@article{VogelKamitzHallahanetal.2018, author = {Vogel, Heike and Kamitz, Anne and Hallahan, Nicole and Lebek, Sandra and Schallschmidt, Tanja and Jonas, Wenke and J{\"a}hnert, Markus and Gottmann, Pascal and Zellner, Lisa and Kanzleiter, Timo and Damen, Mareike and Altenhofen, Delsi and Burkhardt, Ralph and Renner, Simone and Dahlhoff, Maik and Wolf, Eckhard and M{\"u}ller, Timo Dirk and Bl{\"u}her, Matthias and Joost, Hans-Georg and Chadt, Alexandra and Al-Hasani, Hadi and Sch{\"u}rmann, Annette}, title = {A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes}, series = {Human molecular genetics}, volume = {27}, journal = {Human molecular genetics}, number = {17}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0964-6906}, doi = {10.1093/hmg/ddy217}, pages = {3099 -- 3112}, year = {2018}, abstract = {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.}, language = {en} } @book{SchroederSchellhardtAkincietal.2015, author = {Schroeder, Christoph and Schellhardt, Christin and Akinci, Mehmet-Ali and Dollnick, Meral and Dux, Ginesa and G{\"u}lbeyaz, Esin I{\c{s}}{\i}l and J{\"a}hnert, Anne and Ko{\c{c}}-G{\"u}lt{\"u}rk, Ceren and K{\"u}hmstedt, Patrick and Kuhn, Florian and Mezger, Verena and Pfaff, Carol and {\"U}rkmez, Bet{\"u}l Sena}, title = {MULTILIT}, editor = {Schroeder, Christoph and Schellhardt, Christin}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-80390}, publisher = {Universit{\"a}t Potsdam}, year = {2015}, abstract = {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.}, language = {en} } @article{AgaBarfknechtHallahanGottmannetal.2020, author = {Aga-Barfknecht, Heja and Hallahan, Nicole and Gottmann, Pascal and J{\"a}hnert, Markus and Osburg, Sophie and Schulze, Gunnar and Kamitz, Anne and Arends, Danny and Brockmann, Gudrun and Schallschmidt, Tanja and Lebek, Sandra and Chadt, Alexandra and Al-Hasani, Hadi and Joost, Hans-Georg and Sch{\"u}rmann, Annette and Vogel, Heike}, title = {Identification of novel potential type 2 diabetes genes mediating beta-cell loss and hyperglycemia using positional cloning}, series = {Frontiers in genetics}, volume = {11}, journal = {Frontiers in genetics}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1664-8021}, doi = {10.3389/fgene.2020.567191}, pages = {11}, year = {2020}, abstract = {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.}, language = {en} }