Document Detail


Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice.
MedLine Citation:
PMID:  20858711     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Stressful environmental factors, such as a high-fat diet, can induce responses in the expression of genes that act to maintain physiological homeostasis. We observed variation in plasma concentrations of high-density lipoprotein (HDL) cholesterol across inbred mouse strains in response to high dietary fat intake. Several strains, including C57BL/6J, have stable levels of plasma HDL independent of diet, whereas other strains, including DBA2/J, show marked changes in plasma HDL. To explore this phenomenon further, we used publicly available data from a C57BL/6J × DBA/2J intercross to identify genetic factors that associate with HDL under high-fat diet conditions. Our analysis identified an epistatic interaction that plays a role in the buffering of HDL levels in C57BL/6J mice, and we have identified Arl4d as a candidate gene that mediates this effect. Structural modeling further elucidates the interaction of genetic factors that contribute to the robustness of HDL in response to high-fat diet in the C57BL/6J strain.
Authors:
Renhua H Li; Gary A Churchill
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-21
Journal Detail:
Title:  Physiological genomics     Volume:  42A     ISSN:  1531-2267     ISO Abbreviation:  Physiol. Genomics     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2011-02-28     Revised Date:  2011-12-21    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  228-34     Citation Subset:  IM    
Affiliation:
The Jackson Laboratory, Bar Harbor, Maine, USA. lir3@niddk.nih.gov
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MeSH Terms
Descriptor/Qualifier:
ADP-Ribosylation Factors / genetics,  metabolism*
Animals
Cholesterol, HDL / blood*
Crosses, Genetic
Dietary Fats / metabolism*
Epistasis, Genetic*
Female
Lipoproteins, HDL / genetics*
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Species Specificity
Grant Support
ID/Acronym/Agency:
GM-070683/GM/NIGMS NIH HHS; GM-076468/GM/NIGMS NIH HHS; R01 GM070683-07/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Cholesterol, HDL; 0/Dietary Fats; 0/Lipoproteins, HDL; EC 3.6.5.2/ADP-Ribosylation Factors; EC 3.6.5.2/Arl4D protein, mouse

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


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