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. (December 2017)

• Record Type: Journal Article
• Authors: Vogel, Heike; Jähnert, Markus; Stadion, Mandy; Matzke, Daniela; Scherneck, Stephan; Schürmann, Annette
• Is Part Of: BMC genomics. Volume 18:Number 1(2017)
• Page Start: 1
• Page End: 9
• Publication Date: 2017-12
• Subjects: BAC library -- Gene cluster -- Deletion -- Obesity; Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/s12864-017-3552-6
• Languages: English
• ISSNs: 1471-2164

Abstract

Abstract Background 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. Results In the current study we generated a BAC library of the obese-prone NZO strain to clarify the genomic alteration within the gene clusterIfi200 on chr.1 includingIfi202b, 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 theIfi200 gene family which also includes the original first exon and 5′-regulatory parts of theIfi202b 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. Conclusions Our data reveal the reconstruction of a complex genomic region on mouse chr.1 resulting from deletions and duplications ofIfi200 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.