Sprachliche Praktiken im ein- und zweisprachigen Kindergarten des Kantons Graubünden: eine ethnographische Studie

Mit dem Thema der Sprache greift das Dissertationsprojekt ein in den letzten Jahren vermehrt im Interesse der Bildungsforschung und -politik stehendes Thema der frühkindlichen Bildung auf. Die zunehmende sprachliche Heterogenität der Gesellschaft auf der einen Seite und die im Untersuchungsgebiet historisch gewachsene Mehrsprachigkeit auf der anderen Seite werden im Kontext des Bildungssystems oftmals als Herausforderung wahrgenommen. Im dreisprachigen Kanton Graubünden mit den Sprachen Deutsch, Romanisch und Italienisch zeigen sich die gesellschaftssprachlichen Strukturen je nach lokaler Sprachtradition und Sprachentwicklung sehr unterschiedlich. Entsprechend diesen Strukturen sind auch die institutionellen sprachlichen Gegebenheiten von einer Diversität geprägt, die sich in lokalen Vorgaben zur Sprachverwendung widerspiegeln aber auch in ihren damit einhergehenden Herausforderungen. Das Dissertationsprojekt untersucht die Praxis des Kindergartens im Hinblick auf den Umgang mit Zwei- und Mehrsprachigkeit. Mit einer ethnographisch angelegten Untersuchung werden in einer vergleichenden Perspektive die sprachlichen Praktiken von zwei sprachlich unterschiedlichen Kindergärten in den Blick genommen. Es handelt sich dabei um einen bilingualen Kindergarten in einer traditionell romanischsprachigen Region, die von einer starken Germanisierung betroffen ist, sowie um einen deutschsprachigen Kindergarten mit dem Spezifikum der Diglossie. Es hat sich gezeigt, dass die Sprachwahl im monolingualen Kindergarten adressatenorientiert erfolgt. Die dominierende Varietät ist der Dialekt, während Hochdeutsch nur in Situationen, in denen ein Kind mit Nicht-Deutsch als Erstsprache direkt beteiligt ist, gewählt wird. Auch im bilingualen Kindergarten konnte die adressatenorientierte Sprachwahl beobachtet werden, wobei dieser zusätzlich eine situationsorientierte Sprachwahl kennt. Unabhängig davon, ob die Sprachwahl adressatenorientiert oder situationsorientiert erfolgt, handelt es sich immer um eine Pädagogisierung des sprachlichen Differenzproblems. Die Pädagogisierung steht dabei immer in einem Spannungsverhältnis zwischen der Förderung der Kinder und ihrer Besonderung

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

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