SNPs Meet CNVs in Genome-Wide Association Studies: HGV2007 Meeting Report

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SNPs Meet CNVs in Genome-Wide Association Studies: HGV2007 Meeting Report

SNPs meet CNVs in genome-wide association studies: HGV2007 meeting repor

Identification of Reissner's fiber-like glycoproteins in two species of freshwater planarians (Tricladida), by use of specific polyclonal and monoclonal antibodies

By using one polyclonal antiserum raised against bovine Reissner's fiber and seven monoclonal antibodies raised against bovine Reissner's fiber and against immunopurified bovine subcommissural organ glycoproteins, we have investigated two freshwater planarian species (Girardia tigrina, Schmidtea mediterranea) by light- and electron-microscopic immunocytochemistry. ELISA probes showed that the monoclonal antibodies recognized different, nonoverlapping, unrepeated, proteinaceous epitopes present in the same compounds of bovine Reissner's fiber. Cells immunoreactive to the polyclonal and monoclonal antibodies were found in the dorsal and ventral integument of both planarian species. Labeled cuboid epidermal cells bore cilia and displayed several types of secretory granules; they were covered by a film of immunoreactive material. Studies on adjacent thin and semithin sections revealed coexistence of label in the same regions and in the same cells when two different monoclonal antibodies were used. These results indicate that a secretory substance immunologically similar to the secretion of the vertebrate subcommissural organ is present in primitive tripoblasts such as planarians, suggesting that these secretions are ancient and well conserved in phylogeny

Quantification of the secretory glycoproteins of the subcommissural organ by a sensitive sandwich ELISA with a polyclonal antibody and a set of monoclonal antibodies against the bovine Reissner's fiber

The subcommissural organ (SCO) is an ependymal brain gland that releases glycoproteins into the ventricular cerebrospinal fluid where they condense to form the Reissner's fiber (RF). We have developed a highly sensitive and specific two-antibody sandwich enzyme-linked immunosorbent assay (ELISA) for the quantification of the bovine SCO secretory material. The assay was based on the use of the IgG fraction of a polyclonal antiserum against the bovine RF as capture antibody and a pool of three peroxidase-labeled monoclonal antibodies that recognize non-overlapping epitopes of the RF glycoproteins as detection antibody. The detection limit was 1 ng/ml and the working range extended from 1 to 4000 ng/ml. The calibration curve, generated with RF glycoproteins, showed two linear segments: one of low sensitivity, ranging from 1 to 125 ng/ml, and the other of high sensitivity between 125 and 4000 ng/ml. This assay was highly reproducible (mean intra- and interassay coefficient of variation 2.2% and 5.3%, respectively) and its detectability and sensitivity were higher than those of ELISAs using exclusively either polyclonal or monoclonal antibodies against RF glycoproteins. The assay succeeded in detecting and measuring secretory material in crude extracts of bovine SCO, culture medium supernatant of SCO explants and incubation medium of bovine RF; however, soluble secretory material was not detected in bovine cerebrospinal fluid

Eina gràfica per la creació d'autòmats per a la representació del llenguatge natural

Aquest projecte tracta la implementació d'una eina gràfica multiplataforma de creació i edició de gramàtiques electròniques per representar el Llenguatge Natural. És una eina per lingüistes i projectes com Spanish FrameNet Project amb la quan poden representar fàcilment transductors en un format més visual, les transicions es representen en forma de "caixes", i guardar els resultats. S'han implementat varies opcions per crear una eina còmode i personalitzable per l'usuari amb funcionalitats enfocades a les seves necessitats com importar/exportar autòmats des d'una Expressió Regular. Es tracta l'implementació de tots els components que s'han necessitat per crear la GUI així com la seva funcionalitat.Este proyecto trata la implementación de una herramienta gráfica multiplataforma de creación y edición de gramáticas electrónicas para representar el Lenguaje Natural. Es una herramienta para lingüistas y proyectos como Spanish FrameNet Project con la cual puedan representar fácilmente transductores en un formato visual, las transiciones se representan en forma de "cajas", y guardar el resultado. Se han implementado varias opciones para crear una herramienta cómoda y personalizable para el usuario con funcionalidades destinadas a sus necesidades como importar/exportar autómatas desde una Expresión Regular. Se trata de la implementación de todos los componentes que han sido necesarios para la GUI así como su funcionalidad.This project is implementing a multi-platform graphical tool for creating and editing electronic grammars to represent the natural language. Linguists and projects such as Spanish FrameNet Project could use this tool to easily represent transducers in a visual format, where transitions are represented with a "box" shape, and save the results. Several options have been implemented to create a comfortable and customizable tool for the user with functionality for his needs as import/export from a Regular Expression. This is the implementation of all components that have been necessary for the GUI and functionally

Vertex Cover Kernelization Revisited: Upper and Lower Bounds for a Refined Parameter

An important result in the study of polynomial-time preprocessing shows that there is an algorithm which given an instance (G,k) of Vertex Cover outputs an equivalent instance (G',k') in polynomial time with the guarantee that G' has at most 2k' vertices (and thus O((k')^2) edges) with k' <= k. Using the terminology of parameterized complexity we say that k-Vertex Cover has a kernel with 2k vertices. There is complexity-theoretic evidence that both 2k vertices and Theta(k^2) edges are optimal for the kernel size. In this paper we consider the Vertex Cover problem with a different parameter, the size fvs(G) of a minimum feedback vertex set for G. This refined parameter is structurally smaller than the parameter k associated to the vertex covering number vc(G) since fvs(G) <= vc(G) and the difference can be arbitrarily large. We give a kernel for Vertex Cover with a number of vertices that is cubic in fvs(G): an instance (G,X,k) of Vertex Cover, where X is a feedback vertex set for G, can be transformed in polynomial time into an equivalent instance (G',X',k') such that |V(G')| <= 2k and |V(G')| <= O(|X'|^3). A similar result holds when the feedback vertex set X is not given along with the input. In sharp contrast we show that the Weighted Vertex Cover problem does not have a polynomial kernel when parameterized by the cardinality of a given vertex cover of the graph unless NP is in coNP/poly and the polynomial hierarchy collapses to the third level.Comment: Published in "Theory of Computing Systems" as an Open Access publicatio

BETULA: Numerically Stable CF-Trees for BIRCH Clustering

BIRCH clustering is a widely known approach for clustering, that has influenced much subsequent research and commercial products. The key contribution of BIRCH is the Clustering Feature tree (CF-Tree), which is a compressed representation of the input data. As new data arrives, the tree is eventually rebuilt to increase the compression. Afterward, the leaves of the tree are used for clustering. Because of the data compression, this method is very scalable. The idea has been adopted for example for k-means, data stream, and density-based clustering. Clustering features used by BIRCH are simple summary statistics that can easily be updated with new data: the number of points, the linear sums, and the sum of squared values. Unfortunately, how the sum of squares is then used in BIRCH is prone to catastrophic cancellation. We introduce a replacement cluster feature that does not have this numeric problem, that is not much more expensive to maintain, and which makes many computations simpler and hence more efficient. These cluster features can also easily be used in other work derived from BIRCH, such as algorithms for streaming data. In the experiments, we demonstrate the numerical problem and compare the performance of the original algorithm compared to the improved cluster features

Association of neurexin 3 polymorphisms with smoking behavior.

The Neurexin 3 gene (NRXN3) has been associated with dependence on various addictive substances, as well as with the degree of smoking in schizophrenic patients and impulsivity among tobacco abusers. To further evaluate the role of NRXN3 in nicotine addiction, we analyzed single nucleotide polymorphisms (SNPs) and a copy number variant (CNV) within the NRXN3 genomic region. An initial study was carried out on 157 smokers and 595 controls, all of Spanish Caucasian origin. Nicotine dependence was assessed using the Fagerstrom index and the number of cigarettes smoked per day. The 45 NRXN3 SNPs genotyped included all the SNPs previously associated with disease, and a previously described deletion within NRXN3. This analysis was replicated in 276 additional independent smokers and 568 controls. Case-control association analyses were performed at the allele, genotype and haplotype levels. Allelic and genotypic association tests showed that three NRXN3 SNPs were associated with a lower risk of being a smoker. The haplotype analysis showed that one block of 16 Kb, consisting of two of the significant SNPs (rs221473 and rs221497), was also associated with lower risk of being a smoker in both the discovery and the replication cohorts, reaching a higher level of significance when the whole sample was considered [odds ratio = 0.57 (0.42-0.77), permuted P = 0.0075]. By contrast, the NRXN3 CNV was not associated with smoking behavior. Taken together, our results confirm a role for NRXN3 in susceptibility to smoking behavior, and strongly implicate this gene in genetic vulnerability to addictive behaviors

On the Recognition of Four-Directional Orthogonal Ray Graphs

Orthogonal ray graphs are the intersection graphs of horizontal and vertical rays (i.e. half-lines) in the plane. If the rays can have any possible orientation (left/right/up/down) then the graph is a 4-directional orthogonal ray graph (4-DORG). Otherwise, if all rays are only pointing into the positive x and y directions, the intersection graph is a 2-DORG. Similarly, for 3-DORGs, the horizontal rays can have any direction but the vertical ones can only have the positive direction. The recognition problem of 2-DORGs, which are a nice subclass of bipartite comparability graphs, is known to be polynomial, while the recognition problems for 3-DORGs and 4-DORGs are open. Recently it has been shown that the recognition of unit grid intersection graphs, a superclass of 4-DORGs, is NP-complete. In this paper we prove that the recognition problem of 4-DORGs is polynomial, given a partition {L,R,U,D} of the vertices of G (which corresponds to the four possible ray directions). For the proof, given the graph G, we first construct two cliques G 1,G 2 with both directed and undirected edges. Then we successively augment these two graphs, constructing eventually a graph TeX with both directed and undirected edges, such that G has a 4-DORG representation if and only if TeX has a transitive orientation respecting its directed edges. As a crucial tool for our analysis we introduce the notion of an S-orientation of a graph, which extends the notion of a transitive orientation. We expect that our proof ideas will be useful also in other situations. Using an independent approach we show that, given a permutation π of the vertices of U (π is the order of y-coordinates of ray endpoints for U), while the partition {L,R} of V ∖ U is not given, we can still efficiently check whether G has a 3-DORG representation

Fat Mass and Obesity-Associated Gene (FTO) in Eating Disorders: Evidence for Association of the rs9939609 Obesity Risk Allele with Bulimia nervosa and Anorexia nervosa

Objective: The common single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity-associated gene (FTO) is associated with obesity. As genetic variants associated with weight regulation might also be implicated in the etiology of eating disorders, we evaluated whether SNP rs9939609 is associated with bulimia nervosa (BN) and anorexia nervosa (AN). Methods: Association of rs9939609 with BN and AN was assessed in 689 patients with AN, 477 patients with BN, 984 healthy non-population-based controls, and 3,951 population-based controls (KORA-S4). Based on the familial and premorbid occurrence of obesity in patients with BN, we hypothesized an association of the obesity risk A-allele with BN. Results: In accordance with our hypothesis, we observed evidence for association of the rs9939609 A-allele with BN when compared to the non-population-based controls (unadjusted odds ratio (OR) = 1.142, one-sided 95% confidence interval (CI) 1.001-infinity; one-sided p = 0.049) and a trend in the population-based controls (OR = 1.124, one-sided 95% CI 0.932-infinity; one-sided p = 0.056). Interestingly, compared to both control groups, we further detected a nominal association of the rs9939609 A-allele to AN (OR = 1.181, 95% CI 1.027-1.359, two-sided p = 0.020 or OR = 1.673, 95% CI 1.101-2.541, two-sided p = 0.015,). Conclusion: Our data suggest that the obesity-predisposing FTO allele might be relevant in both AN and BN. Copyright (C) 2012 S. Karger GmbH, Freibur