Experiment
Genome scan at an average density of 20 cM was performed on a population of 203 NON/Lt x (NZO/HlLt x NON/Lt)F1 backcross male animals to identify loci associated with diabesity. The New Zealand Obese (NZO) strain develops early onset diabetes, and exhibits impaired glucose tolerance (IGT), insulin resistance and leptin resistance. The Nonobese Nondiabetic (NON) strain does not develop diabetes or obesity, exhibits normal leptin levels, but shows IGT and low insulin responses. A broad QTL was detected on mouse chromosome 1 from 8.3 cM - 43.1 cM and encompasses a variety of diabesity traits such as increased body weight, elevated plasma glucose levels, and early hyperinsulinemia. This locus, Dbsty1 (diabesity), appears to peak at approximately 21 cM near D1Mit123 with a LOD = 9.36 for body weight at 8 weeks of age. Dbsty2 is associated with adiposity index and maps to mouse Chromosome 5 at 45 cM with a LOD = 3.86 at D5Mit7. Dbsty3 maps to mouse Chromosome 12 from 45 cM - 53 cM with a peak LOD = 4.88 at D12Mit231 and is associated with body mass index, adiposity index, and leptin levels. Dbsty4 maps to mouse Chromosome 15 at approximately 49.6 cM with a peak LOD = 3.55 at D15Mit159 and is associated with plasma glucose. Inheritance of NZO-derived alleles at diabesity QTLS act to increase diabesity traits. Suggestive QTLs mapped to mouse Chromosome 3 for plasma insulin levels (LOD = 2.53 at D3Mit22), mouse Chromosome 6 for body weight, body mass index, plasma insulin, adiposity index, and leptin levels (peak LOD=3.42 at D6Mit123), mouse Chromosome 13 for body mass index (LOD = 2.03 at D13Mit53), and mouse Chromosome 18 for body mass index and adiposity index (LOD = 2.47 at D18Mit60). Complex interactions were detected among the diabesity QTLs as well as other loci. See article for details.
Analysis Tools