Oral Presentation The Annual Scientific Meeting of the Australian Diabetes Society and the Australian Diabetes Educators Association 2013

 Identifying Type 2 Diabetes Susceptibility Loci Using The "Gene Mine" (#176)

Salvatore P Mangiafico 1 , Chieh-Hsin Yang 1 , Fabio Manippa 1 , Sof Andrikopoulos 1 , Grant Morahan 2
  1. Department of Medicine, The University of Melbourne, Austin Health, Melbourne, Victoria, Australia
  2. Centre for Diabetes Research, University of Western Australia, Perth, Western Australia, Australia

The "Gene Mine" or Collaborative Cross is a next-generation genetic resource developed to simplify discovery of genes controlling complex genetic traits. It consists of hundreds of inbred mouse strains descended from eight genetically diverse founders. To identify genetic loci associated with Type 2 diabetes susceptibility, we characterised basal blood glucose and insulin sensitivity in 50 Collaborative Cross strains using an insulin tolerance test (0.75IU/kg) followed by genetic linkage analysis using HAPPY modified for the Collaborative Cross. Strains with a high basal blood glucose level and thus strong genetic predisposition to β-cell dysfunction were subjected to oral and intravenous glucose tolerance tests (OGTT 2g/kg and IVGTT 1g/kg). Linkage analysis localised several hotspots for diabetes susceptibility with 90% confidence. One locus was mapped to chromosome 8 with genome-wide significance at 95% confidence (F statistic p<0.05). Glucose tolerance tests showed several strains had abnormal glucose tolerance. Two of these strains provide novel mouse models of Type 2 Diabetes susceptibility with reduced insulin secretion.  Our results validate the utility of the "Gene Mine" as a powerful genetic resource for the identification of Diabetes susceptibility loci and for the generation and characterisation of novel mouse models for the study of Type 2 Diabetes

  1. Morahan G, Balmer L, Monley D. Establishment of "The Gene Mine": a resource for rapid identification of complex trait genes. Mamm Genome. 2008 Jun;19(6):390-3