laser array

A hollow-bore ridge waveguide technique for phase locking arrays of coupled CO2 rf excited waveguide lasers was demonstrated. Stable phase-locked operation of two- and three-channel arrays has been demonstrated at the 50 W output level. Preliminary experiments with a five-element array generated an output power of 95 W but phase-locked operation was not conclusively demonstrated