Small RNA sequencing on liver samples of DO mice

Genetic variation, in addition to environmental influences like diet, can govern the expression levels of microRNAs (miRNAs). MiRNAs are commonly found to operate cooperatively in groups to regulate gene expression. To investigate this, we combined small RNA sequencing, clinical phenotypes, and microarray data measuring gene expression from an outbred mouse model, the Diversity Outbred population. In the DO population, each individual has a distinct genome that is a mosaic of 8 inbred founder strains. We used these data to identify co-regulated modules of miRNAs and genes that are influenced by genetics and diet, and identify relationships between the modules and phenotypes in over 200 DO mice. Investigation of differences in microRNA expression in DO mice fed either a high-fat, high-cholesterol diet with added cholic acid (HFCA), or a calorie-match high protein (HP) diet used as a control, for 18 weeks. One of each sibling pair was placed on either diet