Abstract 651: Genetic Mapping Of Traits And Transcriptome In The Lyon Hypertensive Rat

Abstract

The metabolic syndrome (MetS) is characterized by obesity, dyslipidemia, hypertension, and insulin resistance and is a major risk factor for cardiovascular disease. Using the Lyon Hypertensive and Lyon Normotensive rats as models of the metabolic syndrome, we aim to determine both physiological and transcriptional regulation underlying the syndrome. To identify genetic loci influencing phenotypes underlying MetS, an F2 intercross between LH and LN with 150 offspring was studied to identify physiological quantitative trait loci (pQTL) contributing to plasma lipid levels, blood pressure, and body weight/adiposity. We performed RNA-seq in livers from 36 selected rats from the intercross to identify the mapping of gene expression, or expression (e)QTL. Linkage analyses identified pQTL and eQTL with significant logarithm of odds (lod) scores, whose genome-wide significance was determined by permutation testing. We identified 17 pQTL on 5 rat chromosomes and 75 on 16 chromosomes. It has been determined that LH chromosome 17 contributes to multiple features of MetS; furthermore, an eQTL on rat chromosome 17 was identified that regulates the expression of multiple genes in trans, meaning the regulated gene falls outside the QTL interval or on another chromosome. We hypothesize these genes share a common transcriptional regulator which is affected by genetic variation on chromosome 17. eQTLs are likely to influence precursor pathways and cofactors of the metabolic syndrome. Identifying these in the LH rat could lead to translational studies to determine their role in the human MetS.