1. Genomics. 1997 May 1;41(3):332-44.
Genetic modifiers of Leprfa associated with variability in insulin production and
susceptibility to NIDDM.
Chung WK(1), Zheng M, Chua M, Kershaw E, Power-Kehoe L, Tsuji M, Wu-Peng XS,
Williams J, Chua SC Jr, Leibel RL.
Author information:
(1)Laboratory of Human Behavior and Metabolism, Rockefeller University, New York,
New York 10021, USA.
In an attempt to identify the genetic basis for susceptibility to
non-insulin-dependent diabetes mellitus within the context of obesity, we
generated 401 genetically obese Leprfa/Leprfa F2 WKY13M intercross rats that
demonstrated wide variation in multiple phenotypic measures related to diabetes,
including plasma glucose concentration, percentage of glycosylated hemoglobin,
plasma insulin concentration, and pancreatic islet morphology. Using selective
genotyping genome scanning approaches, we have identified three quantitative
trait loci (QTLs) on Chr. 1 (LOD 7.1 for pancreatic morpholology), Chr. 12 (LOD
5.1 for body mass index and LOD 3.4 for plasma glucose concentration), and Chr.
16 (P < 0.001 for genotype effect on plasma glucose concentration). The obese F2
progeny demonstrated sexual dimorphism for these traits, with increased diabetes
susceptibility in the males appearing at approximately 6 weeks of age, as sexual
maturation occurred. For each of the QTLs, the linked phenotypes demonstrated
sexual dimorphism (more severe affection in males). The QTL on Chr. 1 maps to a
region vicinal to that previously linked to adiposity in studies of diabetes
susceptibility in the nonobese Goto-Kakizaki rat, which is genetically closely
related to the Wistar counterstrain we employed. Several candidate genes,
including tubby (tub), multigenic obesity 1 (Mob1), adult obesity and diabetes
(Ad), and insulin-like growth factor-2 (Igf2), map to murine regions homologous
to the QTL region identified on rat Chr. 1.
PMID: 9169130 [PubMed - indexed for MEDLINE]
PUBMED: 9169130
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