| 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. | |
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MedLine Citation:
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PMID: 21210123 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-01-06 |
Journal Detail:
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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:
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Created Date: 2011-03-14 Completed Date: 2011-06-20 Revised Date: 2012-02-14 |
Medline Journal Info:
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Nlm Unique ID: 9100916 Medline TA: Mamm Genome Country: United States |
Other Details:
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Languages: eng Pagination: 197-208 Citation Subset: IM |
Affiliation:
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Department of Anatomy & Neurobiology, Washington University School of Medicine, 3820 North Building, Campus Box 8108, St. Louis, MO 63110, USA. lawsonh@pcg.wustl.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Outbred Strains Blood Glucose / analysis Diabetes Mellitus, Type 2 / genetics*, metabolism Disease Models, Animal* Female Genome-Wide Association Study* Humans Hybridization, Genetic Insulin / blood Male Mice* / genetics, metabolism Quantitative Trait Loci* |
| Grant Support | |
ID/Acronym/Agency:
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BB/C/516936//Biotechnology and Biological Sciences Research Council; P30 DK056341-11/DK/NIDDK NIH HHS; R01 DK055736/DK/NIDDK NIH HHS; R01 DK088083-03/DK/NIDDK NIH HHS; T32-HL091823/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Insulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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