Identification of epistatic interactions involved in non-insulin-dependentdiabetes mellitus in the Otsuka Long-Evans Tokushima Fatty rat

Citation
T. Yamada et al., Identification of epistatic interactions involved in non-insulin-dependentdiabetes mellitus in the Otsuka Long-Evans Tokushima Fatty rat, EXP ANIM, 50(2), 2001, pp. 115-123
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Animal Sciences
Journal title
EXPERIMENTAL ANIMALS
ISSN journal
1341-1357 → ACNP
Volume
50
Issue
2
Year of publication
2001
Pages
115 - 123
Database
ISI
SICI code
1341-1357(200104)50:2<115:IOEIII>2.0.ZU;2-6
Abstract
The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for ob ese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. Our pre sent investigation was designed to identify epistatic interactions influenc ing NIDDM by performing least squares analysis of variance of all pairs of informative markers in 160 F, progenies bred from an intercross of OLETF an d Fischer-344 rats. We identified four interactions between Nidd15/of (chro mosome 7) and Nidd16/of (chromosome 14), Nidd15/ of and Nidd17/of (chromoso me 15), Nidd16/of and Nidd18/of (chromosome 15), and Nidd16/of and Nidd19/o f (chromosome 17), which account for a total of similar to 40% of the genet ic variation of entire glucose levels after glucose challenge in the F,. Th e Nidd16/of locus, which is involved in three of four digenic interactions, and the Nidd19/of are likely to correspond to Nidd2/of and Nidd14/of, NIDD M loci previously identified in the F, by single-QTL model and multiple-QTL model, respectively, while Nidd15/of, Nidd17/of and Nidd18/of loci reflect novel NIDDM loci. An aberrant increase of the entire glucose level due to synergism occurs in the double OLETF homozygote genotype of Nidd15/of and N idd16/of, and of Nidd16/of and Nidd19/of, as well as in the OLETF homozygot e genotypes of Nidd15/ of and Nidd16/of, respectively, combined with the he terozygote genotypes of Nidd17/of and Nidd18/of. These findings demonstrate that inter-allelic interactions are likely to be an important component of NIDDM susceptibility.