Whole genome sequence of 27 widely studied rat models of human hypertension and diabetes.

Large numbers of inbred laboratory rat strains have been developed for a range of complex disease phenotypes. To gain insights into the evolutionary pressures underlying selection for these phenotypes, we sequenced the genomes of 27 rat strains including 11 models of hypertension, diabetes and insulin resistance, along with their respective control strains. We identified 9.6 million single nucleotide variants (SNVs), 3.5 million indels and 37,510 large deletions across these 27 rat strains. Analysis of selective sweeps and co-evolved gene clusters showed enrichment for haplotype blocks co-localising with previously mapped disease loci in rats and in human genome-wide association studies and identified known genes and new candidate genes for diabetes, hypertension and related phenotypes. These data, which we make publicly available, provide a resource for future functional and comparative genomics studies in rats and other mammals and for understanding the shared and individual mechanisms leading to complex disease phenotypes.