SRA

We developed a method to prioritise strain-specific haplotypes by integrating genomic variation and genomic regulatory data predicted to be involved in specific phenotypes. To identify genomic regions associated with metabolic syndrome (MetS), a disorder of energy utilization and storage affecting several organ systems, we compared two Lyon rat strains, LH/Mav which is susceptible to MetS, and LL/Mav, which is susceptible to obesity as an intermediate MetS phenotype, with a third strain (LN/Mav) that is resistant to both MetS and obesity. Applying a novel metric, we ranked the identified strain-specific haplotypes using evolutionary conservation of the occupancy three liver-specific transcription factors (HNF4A, CEBPA, and FOXA1) in five rodents including rat. We generated RNA-seq expression data from liver of LL rats and from kidney of all three Lyon strains (5 biological replicates) and integrated these with relevant existing data including the level of regulatory conservation for three liver-specific transcription factors (CEBPA, FOXA1 and HNF4A between rat and five related mouse species and strains. We also used RNA-seq expression data from liver of LH and LN rats previously generated (GSE50027). Our results show that the use of functional regulatory conservation is a potentially effective approach to select strain-specific genomic regions associated with phenotypic differences among Lyon rats and could be extended to other systems.