title: A vast genomic deletion in the C56BL/6 genome affects different genes within the Ifi200 cluster on chromosome 1 and mediates obesity and insulin resistance.
abstract: Obesity, the excessive accumulation of body fat, is a highly heritable and genetically heterogeneous disorder. The complex, polygenic basis for the disease consisting of a network of different gene variants is still not completely known.
  
  
  
  In the current study we generated a BAC library of the obese-prone NZO strain to clarify the genomic alteration within the gene cluster Ifi200 on chr.1 including Ifi202b, an obesity gene that is in contrast to NZO not expressed in the lean B6 mouse. With the PacBio sequencing data of NZO BAC clones we identified a deletion spanning approximately 261.8 kb in the B6 reference genome. The deletion affects different members of the Ifi200 gene family which also includes the original first exon and 5'-regulatory parts of the Ifi202b gene and suggests to be the relevant cause of its expression deficiency in B6. In addition, the generation and characterization of congenic mice carrying the critical fragment on the B6 background demonstrate its crucial role for obesity and insulin resistance.
  
  
  
  Our data reveal the reconstruction of a complex genomic region on mouse chr.1 resulting from deletions and duplications of Ifi200 genes and suggest to be relevant for the development of obesity. The results further demonstrate the complexity of the disease and highlight the importance for studying rare genetic variants as they can be causal for large effects.
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert Allee 114-116, D-14558, Nuthetal, Germany.|German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, München-Neuherberg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Vogel
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert Allee 114-116, D-14558, Nuthetal, Germany.|German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, München-Neuherberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Jähnert
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert Allee 114-116, D-14558, Nuthetal, Germany.|German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, München-Neuherberg, Germany.
authors.forename: Mandy
authors.initials: M
authors.lastname: Stadion
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert Allee 114-116, D-14558, Nuthetal, Germany.|German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, München-Neuherberg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Matzke
authors.affiliation: Institute of Pharmacology and Toxicology, University of Braunschweig, Mendelssohnstr. 1, 38106, Braunschweig, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Scherneck
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert Allee 114-116, D-14558, Nuthetal, Germany. schuermann@dife.de.|German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, 85764, München-Neuherberg, Germany. schuermann@dife.de.
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
mesh_terms: D000818:Animals; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000235:genetics*; D015723:Gene Library; D023281:Genomics; D060005:Genotyping Techniques; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
keywords: BAC library; Deletion; Gene cluster; Obesity