TY - JOUR A1 - Vogel, Heike A1 - Kamitz, Anne A1 - Hallahan, Nicole A1 - Lebek, Sandra A1 - Schallschmidt, Tanja A1 - Jonas, Wenke A1 - Jähnert, Markus A1 - Gottmann, Pascal A1 - Zellner, Lisa A1 - Kanzleiter, Timo A1 - Damen, Mareike A1 - Altenhofen, Delsi A1 - Burkhardt, Ralph A1 - Renner, Simone A1 - Dahlhoff, Maik A1 - Wolf, Eckhard A1 - Müller, Timo Dirk A1 - Blüher, Matthias A1 - Joost, Hans-Georg A1 - Chadt, Alexandra A1 - Al-Hasani, Hadi A1 - Schürmann, Annette T1 - A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes JF - Human molecular genetics N2 - To explore the genetic determinants of obesity and Type 2 diabetes (T2D), the German Center for Diabetes Research (DZD) conducted crossbreedings of the obese and diabetes-prone New Zealand Obese mouse strain with four different lean strains (B6, DBA, C3H, 129P2) that vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 quantitative trait loci (QTL) for obesity, 190 QTL for diabetes-related traits and 100 QTL for plasma metabolites in the out-cross populations. A computational framework was developed that allowed to refine critical regions and to nominate a small number of candidate genes by integrating reciprocal haplotype mapping and transcriptome data. The efficiency of the complex procedure was demonstrated for one obesity QTL. The genomic interval of 35 Mb with 502 annotated candidate genes was narrowed down to six candidates. Accordingly, congenic mice retained the obesity phenotype owing to an interval that contains three of the six candidate genes. Among these the phospholipase PLA2G4A exhibited an elevated expression in adipose tissue of obese human subjects and is therefore a critical regulator of the obesity locus. Together, our broad and complex approach demonstrates that combined- and comparative-cross analysis exhibits improved mapping resolution and represents a valid tool for the identification of disease genes. Y1 - 2018 U6 - https://doi.org/10.1093/hmg/ddy217 SN - 0964-6906 SN - 1460-2083 VL - 27 IS - 17 SP - 3099 EP - 3112 PB - Oxford Univ. Press CY - Oxford ER - TY - BOOK A1 - Schroeder, Christoph A1 - Schellhardt, Christin A1 - Akinci, Mehmet-Ali A1 - Dollnick, Meral A1 - Dux, Ginesa A1 - Gülbeyaz, Esin Işıl A1 - Jähnert, Anne A1 - Koç-Gültürk, Ceren A1 - Kühmstedt, Patrick A1 - Kuhn, Florian A1 - Mezger, Verena A1 - Pfaff, Carol A1 - Ürkmez, Betül Sena ED - Schroeder, Christoph ED - Schellhardt, Christin T1 - MULTILIT BT - manual, criteria of transcription and analysis for German, Turkish and English N2 - This paper presents an overview of the linguistic analyses developed in the MULTILIT project and the processing of the oral and written texts collected. The project investigates the language abilities of multilingual children and adolescents, in particular, those who have Turkish and/or Kurdish as a mother tongue. A further aim of the project is to examine from a psycholinguistic and sociolinguistic perspective the extent to which competence in academic registers is achieved on the basis of the languages spoken by the children, including the language(s) spoken at the home, the language of the country of residence and the first foreign language. To be able to examine these questions using corpus linguistic parameters, we created categories of analysis in MULTILIT. The data collection comprises texts from bilingual and monolingual children and adolescents in Germany in their first language Turkish, their second language German und their foreign language English. Pupils aged between nine and twenty years of age produced monologue oral and written texts in the two genres of narrative and discursive. On the basis of these samples, we examine linguistic features such as lexical expression (lexical density, lexical diversity), syntactic complexity (syntactic and discursive packaging) as well as phonology in the oral texts and orthography in the written texts, with the aim of investigating the pupils’ growing mastery of these features in academic and informal registers. To this end the raw data have been transcribed by the use of transcription conventions developed especially for the needs of the MULTILIT data. They are based on the commonly used HIAT and GAT transcription conventions and supplemented with conventions that provide additional information such as features at the graphic level. The categories of analysis comprise a large number of linguistic categories such as word classes, syntax, noun phrase complexity, complex verbal morphology, direct speech and text structures. We also annotate errors and norm deviations at a wide range of levels (orthographic, morphological, lexical, syntactic and textual). In view of the different language systems, these criteria are considered separately for all languages investigated in the project. N2 - Die vorliegende Arbeit stellt eine Übersicht der linguistischen Analysen dar, die im Rahmen des MULTILIT Projektes entwickelt wurden. Darüber hinaus wird die Aufbereitung der erhobenen mündlichen und schriftlichen Texte vorgestellt. Das Projekt betrachtet die sprachlichen Fähigkeiten multilingualer Kinder und Jugendlicher, insbesondere mit der Muttersprache Türkisch und/oder Kurdisch. Ein weiteres Ziel des Projektes ist die Untersuchung der Entwicklung eines akademischen Registers der Sprachen der Kinder, d.h. der zu Hause gesprochenen Sprache(n), der Sprache des Aufenthaltslandes und der ersten Fremdsprache unter psycholinguistischen und soziolinguistischen Gesichtspunkten. Zur Untersuchung dieser Forschungsfragen unter korpuslinguistischen Parametern wurden in MULTILIT Analysekriterien entwickelt. Die Datenerhebung umfasst Texte bilingualer und monolingualer Kinder und Jugendlicher in ihrer Erstsprache Türkisch, ihrer Zweitsprache Deutsch sowie ihrer ersten Fremdsprache Englisch. Schüler im Alter von 9 bis 20 Jahren haben sowohl mündliche als auch schriftliche monologische Texte in zwei Genres produziert – erzählend und erörternd. Basierend auf diese Daten untersuchen wir linguistische Bereiche wie lexikalischer Ausdruck (lexikalische Dichte, lexikalische Vielfalt), syntaktische Komplexität (syntaktische und diskursive Verdichtung) sowie Phonologie in den mündlichen Texten und Orthographie in den schriftlichen Texten mit dem Ziel, die wachsende Beherrschung dieser Bereiche in akademischen und informellen Registern durch die Schüler zu untersuchen. Dafür wurden die Rohdaten mit Transkriptionskonventionen verarbeitet, die speziell auf die Bedürfnisse des MULTILIT Projektes zugeschnitten sind. Sie basieren auf den weit verbreiteten Transkriptionskonventionen HIAT und GAT und wurden durch Konventionen erweitert, die zusätzliche Informationen, beispielsweise auf graphischer Ebene, festhalten. Die Analysekategorien umfassen zahlreiche linguistische Kategorien, wie Wortarten, Syntax, Nominalphrasenkomplexität, komplexe Verbalmorphologie, direkte Rede und Textstrukturen. Außerdem annotieren wir Fehler und Normabweichungen auf allen zahlreichen Ebenen (orthographisch, morphologisch, lexikalisch, syntaktisch und textuell). Aufgrund der verschiedenen Sprachsysteme werden diese Analysekategorien für alle im Projekt untersuchten Sprachen gesondert betrachtet. KW - bilingualism KW - child KW - German KW - German lessons KW - migration KW - multilingualism KW - second language KW - Turkish KW - writing ability KW - written language acquisition KW - DaZ KW - Deutsch KW - Deutschunterricht KW - Kind KW - Mehrsprachigkeit KW - Schreiben KW - Schreibfähigkeit KW - Schriftsprache KW - Schriftspracherwerb KW - Sprachförderung KW - Türkisch KW - Zweitsprache Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-80390 ER - TY - JOUR A1 - Aga-Barfknecht, Heja A1 - Hallahan, Nicole A1 - Gottmann, Pascal A1 - Jähnert, Markus A1 - Osburg, Sophie A1 - Schulze, Gunnar A1 - Kamitz, Anne A1 - Arends, Danny A1 - Brockmann, Gudrun A1 - Schallschmidt, Tanja A1 - Lebek, Sandra A1 - Chadt, Alexandra A1 - Al-Hasani, Hadi A1 - Joost, Hans-Georg A1 - Schürmann, Annette A1 - Vogel, Heike T1 - Identification of novel potential type 2 diabetes genes mediating beta-cell loss and hyperglycemia using positional cloning JF - Frontiers in genetics N2 - Type 2 diabetes (T2D) is a complex metabolic disease regulated by an interaction of genetic predisposition and environmental factors. To understand the genetic contribution in the development of diabetes, mice varying in their disease susceptibility were crossed with the obese and diabetes-prone New Zealand obese (NZO) mouse. Subsequent whole-genome sequence scans revealed one major quantitative trait loci (QTL),Nidd/DBAon chromosome 4, linked to elevated blood glucose and reduced plasma insulin and low levels of pancreatic insulin. Phenotypical characterization of congenic mice carrying 13.6 Mbp of the critical fragment of DBA mice displayed severe hyperglycemia and impaired glucose clearance at week 10, decreased glucose response in week 13, and loss of beta-cells and pancreatic insulin in week 16. To identify the responsible gene variant(s), further congenic mice were generated and phenotyped, which resulted in a fragment of 3.3 Mbp that was sufficient to induce hyperglycemia. By combining transcriptome analysis and haplotype mapping, the number of putative responsible variant(s) was narrowed from initial 284 to 18 genes, including gene models and non-coding RNAs. Consideration of haplotype blocks reduced the number of candidate genes to four (Kti12,Osbpl9,Ttc39a, andCalr4) as potential T2D candidates as they display a differential expression in pancreatic islets and/or sequence variation. In conclusion, the integration of comparative analysis of multiple inbred populations such as haplotype mapping, transcriptomics, and sequence data substantially improved the mapping resolution of the diabetes QTLNidd/DBA. Future studies are necessary to understand the exact role of the different candidates in beta-cell function and their contribution in maintaining glycemic control. KW - type 2 diabetes KW - beta-cell loss KW - insulin KW - positional cloning KW - transcriptomics KW - haplotype Y1 - 2020 U6 - https://doi.org/10.3389/fgene.2020.567191 SN - 1664-8021 VL - 11 PB - Frontiers Media CY - Lausanne ER -