RGD Reference Report - Identification of epistatic interactions involved in non-insulin-dependent diabetes mellitus in the Otsuka Long-Evans Tokushima Fatty rat. - Rat Genome Database

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

Authors: Yamada, T  Miyake, T  Sugiura, K  Narita, A  Wei, K  Wei, S  Moralejo, DH  Ogino, T  Gaillard, C  Sasaki, Y  Matsumoto, K 
Citation: Yamada T, etal., Exp Anim 2001 Apr;50(2):115-23.
RGD ID: 619670
Pubmed: PMID:11381614   (View Abstract at PubMed)

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 investigation was designed to identify epistatic interactions influencing NIDDM by performing least squares analysis of variance of all pairs of informative markers in 160 F2 progenies bred from an intercross of OLETF and Fischer-344 rats. We identified four interactions between Nidd15/of (chromosome 7) and Nidd16/of (chromosome 14), Nidd15/of and Nidd17/of (chromosome 15), Nidd16/of and Nidd18/of (chromosome 15), and Nidd16/of and Nidd19/of (chromosome 17), which account for a total of approximately 40% of the genetic variation of entire glucose levels after glucose challenge in the F2. The 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, NIDDM loci previously identified in the F2 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 Nidd16/of, and of Nidd16/of and Nidd19/of, as well as in the OLETF homozygote genotypes of Nidd15/of and Nidd16/of, respectively, combined with the heterozygote genotypes of Nidd17/of and Nidd18/of. These findings demonstrate that inter-allelic interactions are likely to be an important component of NIDDM susceptibility.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glucose intolerance  IDA 619670; 619670; 619670; 619670; 619670 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
impaired glucose tolerance  QTM 619670; 619670; 619670; 619670; 619670 RGD 
Objects Annotated

Niddm52  (Non-insulin dependent diabetes mellitus QTL 52)
Niddm53  (Non-insulin dependent diabetes mellitus QTL 53)
Niddm54  (Non-insulin dependent diabetes mellitus QTL 54)
Niddm55  (Non-insulin dependent diabetes mellitus QTL 55)
Niddm56  (Non-insulin dependent diabetes mellitus QTL 56)

F344/DuCrlCrlj  (NA)
OLETF/Got  (Otsuka Long Evans Tokushima)

Additional Information