Faculty Collaboration Database

Mapping and characterization of quantitative trait loci for non-insulin-dependent diabetes mellitus with an improved genetic map in the Otsuka Long-Evans Tokushima fatty rat. Mamm Genome 1999 Mar;10(3):249-58

Date

03/02/1999

Pubmed ID

10051320

DOI

10.1007/s003359900982

Scopus ID

2-s2.0-0032805994 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, non-insulin-dependent diabetes mellitus (NIDDM) in humans. We have previously reported four quantitative trait loci (QTLs) responsible for NIDDM on Chromosomes (Chrs) 7, 14, 8, and 11 (Nidd1-4/of for Non-insulin-dependent diabetes1-4/oletf) by a whole-genome search in 160 F2 progenies obtained by mating the OLETF and the Fischer-344 (F344) rats. Our present investigation was designed to identify and characterize novel QTLs affecting NIDDM by performing a genome-wide linkage analysis of genes for glucose levels and body weight and analysis for gene-to-gene and gene-to-body-weight interactions on an improved genetic map with a set of 382 informative markers in the 160 F2 progenies. We have identified seven novel QTLs on rat Chrs 1 (Nidd5 and 6/of), 5 (Nidd7/of), 9 (Nidd8/of), 12 (Nidd9/of), 14 (Nidd10/of) and 16 (Nidd11/of) which, together with the Nidd1-4/of, account for a total of approximately 60% and approximately 75% of the genetic variance of the fasting and postprandial glucose levels, respectively, in the F2. While the OLETF allele corresponds with increased glucose levels as expected for the novel QTLs except Nidd8 and 9/of, the Nidd8 and 9/of exhibit heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. There are epistatic interactions between Nidd1 and 10/of and between Nidd2 and 8/of. Additionally, our results indicated that the Nidd6 and 11/of could also contribute to an increase of body weight, and that the other five QTLs could show no linkage with body weight, but Nidd8,9, and 10/of have an interaction with body weight.

Author List

Wei S, Wei K, Moralejo DH, Ogino T, Koike G, Jacob HJ, Sugiura K, Sasaki Y, Yamada T, Matsumoto K

MESH terms used to index this publication - Major topics in bold

Animals
Body Weight
Chromosome Mapping
Crosses, Genetic
Diabetes Mellitus, Type 2
Genotype
Homozygote
Lod Score
Quantitative Trait, Heritable
Rats
Rats, Inbred F344
Rats, Inbred OLETF