Scientists Decipher the Rat Genome
An international consortium of scientists that includes TIGR has completed a high-quality draft sequence of the rat genome. Comparing the rat to the human and mouse genomes, the Rat Genome Sequencing Project Consortium reported that nearly all human genes known to be associated with diseases have counterparts in the rat.
March 31, 2004
Rockville, MD — An international consortium of scientists, including The Institute for Genomic Research (TIGR), has completed a high-quality draft sequence of the rat genome. The project provides a valuable resource for researchers who use laboratory rats in their investigations of experimental medicines to treat human diseases.
The study — the primary results of which appear in Nature's April 1 issue — found that nearly all human genes known to be associated with diseases have counterparts in the rat genome. A few families of genes, including smell receptors and genes for dealing with toxins, have been expanded in the rat.
The Rat Genome Sequencing Project Consortium (RGSPC) was led by the Human Genome Sequencing Center at Baylor College of Medicine in Houston, in conjunction with the National Heart, Lung and Blood Institute (NHLBI) and the National Human Genome Research Institute (NHGRI) — both parts of the National Institutes of Health.
TIGR's role in the international effort — which involved more than 20 research groups in six countries — was sequencing the "BAC ends" for the rat genome. BACs (bacterial artificial chromosomes) are large fragments of an organism's DNA that can replicate inside a bacterial cell. A "BAC library" — a collection of segments of an organism's genome — can be pieced together to create a map of the whole genome.
Shaying Zhao, an assistant investigator who led the rat BAC end sequencing at TIGR, had previously conducted the Institute's BAC end sequencing of other mammals, including human, mouse and cow. She says the BAC end sequences helped scientists piece together the genome.
The high quality draft' sequence covers over 90 percent of the genome of the Brown Norway rat, Rattus norvegicus, which is widely used in laboratories for research into experimental medicine and drug development. The rat sequence is the third complete mammalian genome to be sequenced to high quality and described in a major scientific publication.
A comparison of the sequence data from rat, human, and mouse indicates that about 40 percent of the modern mammalian genome derives from the last common mammalian ancestor. The study found the rat genome — which is smaller than the human genome but slightly larger than the mouse — encodes similar numbers of genes as its human and mouse counterparts. About 30 percent of the rat genome aligns only with mouse.
A network of centers generated data and resources for the RGSP, including the BCM-HGSC, Celera Genomics, Genome Therapeutics Corporation, TIGR, British Columbia Cancer Agency Genome Sciences Centre, University of Utah, Medical College of Wisconsin, The Children's Hospital of Oakland Research Institute, and Max-Delbrí¼ck-Center for Molecular Medicine (Berlin). After the assembly of the genome at the BCM-HGSC, analysis was performed by an international team that relied largely on gene and protein predictions produced by the Ensembl project of the EMBL-EBI and Sanger Institute (UK). The project was funded mostly by the NHLBI and the NHGRI.
The combined approach to sequencing the rat genome used both whole genome shotgun (WGS) and BAC clone sequencing techniques.