Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Rapid Identification of Obesity and Type 2 Diabetes Susceptibility Genes Using The ‘Gene Mine’  (#166)

Salvatore P Mangiafico 1 , Ramesh Ram 2 , Fabio Manippa 1 , Chieh-Hsin Yang 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, Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia

The ‘Gene Mine’, is a next-generation genetic resource designed to simplify discovery of genes controlling complex genetic disorders such as obesity and Type 2 Diabetes (T2D).  It consists of a large number of inbred mouse strains descended from 8 genetically-diverse founders, including the New Zealand Obese (NZO), a polygenic model of obesity and T2D.  To identify genes associated with susceptibility to obesity and T2D, we measured body weight, blood glucose and insulin sensitivity using an insulin tolerance test (0.75IU/kg Actrapid, IP) in over 50 Gene Mine strains followed by gene mapping studies using specially developed software.  We mapped several genetic loci significantly associated with the development of obesity, insulin resistance and non-fasting hyperglycaemia with sufficient resolution to identify single gene candidates for some loci.  Two of these candidates encode proteins which are being exploited for the treatment of human obesity and/or T2D.  We also discovered a previously unrecognised gene which may contribute to the development of obesity in the NZO mouse.  Our results provide clear evidence that the Gene Mine is a powerful genetic resource for precise, rapid identification of single genes contributing to complex metabolic disorders such as obesity and T2D.