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Integrative genetics and genomics study of the hypertriglyceridemia in a polygenic type 2 diabetes mouse model
Author(s) -
Kim Jung Han,
Kim Hyoung Yon,
Stewart Taryn,
Saxton Arnold
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.294.1
Subject(s) - biology , genetics , genetic association , type 2 diabetes , genome wide association study , gene , genetic variation , candidate gene , genotype , single nucleotide polymorphism , diabetes mellitus , endocrinology
Hypertriglyceridemia (HTG) is the dominant dyslipidemia in type 2 diabetes (T2D). The aim of this study was to elucidate genetic networks underlying the HTG in a polygenic model for T2D, TALLYHO/JngJ (TH) mice. We conducted a large‐scale microarray gene expression analysis using 16 F2 male mice from a (C57BL/6J x TH) F1 intercross; 8 each from the upper and lower tails for plasma triglyceride distribution of 400 F2 mice. At 24 wk, mice were killed, and liver, muscle, and pancreas were collected and the total RNA isolated and hybridized on the mouse genome 430 2.0 array (Affymetrix). Mice were also genotyped with 68 genetic markers spaced across the whole genome. Individual probe data were extracted using Bioconductor, and the gcRMA normalization was used to produce a signal measure for each gene. Statistical analysis was performed using SAS software, and a mixed ANOVA model was run on the normalized data, fitting genotype and tissue effects, and using array variation as the experimental error. Genes with significant (p<0.05) ANOVA interaction, and significant pair‐wise False Discovery Rate were considered differentially expressed, identifying 1377 in pancreas, 494 in muscle, and 1094 genes in liver. Examining differentially expressed genes using known pathway networks revealed the insulin signaling pathway as the most commonly enriched category in the three tissues tested. American Diabetes Association 7‐04‐RA‐52