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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.
Pubmed ID: 29893858 RIS Download
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A commercial antibody supplier and provider of various services.
View all literature mentionsHarvester is a Web-based tool that bulk-collects bioinformatic data on human proteins from various databases and prediction servers. It is a meta search engine for gene and protein information. It searches 16 major databases and prediction servers and combines the results on pregenerated HTML pages. In this way Harvester can provide comprehensive gene-protein information from different servers in a convenient and fast manner. As full text meta search engine, similar to Google trade mark, Harvester allows screening of the whole genome proteome for current protein functions and predictions in a few seconds. With Harvester it is now possible to compare and check the quality of different database entries and prediction algorithms on a single page. Sponsors: This work has been supported by the BMBF with grants 01GR0101 and 01KW0013.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsSoftware program for mapping quantitative trait loci in experimental crosses. (entry from Genetic Analysis Software)
View all literature mentionsMus musculus with name DBA/2J from IMSR.
View all literature mentionslaboratory mouse with name 129P2/OlaHsd from MGI.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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