Your browser doesn't support javascript.
loading
A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes.
Vogel, Heike; Kamitz, Anne; Hallahan, Nicole; Lebek, Sandra; Schallschmidt, Tanja; Jonas, Wenke; Jähnert, Markus; Gottmann, Pascal; Zellner, Lisa; Kanzleiter, Timo; Damen, Mareike; Altenhofen, Delsi; Burkhardt, Ralph; Renner, Simone; Dahlhoff, Maik; Wolf, Eckhard; Müller, Timo D; Blüher, Matthias; Joost, Hans-Georg; Chadt, Alexandra; Al-Hasani, Hadi; Schürmann, Annette.
Afiliación
  • Vogel H; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal D-14558, Germany.
  • Kamitz A; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Hallahan N; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal D-14558, Germany.
  • Lebek S; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Schallschmidt T; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal D-14558, Germany.
  • Jonas W; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Jähnert M; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Gottmann P; Medical Faculty, Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center (DDZ), Heinrich Heine University, Düsseldorf D-40225, Germany.
  • Zellner L; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Kanzleiter T; Medical Faculty, Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center (DDZ), Heinrich Heine University, Düsseldorf D-40225, Germany.
  • Damen M; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal D-14558, Germany.
  • Altenhofen D; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Burkhardt R; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal D-14558, Germany.
  • Renner S; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Dahlhoff M; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal D-14558, Germany.
  • Wolf E; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Müller TD; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal D-14558, Germany.
  • Blüher M; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Joost HG; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal D-14558, Germany.
  • Chadt A; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Al-Hasani H; German Center for Diabetes Research (DZD), München-Neuherberg D-85764, Germany.
  • Schürmann A; Medical Faculty, Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center (DDZ), Heinrich Heine University, Düsseldorf D-40225, Germany.
Hum Mol Genet ; 27(17): 3099-3112, 2018 09 01.
Article en En | MEDLINE | ID: mdl-29893858
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 outcross 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.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores / Biología Computacional / Polimorfismo de Nucleótido Simple / Sitios de Carácter Cuantitativo / Diabetes Mellitus Tipo 2 / Fosfolipasas A2 Grupo IV / Obesidad Tipo de estudio: Prognostic_studies Límite: Adolescent / Adult / Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2018 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores / Biología Computacional / Polimorfismo de Nucleótido Simple / Sitios de Carácter Cuantitativo / Diabetes Mellitus Tipo 2 / Fosfolipasas A2 Grupo IV / Obesidad Tipo de estudio: Prognostic_studies Límite: Adolescent / Adult / Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Hum Mol Genet Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2018 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido