Document Detail

The importance of context to the genetic architecture of diabetes-related traits is revealed in a genome-wide scan of a LG/J × SM/J murine model.
MedLine Citation:
PMID:  21210123     Owner:  NLM     Status:  MEDLINE    
Variations in diabetic phenotypes are caused by complex interactions of genetic effects, environmental factors, and the interplay between the two. We tease apart these complex interactions by examining genome-wide genetic and epigenetic effects on diabetes-related traits among different sex, diet, and sex-by-diet cohorts in a Mus musculus model. We conducted a genome-wide scan for quantitative trait loci that affect serum glucose and insulin levels and response to glucose stress in an F(16) Advanced Intercross Line of the LG/J and SM/J intercross (Wustl:LG,SM-G16). Half of each sibship was fed a high-fat diet and half was fed a relatively low-fat diet. Context-dependent genetic (additive and dominance) and epigenetic (parent-of-origin imprinting) effects were characterized by partitioning animals into sex, diet, and sex-by-diet cohorts. We found that different cohorts often have unique genetic effects at the same loci, and that genetic signals can be masked or erroneously assigned to specific cohorts if they are not considered individually. Our data demonstrate that the effects of genes on complex trait variation are highly context-dependent and that the same genomic sequence can affect traits differently depending on an individual's sex and/or dietary environment. Our results have important implications for studies of complex traits in humans.
Heather A Lawson; Arthur Lee; Gloria L Fawcett; Bing Wang; L Susan Pletscher; Taylor J Maxwell; Thomas H Ehrich; Jane P Kenney-Hunt; Jason B Wolf; Clay F Semenkovich; James M Cheverud
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-01-06
Journal Detail:
Title:  Mammalian genome : official journal of the International Mammalian Genome Society     Volume:  22     ISSN:  1432-1777     ISO Abbreviation:  Mamm. Genome     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-14     Completed Date:  2011-06-20     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  9100916     Medline TA:  Mamm Genome     Country:  United States    
Other Details:
Languages:  eng     Pagination:  197-208     Citation Subset:  IM    
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MeSH Terms
Animals, Outbred Strains
Blood Glucose / analysis
Diabetes Mellitus, Type 2 / genetics*,  metabolism
Disease Models, Animal*
Genome-Wide Association Study*
Hybridization, Genetic
Insulin / blood
Mice* / genetics,  metabolism
Quantitative Trait Loci*
Grant Support
BB/C/516936//Biotechnology and Biological Sciences Research Council; P30 DK056341/DK/NIDDK NIH HHS; P30 DK056341-11/DK/NIDDK NIH HHS; R01 DK055736/DK/NIDDK NIH HHS; R01 DK055736/DK/NIDDK NIH HHS; R01 DK088083/DK/NIDDK NIH HHS; T32 HL091823/HL/NHLBI NIH HHS; T32-HL091823/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Blood Glucose; 0/Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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