Experiment
A Genome wide scan was performed on 160 (BTBR x C57BL/6J) F2-ob/ob intercross animals, using 99 informative markers at an average spacing of 16 cM, to identify loci affecting diabetes in obese animals. Neither parental strain BTBR nor C57BL/6J exhibit diabetes or obesity phenotypes, but lean male (BTBR x C57BL/6J) F1 hybrid animals develop severe hyperglycemia indicating the existence of diabetes susceptibility alleles in BTBR and C57BL/6J genetic backgrounds. Initial mapping indicate that mouse Chromosomes 2, 16 and 19 were involved in diabetic phenotypes. LOD values derived from multitrait composite interval mapping were used to further refine the map locations.
A locus associated with 8- and 10-week glucose and insulin levels, T2dm1 (type 2 diabetes mellitus 1), mapped to mouse Chromosome 16 with a LOD > 4.0 at D16Mit12. BTBR-derived alleles are dominant to C57BL/6J-derived alleles at T2dm1. T2dm2, a locus associated with 10-week insulin levels, mapped to mouse Chromosome 19 with a LOD >7.5 atD19Mit35. BTBR-derived alleles increase insulin levels by 38% in a dominant fashion at T2dm2. T2dm2 is also suggestively associated with glucose levels (LOD = 3.79, with C57BL/6J-derived alleles increasing glucose levels). T2dm3 mapped to mouse Chromosome 2 with a peak LOD score of >6.5 between D2Mit274 and D2Mit106 in association with insulin levels. T2dm3 appears to exhibit additive inheritance and maps near the agouti (a) and mahogany (Atrn, previously mg) genes. A suggestive locus for 8-week glucoselevels mapped to mouse Chromosome 4 (LOD = 3) and a suggestive locus for 8- and 10-week insulin levels mapped to distal mouse Chromosome 5 (LOD = 3.2 and 2.7, respectively).
Analysis Tools