Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

WebGC Gossiping on Browsers without a Server [Live Demo/Poster]

International audience1 Decentralized social networks have attracted the attention of a large number of researchers with their promises of scalability, privacy , and ease of adoption. Yet, current implementations require users to install specific software to handle the protocols they rely on. The WebRTC framework holds the promise of removing this requirement by making it possible to run peer-to-peer applications directly within web browsers without the need of any external software or plugins. In this demo, we present WebGC, a WebRTC-based library that supports gossip-based communication between web browsers and enables them to operate with Node-JS applications. Due to their inherent scalability, gossip-based protocols constitute a key component of a large number of decentralized applications including social networks. We therefore hope that WebGC can represent a useful tool for developers and researchers

Problème d'acquisition de données par une torpille

National audiencePapier court portant sur une première étude et modélisation du problème d'acquisition de données par une torpille sous-marine. Cette torpille a comme objectif d'effectuer différents relevés, d'analyser la topologie du fond sous-marin, ou encore faire de la cartographie. Une fois la torpille en immersion, elle va recevoir de manière aléatoire différents groupes de tâches à réaliser dans un certain ordre sur son monoprocesseur. Ces tâches vont devoir être réalisées de manière périodique jusqu'à la fin de l'expérience. Une analyse stochastique va permettre de décider de la faisabilité de ce problème

WebGC: Browser-Based Gossiping [Live Demo/Poster]

International audienceThe advent of browser-to-browser communication technologies like WebRTC has renewed interest in the peer-to-peer communication model. However, the available WebRTC code base still lacks im-portant components at the basis of several peer-to-peer solutions. We tackle this problem by proposing WebGC, a library for gossip-based communication between web browsers. Due to their inher-ent scalability, gossip-based, or epidemic protocols constitute a key component of a large number of decentralized applications. We-bGC thus represents an important step towards their wider spread

Asymmetric outcome of community coalescence of seed and soil microbiota during early seedling growth

Seed microbial community constitutes a primary inoculum for plant microbiota assembly. Still, the persistence of seed microbiota when seeds encounter soil during plant emergence and early growth is barely documented. Here, we characterized the interchange event or coalescence of seed and soil microbiota and how it structured seedling bacterial and fungal communities. We performed eight contrasted coalescence events to identify drivers influencing seedling microbiota assembly: four seed lots of two Brassica napus genotypes were sown in two soils of contrasted diversity. We found that seedling root and stem microbiota were influenced by soil diversity but not by initial seed microbiota composition. A strong selection on the two-source communities occurred during microbiota assembly, with only 8-32% of soil taxa and 0.8-1.4% of seed-borne taxa colonizing seedlings. The recruitment of seedling microbiota came mainly from soil (35-72% of diversity) and not from seeds (0.3-15%). The outcome of seed and soil microbiota coalescence is therefore strongly asymmetrical with a dominance of soil taxa. Interestingly, seedling microbiota was primarily composed of initially rare taxa (from seed, soil or unknown origin) and sub-dominant soil taxa. Our results suggest that plant microbiome engineering success based on native seed or soil microbiota will rely on rare and sub-dominant taxa in source communities

Transmission of Seed and Soil Microbiota to Seedling

International audienceThe seed microbial community constitutes an initial inoculum for plant microbiota assembly. Still, the persistence of seed microbiota when seeds encounter soil during plant emergence and early growth is barely documented. We characterized the encounter event of seed and soil microbiota and how it structured seedling bacterial and fungal communities by using amplicon sequencing. We performed eight contrasting encounter events to identify drivers influencing seedling microbiota assembly. To do so, four contrasting seed lots of two Brassica napus genotypes were sown in two soils whose microbial diversity levels were manipulated by serial dilution and recolonization. Seedling root and stem microbiota were influenced by soil but not by initial seed microbiota composition or by plant genotype. A strong selection on the seed and soil communities occurred during microbiota assembly, with only 8% to 32% of soil taxa and 0.8% to 1.4% of seed-borne taxa colonizing seedlings. The recruitment of seedling microbiota came mainly from soil (35% to 72% of diversity) and not from seeds (0.3% to 15%). Soil microbiota transmission success was higher for the bacterial community than for the fungal community. Interestingly, seedling microbiota was primarily composed of initially rare taxa (from seed, soil, or unknown origin) and intermediate-abundance soil taxa

Single seed microbiota: assembly and transmission from parent plant to seedling

Abstract Gaining basic understanding of processes involved in seed microbiota assembly is a prerequisite for improving crop establishment. Investigation of microbiota structure during seed development revealed that individual seeds of bean and radish were associated with a dominant bacterial taxon representing more than 75% of all reads. The identity of this taxon was highly variable between plants and within seeds of the same plant. Succession of dominant taxa occurred during seed filling and maturation through Selection . In a second step, we evaluated seed to seedling transmission of these dominant seed-borne taxa. We showed that initial bacterial abundance on seeds was not a good predictor of seedling transmission and that the identity of seed-borne taxa can impact seedling phenotype. Altogether this work unveiled that seeds are colonized by few bacterial taxa of highly variable identity, which appears to be important for the early stages of plant development