Genomic architecture of sickle cell disease clinical variation in children from West Africa : a case-control study design

Contexte : L’anémie falciforme ou drépanocytose est un problème de santé important, particulièrement pour les patients d’origine africaine. La variation phénotypique de l’anémie falciforme est problématique pour le suivi et le traitement des patients. L’architecture génomique responsable de cette variabilité est peu connue. Principe : Mieux saisir la contribution génétique de la variation clinique de cette maladie facilitera l’identification des patients à risque de développer des phénotypes sévères, ainsi que l’adaptation des soins. Objectifs : L’objectif général de cette thèse est de combler les lacunes relatives aux connaissances sur l’épidémiologie génomique de l’anémie falciforme à l’aide d’une cohorte issue au Bénin. Les objectifs spécifiques sont les suivants : 1) caractériser les profils d’expressions génomiques associés à la sévérité de l’anémie falciforme ; 2) identifier des biomarqueurs de la sévérité de l’anémie falciforme ; 3) identifier la régulation génétique des variations transcriptionelles ; 4) identifier des interactions statistiques entre le génotype et le niveau de sévérité associé à l’expression ; 5) identifier des cibles de médicaments pour améliorer l’état des patients atteints d’anémie falciforme. Méthode : Une étude cas-témoins de 250 patients et 61 frères et soeurs non-atteints a été menée au Centre de Prise en charge Médical Intégré du Nourrisson et de la Femme Enceinte atteints de Drépanocytose, au Bénin entre février et décembre 2010. Résultats : Notre analyse a montré que des profils d’expressions sont associés avec la sévérité de l’anémie falciforme. Ces profils sont enrichis de génes des voies biologiques qui contribuent à la progression de la maladie : l’activation plaquettaire, les lymphocytes B, le stress, l’inflammation et la prolifération cellulaire. Des biomarqueurs transcriptionnels ont permis de distinguer les patients ayant des niveaux de sévérité clinique différents. La régulation génétique de la variation de l’expression des gènes a été démontrée et des interactions ont été identifiées. Sur la base de ces résultats génétiques, des cibles de médicaments sont proposées. Conclusion: Ce travail de thèse permet de mieux comprendre l’impact de la génomique sur la sévérité de l’anémie falciforme et ouvre des perspectives de développement de traitements ciblés pour améliorer les soins offerts aux patients.

Identification of Genomic Variants Associated with Adolescent Idiopathic Scoliosis (AIS) in French-Canadian Population

La scoliose idiopathique est une déformation tridimensionnelle de la colonne vertébrale dont la pathogenèse reste obscure. Cette maladie affecte 2-4% des adolescents de 10-18 ans parmi les garçons et les filles. Il est à noter que les filles sont plus sévèrement affectées et ce en plus grand nombre que les garçons. Les études de jumeaux ont montré que les facteurs génétiques jouent un rôle important dans la scoliose idiopathique de l'adolescent (SIA). Depuis 2010, les études d'association pan génomiques ont été multipliées dans les recherches, visant à trouver des gènes candidats impliqués dans la SIA à travers des examens des polymorphismes nucléotidiques (SNPs). Un test génétique nommé "ScoliScore" a été publié pour essayer de prédire la progression de courbure dans la population caucasienne. Cependant, l'association n'a pas été reproduite dans une grande étude japonaise, soulignant l'importance d'une étude de réplication dans une population caucasienne indépendante. Dans ce contexte, mon projet de maîtrise a permis de génotyper plus de 1,4 millions de SNPs dans une cohorte canadienne-française dans le but: 1) de valider l'association de ScoliScoreTM; et 2) d’identifier les variants génomiques associées à la SIA dans la population québécoise. Notre étude a montré qu’aucun des variants constituant le test ScoliScoreTM n’était associé à la SIA. Ceci suggère que l'absence d'association dans une cohorte japonaise n'est pas due à l'appartenance ethnique. Aussi, nous avons identifié des variants génomiques associés significativement à l’initiation et/ou la progression de SIA dans la population québécoise, suggérant des gènes candidats impliqués dans la pathogenèse de SIA.

Mémoire de la disparition : "Récits d’Ellis Island", l’album

Compte rendu de l'album « Récits d'Ellis Island : histoires d'errance et d'espoir » (POL, 1994).

Macrobenthos of Minicoy Island, Lakshadweep

In this present study macro benthos of minicoy island lakshadweep, an attempt has been made to study the distribution and community structure of benthos at different ecosystems. The main objectives of the study include the identification of benthic fauna, their distribution and composition, standing stock, qualitative and quantitative nature in relation to hydrography,seasons and sediment texture, community structure analysis and tropic relationships. This base line study at Minicoy,thus establishes that the benthos of sea grass and mangrove ecosystems(nursery grounds) determines the richness and diversity of demersal fish fauna at the nearby lagoon and reef areas to a great extent. Any serious stress on these ecosystems may lead to disappearance of certain fish species in the nearby future

Coastal and ground water pollution in Kavaratti island, Lakshadweep sea

The tiniest Union territory of India, Lakshadweep, is an archipelago, with an area of 32 Sq. km. consisting of 12 atolls, three reefs and five submerged banks, lies between 8° and 12°30'N latitudes and 71° and 74" E longitudes. It is one of the most important and critical territories of India from economic and defence point of view. Specialised environment having typical geological set up, Lakshadweep is ecologically sensitive to even slight climatic or anthropogenic interference. Pollution of coastal seas, over exploitation and contamination of the fresh water sources are thus become great concerns to the existence of the island. Typical geological set up and interference cause threat to the ecology of the fragile environment and resources of the island as well as its resources. Marine pollution and ground water contamination are concerns in this regard. Even though attentions were made to assess the physico—chemical and bacteriological status of the marine and groundwater systems separately, an integrated approach has not been evolved. The present study with its broad objectives is attempted for an integrated assessment of microbiological, physicochemical and biological characteristics of the surrounding seawater and microbiological and physico—chemical characteristics of the ground water in Kavaratti island. The entire study has been organised in 4 chapters

Integrated Coastal Water Quality Assessment Of Andrott Island, Lakshadweep

Assessment water’ quality nowa-days in global scenario implies the need for a reference point against which monitoring can be measured and weighed. Aquatic ecosystenis as part of the natural environment are balanced both witliin tlicinselves and with other environmental compartments and this equilibrium is subject to natural variations and evolutions as well as variations caused by human intervention. The present assessnient is to identify. and possibly quantify, anthropogenic influences over time against a “natural baseline situation. Water pollution problems have only recently been taken seriously in retrospect. Once damage occurred, it becomes immeasurable, and control action cannot be initiated

Development of a Fully Automated Image Analysis Method for High Density cDNA and array CGH Microarray Based Genomic Studies

In this thesis, different techniques for image analysis of high density microarrays have been investigated. Most of the existing image analysis techniques require prior knowledge of image specific parameters and direct user intervention for microarray image quantification. The objective of this research work was to develop of a fully automated image analysis method capable of accurately quantifying the intensity information from high density microarrays images. The method should be robust against noise and contaminations that commonly occur in different stages of microarray development.

Enlarging a training set for genomic selction by imputation of un-genotyped animals in populations of varying genetic architecture

Background: The most common application of imputation is to infer genotypes of a high-density panel of markers on animals that are genotyped for a low-density panel. However, the increase in accuracy of genomic predictions resulting from an increase in the number of markers tends to reach a plateau beyond a certain density. Another application of imputation is to increase the size of the training set with un-genotyped animals. This strategy can be particularly successful when a set of closely related individuals are genotyped. ----- Methods: Imputation on completely un-genotyped dams was performed using known genotypes from the sire of each dam, one offspring and the offspring’s sire. Two methods were applied based on either allele or haplotype frequencies to infer genotypes at ambiguous loci. Results of these methods and of two available software packages were compared. Quality of imputation under different population structures was assessed. The impact of using imputed dams to enlarge training sets on the accuracy of genomic predictions was evaluated for different populations, heritabilities and sizes of training sets. ----- Results: Imputation accuracy ranged from 0.52 to 0.93 depending on the population structure and the method used. The method that used allele frequencies performed better than the method based on haplotype frequencies. Accuracy of imputation was higher for populations with higher levels of linkage disequilibrium and with larger proportions of markers with more extreme allele frequencies. Inclusion of imputed dams in the training set increased the accuracy of genomic predictions. Gains in accuracy ranged from close to zero to 37.14%, depending on the simulated scenario. Generally, the larger the accuracy already obtained with the genotyped training set, the lower the increase in accuracy achieved by adding imputed dams. ----- Conclusions: Whenever a reference population resembling the family configuration considered here is available, imputation can be used to achieve an extra increase in accuracy of genomic predictions by enlarging the training set with completely un-genotyped dams. This strategy was shown to be particularly useful for populations with lower levels of linkage disequilibrium, for genomic selection on traits with low heritability, and for species or breeds for which the size of the reference population is limited.

Genomic architecture of adaptive color pattern divergence and convergence in Heliconius butterflies

Identifying the genetic changes driving adaptive variation in natural populations is key to understanding the origins of biodiversity. The mosaic of mimetic wing patterns in Heliconius butterflies makes an excellent system for exploring adaptive variation using next-generation sequencing. In this study, we use a combination of techniques to annotate the genomic interval modulating red color pattern variation, identify a narrow region responsible for adaptive divergence and convergence in Heliconius wing color patterns, and explore the evolutionary history of these adaptive alleles. We use whole genome resequencing from four hybrid zones between divergent color pattern races of Heliconius erato and two hybrid zones of the co-mimic Heliconius melpomene to examine genetic variation across 2.2 Mb of a partial reference sequence. In the intergenic region near optix, the gene previously shown to be responsible for the complex red pattern variation in Heliconius, population genetic analyses identify a shared 65-kb region of divergence that includes several sites perfectly associated with phenotype within each species. This region likely contains multiple cis-regulatory elements that control discrete expression domains of optix. The parallel signatures of genetic differentiation in H. erato and H. melpomene support a shared genetic architecture between the two distantly related co-mimics; however, phylogenetic analysis suggests mimetic patterns in each species evolved independently. Using a combination of next-generation sequencing analyses, we have refined our understanding of the genetic architecture of wing pattern variation in Heliconius and gained important insights into the evolution of novel adaptive phenotypes in natural populations.

I Shall Show you my island, you will show me your country. 'Yo te mostraré mi isla y tu me mostrarás tu país'.

El proyecto arranca de una idea central que consiste en programar todas las clases de inglés que correspondan a los dos ciclos de la ESO, partiendo de dos realidades culturales, como son: -la isla en la que vive el alumno con sus implicaciones en la región 'I shall show you my island'. -El lugar donde se habla la lengua, objeto de aprendizaje (inglés) 'You will show me your country'. El grupo de trabajo está compuesto por 19 docentes tanto de EGB como de bachillerato, y pertenecen a la isla de La Palma todos ellos. El objetivo general que se propone es lograr desarrollar las capacidades de los alumnos en los ámbitos cognitivos, afectivos y sociales tomando como base para su logro las vivencias que el medio en que se desarrollan les son consustanciales con su propia vida. Desde un principio se propuso llevar a cabo una unidad didáctica conectada al 'proyecto general', de tal manera que fuese coherente y siguiese una línea general y espiral con el resto de las once unidades restantes que forman en su conjunto todo el proyecto de enseñanza de la ESO. La unidad didáctica como un 'todo' organizado no se ha llevado a la práctica este curso, sin embargo a medida que se iba elaborando material, se iba investigando en el aula. Además de la aportación de la asesora de inglés, este trabajo se ha apoyado en: libros de texto, revistas pedagógicas, material de reprografía, medios informáticos, etc. En cuanto a la valoración del proyecto ha sido muy positiva tanto por el propio grupo de trabajo como por el público asistente a las Jornadas de Innovación celebradas en La Palma y donde pudo presentarse la experiencia..

Etnic discrimination and income in San Andrés Island, Colombia

This document examines, bases on the analysis of observable characteristics, if an income gapexists between the raizal population and non raizal population of San Andres Island. For thispurpose, the information of the SISBEN II survey for the year 2004, compelled by the NationalPlanning Department (DNP, Spanish acronym) is used. The methodological strategy uses quantileregressions to determine the existence of pay gaps throughout the distribution of income. Theresults suggest that being raizal has a negative impact on income for the lower quantiles. However,this difference vanishes as income increases, becoming positive at higher levels.

Super Mario en Monkey Island : exploración, narración y representación en los videojuegos.

El autor hace un detallado recorrido por el mundo de los videojuegos desde los primeros modelos hasta la actualidad para darnos a conocer, entre otros, los videojuegos narrativos. Siendo la repetición una de las características típicas de los videojuegos, es através de ella que los niños pueden aprender bien en sentido positivo: superación del fracaso, perseverancia, etcétera; bien en sentido negativo: sexismo, capitalismo ambicioso, etcétera.

Green Island.

Pertenece a un amplio programa infantil de lectura que abarca distintos niveles de edad y, por tanto, de conocimientos. Se abordan las necesidades de lectura en los niños y la amplia variedad de habilidades que necesitan adquirir para su aprendizaje y, se destaca, también, la importancia de la narración en las historias. Aparecen dos nuevos personajes, Nadim y Anneena, que junto con Biff, Chip y Kipper colaboran para evitar la contaminación de la isla verde.

Facebook como espacio de aprendizaje de ELE en el contexto island??s y su efecto en el proceso de lectoescritura

Resumen basado en el de la publicaci??n