Genetic Dissection of Complex Genetic Factor Involved in NIDDM of OLETF Rat
The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, noninsulin-dependent diabetes mellitus (NIDDM) in humans. NIDDM in this rat model was shown to be regulated by multiple genes. We have identified 14 quantitative trait loci (QTLs) responsible for NIDDM (Nidd1-14/of) on chromosomes 1, 5, 7, 8, 9, 11, 12, 14, 16, and 17 by a whole genome search in 160 F2 progenies obtained by mating the OLETF and the F344 rats. Among these loci, two QTLs,Nidd1and2/of, were declared significant loci at a genome-wide level.Nidd3, 8, 9,and13/ofexhibited heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. We also found evidence for interaction (epistasis) betweenNidd1/ofandNidd2/of, betweenNidd1/ofandNidd10/of, betweenNidd2/ofandNidd8/of, and betweenNidd2/ofandNidd14/of. Furthermore,Nidd6and11/ofshowed linkage with body weight, andNidd1, 2, 8, 9, 10,and12/ofhad an interaction with body weight. These indicated that NIDDM in the OLETF would have a higher degree of genetic complexity. We suggest several interesting candidate genes located in rat genomic regions forNidd1-14/ofor the syntenic regions in human genome.