Population genomics of picophytoplankton unveils novel chromosome hypervariability

Tiny photosynthetic microorganisms that form the picoplankton (between 0.3 and 3 mm in diameter) are at the base of the food web in many marine ecosystems, and their adaptability to environmental change hinges on standing genetic variation. Although the genomic and phenotypic diversity of the bacterial component of the oceans has been intensively studied, little is known about the genomic and phenotypic diversity within each of the diverse eukaryotic species present. We report the level of genomic diversity in a natural population of Ostreococcus tauri (Chlorophyta, Mamiellophyceae), the smallest photosynthetic eukaryote. Contrary to the expec- tations of clonal evolution or cryptic species, the spectrum of genomic polymorphism observed suggests a large panmictic population (an effective population size of 1.2 × 107) with pervasive evidence of sexual reproduction. De novo assemblies of low-coverage chromosomes reveal two large candidate mating-type loci with suppressed recom- bination, whose origin may pre-date the speciation events in the class Mamiellophyceae. This high genetic diversity is associated with large phenotypic differences between strains. Strikingly, resistance of isolates to large double- stranded DNA viruses, which abound in their natural environment, is positively correlated with the size of a single hypervariable chromosome, which contains 44 to 156 kb of strain-specific sequences. Our findings highlight the role of viruses in shaping genome diversity in marine picoeukaryotes

A novel locus (CORD12) for autosomal dominant cone-rod dystrophy on chromosome 2q24.2-2q33.1

<p>Abstract</p> <p>Background</p> <p>Rod-cone dystrophy, also known as retinitis pigmentosa (RP), and cone-rod dystrophy (CRD) are degenerative retinal dystrophies leading to blindness. To identify new genes responsible for these diseases, we have studied one large non consanguineous French family with autosomal dominant (ad) CRD.</p> <p>Methods</p> <p>Family members underwent detailed ophthalmological examination. Linkage analysis using microsatellite markers and a whole-genome SNP analysis with the use of Affymetrix 250 K SNP chips were performed. Five candidate genes within the candidate region were screened for mutations by direct sequencing.</p> <p>Results</p> <p>We first excluded the involvement of known adRP and adCRD genes in the family by genotyping and linkage analysis. Then, we undertook a whole-genome scan on 22 individuals in the family. The analysis revealed a 41.3-Mb locus on position 2q24.2-2q33.1. This locus was confirmed by linkage analysis with specific markers of this region. The maximum LOD score was 2.86 at θ = 0 for this locus. Five candidate genes, <it>CERKL</it>, <it>BBS5, KLHL23, NEUROD1</it>, and <it>SF3B1 </it>within this locus, were not mutated.</p> <p>Conclusion</p> <p>A novel locus for adCRD, named <it>CORD12</it>, has been mapped to chromosome 2q24.2-2q33.1 in a non consanguineous French family.</p

Design and development of a support system for clinical diagnosis and genetic retinitis pigmentosa

Le diagnostic des rétinopathies pigmentaires pose différents problèmes, au niveau clinique comme au niveau moléculaire. En premier lieu, il s'agit de maladies rares, la faible prévalence de chaque pathologie à l'échelle de la population mondiale rend difficile leur étude. En second lieu, la caractérisation phénotypique de ces maladies est délicate car les symptômes qui en découlent s'avèrent très similaires. De manière liée, l'œil et le processus de la vision s'avèrent complexes et impliquent les produits d'expression de nombreux gènes. Ainsi, bien que les rétinopathies soient majoritairement monogénique et respectent le modèle d'hérédité mendélienne, les causes génétiques des maladies sont variées. Sur la base de ce double constat, nous proposons deux approches méthodologiques complémentaires menant à une meilleure compréhension de ce groupe de pathologies. Une première approche a pour finalité l'acquisition du jeu exhaustif des gènes impliqués. Les travaux portent sur l'exploitation des puces de génotypage. Nous effectuons une étude de liaison génétique entre les variations ponctuelles et les pathologies. Une seconde approche porte sur la représentation des connaissances associées aux phénotypes cliniques. Un composant ontologique est construit afin d'expliciter les savoirs nécessaires au diagnostic. Les données collectées sur le long terme par les experts sont étiquetées au travers de termes organisés au sein d'un thésaurus dédié. Les profils cliniques des patients et des maladies sont manipulés sous forme de collections de caractéristiques et comparés au moyen d'une mesure de similarité adaptée. L'objectif est alors de proposer un système d'aide au diagnostic.Diagnosis of retinitis pigmentosa could be difficult regarding both to clinics or molecular issues. Firstly, there are rare diseases, so the prevalence of each pathology in the world population is very low. Secondly, the symptoms of diseases are very similar, so their phenotypic characterization is hard. Moreover, the eye and the visual process are complex and numerous genes' products are implicated. Although retinopathies are mainly monogenic and mendelian inherited diseases, the polymorphisms involved in these diseases are very diverse.These both observations lead us to develop two complementary methodological approaches in a view to better understand the retinopathies.The first approach aims to identify all the genes involved in the diseases using genotyping chips. For this purpose, we studied genetic linkage between single nucleotide variations and pathologies. The second approach leads to the representation of clinical knowledge. An ontological compound was built to make explicit the knowledge involved in the process of diagnosis. The data previously collected by experts were labeled by terms that were organized in a specific thesaurus. The clinic profiles of the patients and diseases were handled as features collections and were compared by similarity calculations. The goal of this work is to build a knowledge-based system for diagnosis

MetaTreeMap: An Alternative Visualization Method for Displaying Metagenomic Phylogenic Trees.

Metagenomic samples can contain hundreds or thousands of different species. The most common method to identify these species is to sequence the samples and then classify the reads to nodes along a phylogenic tree. Linear representations of trees with so many nodes face legibility issues. In addition, such views are not optimal for appreciating the read quantity assigned to each node. The problem is exaggerated when comparison between multiple samples is needed. MetaTreeMap adapts a visualization method that addresses these weaknesses. The tree is represented by nested rectangles that illustrate the number or percentage of assigned reads. MetaTreeMap implements various options specific to phylogenic trees that allow for quick overview and investigation of the information. More generally, the goal of this software is to provide the user with the ability to easily display phylogenic trees based on various quantities assigned to the nodes, such as read number, percentage or other values. The tool can be used online at http://metasystems.riken.jp/visualization/treemap/

Construction of the MetaTreeMap data structure.

<p>(a) Trees representing the two datasets to be compared. (b) Merged tree constructed by the software. Circles are nodes, squares are assigned reads. From the initial datasets (black), MetaTreeMap creates a skeleton tree (blue) with leaves (green).</p

ScripTree: scripting phylogenetic graphics

International audienceThere is a large amount of tools for interactive display of phylogenetic trees. However, there is a shortage of tools for the automation of tree rendering. Scripting phylogenetic graphics would enable the saving of graphical analyses involving numerous and complex tree handling operations and would allow the automation of repetitive tasks. ScripTree is a tool intended to fill this gap. It is an interpreter to be used in batch mode. Phylogenetic graphics instructions, related to tree rendering as well as tree annotation, are stored in a text file and processed in a sequential way. AVAILABILITY: ScripTree can be used online or downloaded at www.scriptree.org, under the GPL license. IMPLEMENTATION: ScripTree, written in Tcl/Tk, is a cross-platform application available for Windows and Unix-like systems including OS X. It can be used either as a stand-alone package or included in a bioinformatic pipeline and linked to a HTTP server

Functional annotation of polymorphisms identified by NGS approaches in P.falciparum

National audienceMalaria is one of the most widespread parasitic infections in the world. The ongoing WHO Malaria elimination program has resulted in decreased cases. These encouraging results are the issue of public health policies and development of artemisinin based therapies. These approaches are now threatened by the emergence of artemisinin resistant parasites. The development of resistant assay (RSA test, [3]) and genetic markers (Kelch gene, [1]) enable us to better evaluate the prevalence of artemisinin resistant isolates in Cambodia. Plasmodium falciparum is one the major causative agent of malaria in Cambodia. The focus of this project is to identify drug resistant genes in the malaria parasite P.falciparum. It aims to identify these genes using genome polymorphisms. We use a large datasets to analyse the distribution of parasite population over the country. The set is based on NGS genome sequences available in ENA database. We recover 167 genomes originating from four different localities in Cambodia. We describe a reliable SNP variant calling pipeline from around 200 NGS genome sequences based on quantitative parameters provided in the VCF files. SNPs were extracted and filtered after comparison with 3D7 reference genome. Different tools like R, Perl and Artemis were used for the analysis. The major steps involved in the pipeline are, a) The quantitative parameters provided in the variant calling format (VCF) files were analysed to define a threshold to select good quality SNPs, b) SNPs were filtered based on MQ which represents the mapping quality and DA (� ALT / � DP4) which represents the percentage of high quality ALT reads, c) SNPs with low frequency and SNPs with uncertain ALT bases were not considered, d) Mapping was done to different genome version and annotation information was provided for each SNP. These SNPs were then characterized into three categories: non coding region, synonymous and non-synonymous. We differentiate SNPs associated to the coding core and to the sub-telomeric regions of the genome. The large number of samples indeed improves SNP extraction. The dataset obtained with the variant calling pipeline was compared to the other published datasets and validated with the presence of marker SNPs. Recent studies provide evidence that sub-populations of parasites are present in Cambodia [2]. We probe this hypothesis using SNP dataset extracted with pipeline as described above. Different set of SNPs were tested to evaluate the robustness of the sub-population including mutations in the Kelch gene that are being associated to the resistance to artemisinin derivatives. This genetic marker is found in large numbers in the region of Pailin, where drug resistance was first described. We provide genetic evidence for acquisition and transmission of artemisinin resistance in Cambodian parasite sub-populations. These results question the origin and the persistence of these sub-populations. Fragmentation of the P. falciparum is important information that must be taken into account for further statistical analysis of SNP distribution. Different approaches using bioinformatics resources and SNP data will be established to identify features providing functional annotation for proteins, pathways, isolates and sub-populations. These steps are essential to identify parasite sub-populations that could be more susceptible to acquire and to transmit drug resistance in Cambodia

Additional file 1: Table S1. of Transcriptomic study of Salmonella enterica subspecies enterica serovar Typhi biofilm

Expression data for all genes found to be statistically significant. (DOCX 47 kb