Integrative analysis of hepatic transcriptional profiles reveals genetic regulation of atherosclerosis in hyperlipidemic Diversity Outbred-F1 mice.

Atherogenesis is an insipidus but precipitating process leading to serious consequences of many cardiovascular diseases (CVD). Numerous genetic loci contributing to atherosclerosis have been identified in human genome-wide association studies, but these studies have limitations in the ability to control environmental factors and to decipher cause/effect relationships. To assess the power of hyperlipidemic Diversity Outbred (DO) mice in facilitating quantitative trait loci (QTL) analysis of complex traits, we generated a high-resolution genetic panel of atherosclerosis susceptible (DO-F1) mouse cohort by crossing 200 DO females with C57BL/6J males carrying two human genes: encoding apolipoprotein E3-Leiden and cholesterol ester transfer protein.

Genetic architecture modulates diet-induced hepatic mRNA and miRNA expression profiles in Diversity Outbred mice.

Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression.

Genetic Architecture Modulates Diet-Induced Hepatic mRNA and miRNA Expression Profiles in Diversity Outbred Mice.

Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression.

Dissecting the Genetic Architecture of Cystatin C in Diversity Outbred Mice.

Plasma concentration of Cystatin C (CysC) level is a biomarker of glomerular filtration rate in the kidney. We use a Systems Genetics approach to investigate the genetic determinants of plasma CysC concentration. To do so we perform Quantitative Trait Loci (QTL) and expression QTL (eQTL) analysis of 120 Diversity Outbred (DO) female mice, 56 weeks of age.

A randomized controlled-feeding trial based on the Dietary Guidelines for Americans on cardiometabolic health indexes.

Background: The 2010 Dietary Guidelines for Americans (DGA) recommend nutrient needs be met by increasing fruit, vegetable, and whole-grain intake with the use of low-fat or fat-free dairy products and by reducing sodium, solid fats, and added sugars. However, the DGA, as a dietary pattern, have not been tested in an intervention trial.

Objective: The aim of this study was to evaluate the impact of a DGA-based diet compared with a representative typical American diet (TAD) on glucose homeostasis and fasting lipids in individuals at risk of cardiometabolic disease.