The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
These results provide both novel information about genome regions in humans that influence interindividual blood pressure variation and a basis for identifying the contributing genes. Identification of the functional mutations in these genes may uncover novel mechanisms for blood pressure regulation and suggest new therapies and prevention strategies.
The Family Blood Pressure Program (FBPP) consists of 4 independently established multicenter networks of investigators who have complementary approaches to the genetics of blood pressure levels and hypertension. The program has recruited participants from the African American, Mexican American, Asian, and non-Hispanic white populations. Each network utilized study designs, laboratory measurements, and analytic methods that made efficient use of the unique characteristics of their populations and the investigators' expertise. The individual networks subsequently unified core study components into a single cohesive program. The unified FBPP includes (1) standardized clinic and laboratory protocols for core variables to facilitate direct comparison of results among networks, (2) coordination among laboratories to avoid unnecessary duplication of effort, (3) utilization of a single laboratory for genome-wide marker typing, and (4) a pooled data set containing phenotype and genotype information from >11 000 individuals.
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