International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E2/57 Identification of Epistatic Interactions Involved in Non-Insulin-Dependent Diabetes Mellitus in the Otsuka Long-Evans Tokushima Fatty Rat

Takahisa Yamada1,2, Takeshi Miyake2, Yoshiyuki Sasaki2, Hiroyuki Kose1 and Kozo Matsumoto1. 1Institute for Animal Experimentation, University of Tokushima School of Medicine, 2Laboratory of Animal Breeding and Genetics, Graduate School of Agriculture, Kyoto University

Epistatic interaction results in the case when the combined effect of two or more genes on a phenotype could not have been predicted as the sum of their sepatate effects. It is clear from crosses involving a strain of model organism susceptible to a certain disease with different non-susceptible strains that the genes of the susceptible strain show differential effects with the different background strain genomes, reflecting gene to gene interaction effects.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. Our present study was to identify epistatic interactions influencing NIDDM by performing analysis of variance of informative markers in 160 F2 progenies bred from the OLETF rat. We have identified four interactions between loci on Chr 7 and 14, loci on Chr 7 and 15, loci on Chr 14 and 15, and loci on Chr 14 and 17, which account for a total of about 40% of the genetic variation of entire glucose levels after glucose challenge in the F2. The Chr 14 locus, which is involved in three of four digenic interactions, is likely to correspond to one of NIDDM loci previously identified in the F2 by single-QTL model, while no other loci reflect the NIDDM loci. An aberrant increase of the entire glucose levels due to synergism occurs in the double OLETF homozygote genotype at two interactions, as well as in the OLETF homozygote genotype combined with the heterozygote genotype at other two interactions. These findings demonstrate that inter-allelic interactions are likely to be an important component of NIDDM susceptibility.

 


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