Biological networks and epistasis in genome-wide association studies

Over the last few years, technological improvements have made possible the genotyping of hundreds of thousands of SNPs, enabling whole-genome association studies. The first genome-wide association studies have recently been completed to detect causal variant for complex traits. Although increasing evidence suggests that interaction between loci, such as epistasis between two loci, should be considered, most of these studies proceed by considering each SNP independently. One reason for this choice is that looking at all pairs of SNPs increases dramatically the number of tests (approximatively 50 billions of tests for a 300,000 SNPs data set) that faces with computational limitation and strong multiple testing correction.
We proposed to reduce the number of tests by focusing on pairs of SNPs that belong to genes known to interact in some metabolic network. Although some interactions might be missed, these pairs of genes are good candidates for epistasis. Furthermore the use of protein interaction databases (such as the STRING database) may reduce the number of tests by a factor of 5,000.
Results using this approach will be presented on simulated data sets and on public data sets.
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A Computational Pipeline for the Development of Comparative Anchor Tagged Sequence (CATS) Markers

Key points: Molecular markers that allow the transfer of map information from one species to another are vital in comparative genetics. To identify potential anchor marker sequences more efficiently, we have established a bioinformatic pipeline that combines multi-species EST- and genome- sequence data. Taking advantage of information from a few related species, comparative EST sequence analysis identifies evolutionary conserved sequences in less well-characterised species in the same family. Alignment of evolutionary conserved EST sequences with corresponding genomic sequences defines sets of PCR primer sites flanking introns. Markers identified by this procedure will be readily transferable to other species since they are selected on the basis of their common evolutionary origin. We exemplify our procedure on legumes and grasses, where model plant studies and the genome- and EST-sequence data available have a potential impact on breeding crop species

Application of a pig ligated intestinal loop model for early Lawsonia intracellularis infection

<p>Abstract</p> <p>Background</p> <p>Porcine proliferative enteropathy in pigs is caused by the obligate, intracellular bacterium <it>Lawsonia intracellularis</it>. <it>In vitro </it>studies have shown close bacterium-cell interaction followed by cellular uptake of the bacterium within 3 h post inoculation (PI). However, knowledge of the initial <it>in vivo </it>interaction between porcine intestinal epithelium and the bacterium is limited. The aims of the present study were to evaluate the usefulness of a ligated small intestinal loop model to study <it>L. intracellularis </it>infections and to obtain information on the very early <it>L. intracellularis</it>-enterocyte interactions.</p> <p>Methods</p> <p>A ligated small intestinal loop model using three different <it>L. intracellularis </it>inocula was applied to 10-11-week-old pigs. The inocula were 1) wild type bacteria derived from overnight incubation of <it>L. intracellularis </it>bacteria from spontaneous disease, 2) crude vaccine bacteria (Enterisol^®Ileitis Vet), and 3) vaccine bacteria propagated in cell culture. The bacteria-enterocyte interaction was visualised using immunohistochemistry on specimens derived 1, 3 and 6 h PI respectively.</p> <p>Results</p> <p>Although at a low level, close contact between bacteria and the enterocyte brush border including intracellular uptake of bacteria in mature enterocytes was seen at 3 and 6 h PI for the vaccine and the propagated vaccine inocula. Interaction between the wild-type bacteria and villus enterocytes was scarce and only seen at 6 h PI, where a few bacteria were found in close contact with the brush border.</p> <p>Conclusions</p> <p>The ligated intestinal loop model was useful with respect to maintaining an intact intestinal morphology for up to 6 h. Furthermore, the study demonstrated that <it>L. intracellularis </it>interacts with villus enterocytes within 3 to 6 h after inoculation into intestinal loops and that the bacterium, as shown for the vaccine bacteria, propagated as well as non-propagated, was able to invade mature enterocytes. Thus, the study demonstrates the early intestinal invasion of <it>L. intracellularis in vivo</it>.</p

Lithium Dendrite Growth in Glassy and Rubbery Nanostructured Block Copolymer Electrolytes

Enabling the use of lithium metal anodes is a critical step required to dramatically increase the energy density of rechargeable batteries. However, dendrite growth in lithium metal batteries, and a lack of fundamental understanding of the factors governing this growth, is a limiting factor preventing their adoption. Herein we present the effect of battery cycling temperature, ranging from 90 to 120°C, on dendrite growth through a polystyrene-block-poly(ethylene oxide)-based electrolyte. This temperature range encompasses the glass transition temperature of polystyrene (107°C). A slight increase in the cycling temperature of symmetric lithium-polymer-lithium cells from 90 to 105°C results in a factor of five decrease in the amount of charge that can be passed before short circuit. Synchrotron hard X-ray microtomography experiments reveal a shift in dendrite location from primarily within the lithium electrode at 90°C, to primarily within the electrolyte at 105°C. Rheological measurements show a large change in mechanical properties over this temperature window. Time-temperature superposition was used to interpret the rheological data. Dendrite growth characteristics and cell lifetimes correlate with the temperature-dependent shift factors used for time-temperature superposition. Our work represents a step toward understanding the factors that govern lithium dendrite growth in viscoelastic electrolytes

GeMprospector—online design of cross-species genetic marker candidates in legumes and grasses

The web program GeMprospector (URL: ) allows users to automatically design large sets of cross-species genetic marker candidates targeting either legumes or grasses. The user uploads a collection of ESTs from one or more legume or grass species, and they are compared with a database of clusters of homologous EST and genomic sequences from other legumes or grasses, respectively. Multiple sequence alignments between submitted ESTs and their homologues in the appropriate database form the basis of automated PCR primer design in conserved exons such that each primer set amplifies an intron. The only user input is a collection of ESTs, not necessarily from more than one species, and GeMprospector can boost the potential of such an EST collection by combining it with a large database to produce cross-species genetic marker candidates for legumes or grasses

CoaSim: A flexible environment for simulating genetic data under coalescent models

BACKGROUND: Coalescent simulations are playing a large role in interpreting large scale intra-specific sequence or polymorphism surveys and for planning and evaluating association studies. Coalescent simulations of data sets under different models can be compared to the actual data to test the importance of different evolutionary factors and thus get insight into these. RESULTS: We have created the CoaSim application as a flexible environment for Monte Carlo simulation of various types of genetic data under equilibrium and non-equilibrium coalescent processes for a variety of applications. Interaction with the tool is through the Guile version of the Scheme scripting language. Scheme scripts for many standard and advanced applications are provided and these can easily be modified by the user for a much wider range of applications. A graphical user interface with less functionality and flexibility is also included. It is primarily intended as an exploratory and educational tool CONCLUSION: CoaSim is a powerful tool because of its flexibility and ease of use. This is illustrated through very varied uses of the application, e.g. evaluation of association mapping methods, parametric bootstrapping, and design and choice of markers for specific question

Can legume systeny be useful in guiding the introgression of wild genes into cultivated peanut?

Edição dos resumos do Workshop, Porto Alegre, RS, 2007

Can legume synteny be useful in guiding the introgression of wild genes into cultivated peanut?

Edição do International Workshop Integrating Genomics Into Plant Breeding, Porto Alegre, out. 2007