Characterization and evolution of the novel gene family FAM90A in primates originated by multiple duplication and rearrangement events

Genomic plasticity of human chromosome 8p23.1 region is highly influenced by two groups of complex segmental duplications (SDs), termed REPD and REPP, that mediate different kinds of rearrangements. Part of the difficulty to explain the wide range of phenotypes associated with 8p23.1 rearrangements is that REPP and REPD are not yet well characterized, probably due to their polymorphic status. Here, we describe a novel primate-specific gene family, named FAM90A (family with sequence similarity 90), found within these SDs. According to the current human reference sequence assembly, the FAM90A family includes 24 members along 8p23.1 region plus a single member on chromosome 12p13.31, showing copy number variation (CNV) between individuals. These genes can be classified into subfamilies I and II, which differ in their upstream and 5′-untranslated region sequences, but both share the same open reading frame and are ubiquitously expressed. Sequence analysis and comparative fluorescence in situ hybridization studies showed that FAM90A subfamily II suffered a big expansion in the hominoid lineage, whereas subfamily I members were likely generated sometime around the divergence of orangutan and African great apes by a fusion process. In addition, the analysis of the Ka/Ks ratios provides evidence of functional constraint of some FAM90A genes in all species. The characterization of the FAM90A gene family contributes to a better understanding of the structural polymorphism of the human 8p23.1 region and constitutes a good example of how SDs, CNVs and rearrangements within themselves can promote the formation of new gene sequences with potential functional consequences.

Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders

Eating disorders (EDs) are complex psychiatric diseases that include anorexia nervosa and bulimia nervosa, and have higher than 50% heritability. Previous studies have found association of BDNF and NTRK2 to ED, while animal models suggest that other neurotrophin genes might also be involved in eating behavior. We have performed a family-based association study with 151 TagSNPs covering 10 neurotrophin signaling genes: NGFB, BDNF, NTRK1, NGFR/p75, NTF4/5, NTRK2, NTF3, NTRK3, CNTF and CNTFR in 371 ED trios of Spanish, French and German origin. Besides several nominal associations, we found a strong significant association after correcting for multiple testing (P = 1.04 × 10−4) between ED and rs7180942, located in the NTRK3 gene, which followed an overdominant model of inheritance. Interestingly, HapMap unrelated individuals carrying the rs7180942 risk genotypes for ED showed higher levels of expression of NTRK3 in lymphoblastoid cell lines. Furthermore, higher expression of the orthologous murine Ntrk3 gene was also detected in the hypothalamus of the anx/anx mouse model of anorexia. Finally, variants in NGFB gene appear to modify the risk conferred by the NTRK3 rs7180942 risk genotypes (P = 4.0 × 10−5) showing a synergistic epistatic interaction. The reported data, in addition to the previous reported findings for BDNF and NTRK2, point neurotrophin signaling genes as key regulators of eating behavior and their altered cross-regulation as susceptibility factors for EDs.

The quest for a message: budding yeast, a model organism to study the control of pre-mRNA splicing

Removal of introns during pre-mRNA splicing is a critical process in gene expression, and understanding its control at both single-gene and genomic levels is one of the great challenges in Biology. Splicing takes place in a dynamic, large ribonucleoprotein complex known as the spliceosome. Combining Genetics and Biochemistry, Saccharomyces cerevisiae provides insights into its mechanisms, including its regulation by RNA-protein interactions. Recent genome-wide analyses indicate that regulated splicing is broad and biologically relevant even in organisms with a relatively simple intronic structure, such as yeast. Furthermore, the possibility of coordination in splicing regulation at genomic level is becoming clear in this model organism. This should provide a valuable system to approach the complex problem of the role of regulated splicing in genomic expression.

Amelioration of Duchenne muscular dystrophy in mdx mice by elimination of matrix-associated fibrin-driven inflammation coupled to the αMβ2 leukocyte integrin receptor

In Duchenne muscular dystrophy (DMD), a persistently altered and reorganizing extracellular matrix (ECM) within inflamed muscle promotes damage and dysfunction. However, the molecular determinants of the ECM that mediate inflammatory changes and faulty tissue reorganization remain poorly defined. Here, we show that fibrin deposition is a conspicuous consequence of muscle-vascular damage in dystrophic muscles of DMD patients and mdx mice and that elimination of fibrin(ogen) attenuated dystrophy progression in mdx mice. These benefits appear to be tied to: (i) a decrease in leukocyte integrin α(M)β(2)-mediated proinflammatory programs, thereby attenuating counterproductive inflammation and muscle degeneration; and (ii) a release of satellite cells from persistent inhibitory signals, thereby promoting regeneration. Remarkably, Fib-gamma(390-396A) (Fibγ(390-396A)) mice expressing a mutant form of fibrinogen with normal clotting function, but lacking the α(M)β(2) binding motif, ameliorated dystrophic pathology. Delivery of a fibrinogen/α(M)β(2) blocking peptide was similarly beneficial. Conversely, intramuscular fibrinogen delivery sufficed to induce inflammation and degeneration in fibrinogen-null mice. Thus, local fibrin(ogen) deposition drives dystrophic muscle inflammation and dysfunction, and disruption of fibrin(ogen)-α(M)β(2) interactions may provide a novel strategy for DMD treatment.

La revisió de textos escrits : Memòria de pràctiques a Núvol

Aquest TFG és la memòria de les pràctiques de revisió i correcció de textos escrits fetes al digital de cultura 'Núvol'. En la memòria faig una presentació i una anàlisi del digital, explico les tasques desenvolupades durant les pràctiques i en faig la valoració.

X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation

Background: Aproximately 5–10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects. Results: Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%). Conclusion:This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients.

Analysis of the multi-copy gene family FAM90A as a copy number variant in different ethnic backgrounds

Copy number variants contribute extensively to inter-individual genomic differences, but little is known about their inter-population variability and diversity. In a previous study (Bosch et al., 2007; 16:2572-2582), we reported that the primate-specific gene family FAM90A, which accounts for as many as 25 members in the human reference assembly, has expanded the number of FAM90A clusters across the hominoid lineage. Here we examined the copy number variability of FAM90A genes in 260 HapMap samples of European, African, and Asian ancestry, and showed significant inter-population differences (p<0.0001). Based on the recent study of Stranger et al. (2007; 315:848-853), we also explored the correlation between copy number variability and expression levels of the FAM90A gene family. Despite the high genomic variability, we found a low correlation between FAM90A copy number and expression levels, which could be due to the action of independent trans-acting factors. Our results show that FAM90A is highly variable in copy number between individuals and between populations. However, this variability has little impact on gene expression levels, thus highlighting the importance of genomic variability for genes located in regions containing segmental duplications.

Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)

Background: MLPA method is a potentially useful semi-quantitative method to detect copy number alterations in targeted regions. In this paper, we propose a method for the normalization procedure based on a non-linear mixed-model, as well as a new approach for determining the statistical significance of altered probes based on linear mixed-model. This method establishes a threshold by using different tolerance intervals that accommodates the specific random error variability observed in each test sample.Results: Through simulation studies we have shown that our proposed method outperforms two existing methods that are based on simple threshold rules or iterative regression. We have illustrated the method using a controlled MLPA assay in which targeted regions are variable in copy number in individuals suffering from different disorders such as Prader-Willi, DiGeorge or Autism showing the best performace.Conclusion: Using the proposed mixed-model, we are able to determine thresholds to decide whether a region is altered. These threholds are specific for each individual, incorporating experimental variability, resulting in improved sensitivity and specificity as the examples with real data have revealed.

Copy number variation in the porcine genome inferred from a 60 k SNP BeadChip

Background: Recent studies in pigs have detected copy number variants (CNVs) using the Comparative Genomic Hybridization technique in arrays designed to cover specific porcine chromosomes. The goal of this study was to identify CNV regions (CNVRs) in swine species based on whole genome SNP genotyping chips. Results: We used predictions from three different programs (cnvPartition, PennCNV and GADA) to analyze data from the Porcine SNP60 BeadChip. A total of 49 CNVRs were identified in 55 animals from an Iberian x Landrace cross (IBMAP) according to three criteria: detected in at least two animals, contained three or more consecutive SNPs and recalled by at least two programs. Mendelian inheritance of CNVRs was confirmed in animals belonging to several generations of the IBMAP cross. Subsequently, a segregation analysis of these CNVRs was performed in 372 additional animals from the IBMAP cross and its distribution was studied in 133 unrelated pig samples from different geographical origins. Five out of seven analyzed CNVRs were validated by real time quantitative PCR, some of which coincide with well known examples of CNVs conserved across mammalian species. Conclusions: Our results illustrate the usefulness of Porcine SNP60 BeadChip to detect CNVRs and show that structural variants can not be neglected when studying the genetic variability in this species.

Copy number variations of colorectal cancer by whole exome sequencing data

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death worldwide. About 85% of the cases of CRC are known to have chromosomal instability, an allelic imbalance at several chromosomal loci, and chromosome amplification and translocation. The aim of this study is to determine the recurrent copy number variant (CNV) regions present in stage II of CRC through whole exome sequencing, a rapidly developing targeted next-generation sequencing (NGS) technology that provides an accurate alternative approach for accessing genomic variations. 42 normal-tumor paired samples were sequenced by Illumina Genome Analyzer. Data was analyzed with Varscan2 and segmentation was performed with R package R-GADA. Summary of the segments across all samples was performed and the result was overlapped with DEG data of the same samples from a previous study in the group1. Major and more recurrent segments of CNV were: gain of chromosome 7pq(13%), 13q(31%) and 20q(75%) and loss of 8p(25%), 17p(23%), and 18pq(27%). This results are coincident with the known literature of CNV in CRC or other cancers, but our methodology should be validated by array comparative genomic hybridisation (aCGH) profiling, which is currently the gold standard for genetic diagnosis of CNV.

Copy&Paste façanes procedurals per skylineEngine

L’objectiu d’aquest projecte és el desenvolupament d’una eina d’alt nivell pel modelatged’edificis procedurals que permeti copiar i enganxar parts arbitràries d’un edifici en un altre.Els edificis procedurals es basen en l’execució iterativa d’un conjunt de regles, que es podenrepresentar per un graf d’operacions. Per tant, l’operació de copiar i enganxar es centra enla reescriptura dels grafs de regles amb l’objectiu de modificar els edificis per tal de duraquesta tasca. Donat que es treballa sobre la plataforma de recerca anomenada skylineEngine,que s’executa sobre el programari Houdini 3D, l’aplicació també estarà implementada a sobred’aquesta plataforma

Sistemas de detección y extracción semiautomática de siglas: estado de la cuestión

Informe de investigación realizado a partir de una estancia en el Équipe de Recherche en Syntaxe et Sémantique de la Université de Toulouse-Le Mirail, Francia, entre julio y setiembre de 2006. En la actualidad existen diversos diccionarios de siglas en línea. Entre ellos sobresalen Acronym Finder, Abbreviations.com y Acronyma; todos ellos dedicados mayoritariamente a las siglas inglesas. Al igual que los diccionarios en papel, este tipo de diccionarios presenta problemas de desactualización por la gran cantidad de siglas que se crean a diario. Por ejemplo, en 2001, un estudio de Pustejovsky et al. mostraba que en los abstracts de Medline aparecían mensualmente cerca de 12.000 nuevas siglas. El mecanismo de actualización empleado por estos recursos es la remisión de nuevas siglas por parte de los usuarios. Sin embargo, esta técnica tiene la desventaja de que la edición de la información es muy lenta y costosa. Un ejemplo de ello es el caso de Abbreviations.com que en octubre de 2006 tenía alrededor de 100.000 siglas pendientes de edición e incorporación definitiva. Como solución a este tipo de problema, se plantea el diseño de sistemas de detección y extracción automática de siglas a partir de corpus. El proceso de detección comporta dos pasos; el primero, consiste en la identificación de las siglas dentro de un corpus y, el segundo, la desambiguación, es decir, la selección de la forma desarrollada apropiada de una sigla en un contexto dado. En la actualidad, los sistemas de detección de siglas emplean métodos basados en patrones, estadística, aprendizaje máquina, o combinaciones de ellos. En este estudio se analizan los principales sistemas de detección y desambiguación de siglas y los métodos que emplean. Cada uno se evalúa desde el punto de vista del rendimiento, medido en términos de precisión (porcentaje de siglas correctas con respecto al número total de siglas extraídas por el sistema) y exhaustividad (porcentaje de siglas correctas identificadas por el sistema con respecto al número total de siglas existente en el corpus). Como resultado, se presentan los criterios para el diseño de un futuro sistema de detección de siglas en español.

Recepción y difusión internacionales de Mercè Rodoreda: obra original, crítica y traducción

RESUM Recepción y difusión internacionales de Mercè Rodoreda: obra original, crítica y traducción té per objecte determinar la recepció i la difusió de l’obra original de Mercè Rodoreda, així com de l’obra crítica i de les traduccions, en el context internacional a partir de la interpretació de quatre bases de dades: obra literària de Mercè Rodoreda, obra crítica de Mercè Rodoreda i la seva obra, traductors i traduccions en funció de la llengua i de l’obra i, per últim, presència documental de Mercè Rodoreda a les Biblioteques Nacionals del món. El treball de recerca s’estructura de la següent manera. En primer lloc, plantegem i delimitem el tema, els objectius, la metodologia i la descripció de les bases de dades. Acte seguit, interpretem les bases de dades i exposem algunes consideracions. A continuació, presentem les conclusions finals que hem desenvolupat en cadascun dels àmbits en els que se centra la nostra recerca, així com el projecte de tesi doctoral i les noves línies de recerca. Per últim, exposem la bibliografia i els annexes, en els que incloem les bases de dades i reproduim els estudis traductològics comentats en el treball. Amb l’elaboració d’aquest treball de recerca pretenem, entre d’altres, donar a conèixer els gèneres literaris que va cultivar Mercè Rodoreda; recopilar l’obra crítica al voltant de l’autora i distingir la seva temàtica per determinar el nombre d’estudis crítics sobre traducció; identificar quins títols de l’obra de Mercè Rodoreda s’han traslladat a altres llengües, així com confirmar quina és l’obra més traduïda i quines les llengües a les que s’ha traslladat la seva obra; i, per últim, constatar la presència d’obres originals, estudis crítics i traduccions a les Biblioteques Nacionals del món i identificar-ne les possibles àrees d’expansió.

Pessebre virtual: disseny i exportació

Aquest projecte és una part d’un projecte més ampli consistent en estudiar un format gràfic que permeti exportar una escena modelada en Blender i importar aquesta mateixa escena en un entorn interactiu basat en Visual C++ amb OpenGL. D’aquesta forma, disposem de la capacitat de modelat de Blender i de la interacció i visualització de la llibreria OpenGL. Aquest format ha de representar geometria i textures imprescindiblement, i si és possible, d’altres factors importants com il·luminació, visualització i moviment. La part del projecte explicada en aquesta memòria consisteix en estudiar el format gràfic més adient per representar els diferents factors de realisme de l’escena (geometria, textura, etc.) havent triat el format OBJ per la seva capacitat de representació i fàcil edició. Per a provar el format, s’ha dissenyat un diorama de pessebre utilitzant les capacitats de modelatge de Blender. Pel que respecta les figures, aspecte important per a considerar l’escena com a pessebre, s’ha utilitzat un escàner 3D que ha obtingut representacions de malla 3D, a partir de figures reals de pessebre, que posteriorment han estat texturades. S’ha generat un vídeo del diorama de pessebre que permet veure’n tots els detalls navegant amb el punt de vista per l’escena. Aquest vídeo s’ha exposat en la mostra de pessebres de la Associació Pessebrista de Sabadell el Nadal del 2008.

La evolución de la publicidad en el siglo XX: ¿El paso de una publicidad racional a una publicidad emotiva?

El present treball d’investigació reflexionarà sobre els canvis i l’evolució de la publicitat al llarg del segle XX. Per això, partirem des del punt d’inflexió que va suposar un dels millors anuncis gràfics de la història i possiblement, el que s’ha considerat l’anunci gràfic d’automòbil més important: Think Small. D’aquest punt repassarem i compararem les teories, els testimonis i les obres dels més importants redactors publicitaris dels últims 100 anys. (Des de Bernbach, Ogilvy, Reeves, Rubicam, Burnett fins a Moliné, Lorente, Bassat i Segarra). Afrontarem la dicotomia històrica entre aquells teòrics que van defensar la publicitat racional i la tipologia d’anuncis de caire informatiu enfront aquells que es basaren en el dramatisme i els anuncis emocionals en un prisma diagonal del qual esdevindran alguns dels conceptes, tècniques i teories claus que conformen la història de la publicitat: USP, AIDA, Imatge de marca, Posicionament, Copy Platform, Anunci Natural, etc. Es prestarà una especial atenció a algunes de les obres mestres de la publicitat en els últims temps, com les campanyes: ¿Te gusta conducir? o Be Water My Friend, ambdues de BMW, així com un específic repàs a les tendències de l’agència de publicitat DDB i les seves campanyes d’Audi i Volkswagen per desentranyar les influències de la coneguda com a Revolució Creativa que encara persisteixen en les seves obres. Farem èmfasi en l’aparició de la Televisió i posteriorment, del fenomen Internet i altres canvis que s’han produït en la tècnica, la producció i el muntatge. Tot això, finalment, respondrà a la pregunta: Ha existit el canvi d’una publicitat racional a una publicitat emotiva?