Diet-dependent genetic and genomic imprinting effects on obesity in mice.

作者: James M. Cheverud , Heather A. Lawson , Gloria L. Fawcett , Bing Wang , L. Susan Pletscher

DOI: 10.1038/OBY.2010.141

关键词:

摘要: Although the current obesity epidemic is of environmental origin, there substantial genetic variation in individual response to an obesogenic environment. In this study, we perform a genome-wide scan for quantitative trait loci (QTLs) affecting per se, or obese high-fat diet mice from LG/J by SM/J Advanced Intercross (AI) Line (Wustl:LG,SM-G16). A total 1,002 animals 78 F₁₆ full sibships were weaned at 3 weeks age and half each litter placed on high- low-fat diets. Animals remained until 20 when they necropsied weights reproductive, kidney, mesenteric, inguinal fat depots recorded. Effects these phenotypes, along with depot weight carcass necropsy, mapped across genome using 1,402 autosomal single-nucleotide polymorphism (SNP) markers. Haplotypes reconstructed additive, dominance, imprinting genotype scores derived every 1 cM map. Analysis was performed mixed model scores, their interactions sex, diet, sex-by-diet as fixed effects family its interaction random effects. We discovered 95 trait-specific QTLs mapping 40 locations. Most had additive dominance occurring two-thirds loci. Nearly locus interacted sex and/or important ways demonstrating that gene are primarily context dependent, changing depending diet.

参考文章(44)
JAMES M. CHEVERUD, L. SUSAN PLETSCHER, TY T. VAUGHN, BESS MARSHALL, Differential response to dietary fat in large (LG/J) and small (SM/J) inbred mouse strains Physiological Genomics. ,vol. 1, pp. 33- 39 ,(1999) , 10.1152/PHYSIOLGENOMICS.1999.1.1.33
Margalida Frontera, Benjamin Dickins, Antonius Plagge, Gavin Kelsey, Imprinted genes, postnatal adaptations and enduring effects on energy homeostasis Advances in Experimental Medicine and Biology. ,vol. 626, pp. 41- 61 ,(2008) , 10.1007/978-0-387-77576-0_4
Karl W Broman, Saunak Sen, None, A Guide to QTL Mapping with R/qtl ,(2009)
JING LI, TAO JIANG, Efficient inference of haplotypes from genotypes on a pedigree. Journal of Bioinformatics and Computational Biology. ,vol. 1, pp. 41- 69 ,(2003) , 10.1142/S0219720003000204
Boyd A Swinburn, Gary Sacks, Sing Kai Lo, Klaas R Westerterp, Elaine C Rush, Michael Rosenbaum, Amy Luke, Dale A Schoeller, James P DeLany, Nancy F Butte, Eric Ravussin, Estimating the changes in energy flux that characterize the rise in obesity prevalence The American Journal of Clinical Nutrition. ,vol. 89, pp. 1723- 1728 ,(2009) , 10.3945/AJCN.2008.27061
Randy L. Jirtle, Michael K. Skinner, Environmental epigenomics and disease susceptibility Nature Reviews Genetics. ,vol. 8, pp. 253- 262 ,(2007) , 10.1038/NRG2045
Clifton Bogardus, Missing heritability and GWAS utility. Obesity. ,vol. 17, pp. 209- 210 ,(2009) , 10.1038/OBY.2008.613
Thomas H. Ehrich, Jane P. Kenney, Ty T. Vaughn, L. Susan Pletscher, James M. Cheverud, Diet, Obesity, and Hyperglycemia in LG/J and SM/J Mice Obesity Research. ,vol. 11, pp. 1400- 1410 ,(2003) , 10.1038/OBY.2003.189
Jason B. Wolf, James M. Cheverud, A framework for detecting and characterizing genetic background-dependent imprinting effects Mammalian Genome. ,vol. 20, pp. 681- 698 ,(2009) , 10.1007/S00335-009-9209-2
THOMAS H. EHRICH, JANE P. KENNEY-HUNT, L. SUSAN PLETSCHER, JAMES M. CHEVERUD, Genetic variation and correlation of dietary response in an advanced intercross mouse line produced from two divergent growth lines. Genetics Research. ,vol. 85, pp. 211- 222 ,(2005) , 10.1017/S0016672305007603