Cytogenet Genome Res 96:52–59 (2002) Evolutionary aspects of the genomic organization of rat chromosome 10 A. Behboudi, a E. Sjöstrand, a P. Go ´mez-Fabre, a Å. Sjöling, a Z. Taib, b K. Klinga-Levan, a F. Ståhl a and G. Levan a a Department of Cell and Molecular Biology – Genetics, Lundberg Laboratory, Göteborg University, Göteborg, and b Department of Mathematics, Chalmers University of Technology, Göteborg (Sweden) This article is dedicated to Professor Karl Fredga to commemorate his retirement and lifelong cytogenetic research activities. Supported by grants from the Swedish Medical Research Council, the Swedish Natu- ral Science Research Council, SWEGENE, the Erik Philip-Sörensen Foundation, the Carl Trygger Foundation, the Nilsson-Ehle Foundation, and the IngaBritt and Arne Lundberg Research Foundation. Received 12 February 2002; manuscript accepted 22 May 2002. Request reprints from G. Levan, CMB-Genetics, Box 462 SE 405 30 Göteborg, (Sweden); telephone: +46-31 773 3290 fax: +46-31 773 2599; e-mail: Goran.Levan@gen.gu.se Data deposition: DNA sequence from the rat gene E4f1 has been submitted to Gen- Bank and was assigned Accession No. AY78091. ABC Fax + 41 61 306 12 34 E-mail karger@karger.ch www.karger.com © 2002 S. Karger AG, Basel 0301–0171/02/0964–0052$18.50/0 Accessible online at: www.karger.com/journals/cgr Abstract. Using FISH and RH mapping a chromosomal map of rat chromosome 10 (RNO10) was constructed. Our mapping data were complemented by other published data and the final map was compared to maps of mouse and human chromosomes. RNO10 contained segments homologous to mouse chromosomes (MMU) 11, 16 and 17, with evolutionary breakpoints between the three segments situated in the proxi- mal part of RNO10. Near one of these breakpoints (between MMU17 and 11) we found evidence for an inversion ancestral to the mouse that was not ancestral to the condition in the rat. Within each of the chromosome segments identified, the gene order appeared to be largely conserved. This conservation was particularly clear in the long MMU11-homologous segment. RNO10 also contained segments homologous to three human chromosomes (HSA5, 16, 17). However, within each segment of conserved synteny were signs of more extensive rearrange- ments. At least 13 different evolutionary breakpoints were indi- cated in the rat-human comparison. In contrast to what was found between rat and mouse, the rat-human evolutionary breaks were distributed along the entire length of RNO10. Copyright © 2002 S. Karger AG, Basel Recent developments have led to much progress in the genome mapping of several mammalian species including hu- mans, rodents and domestic animals. Genomic cross-species comparative mapping and sequencing of vertebrates can be powerful methods in providing insight into evolutionary ge- nome rearrangements as well as in paving the way for function- al analysis and interpretation of the human genomic sequence data (Miller, 2000; Summers et al., 2001). Furthermore, the refinement of comparative maps across mammalian genomes will specify where chromosome breakage and rearrangements have taken place between species (Summers et al., 2001), and will provide the basis for exchanging genetic data between dif- ferent mammalian species, including humans (Go ´ mez-Fabre et al., 2002). Such data exchange will lead to rapid development of the gene maps in map-poor species, and can be extended to reveal historical karyotype events, permitting the visualization of the organization of chromosome complements in extinct ancestors to present-day species. Refined methodology, partic- ularly in fluorescence in situ hybridization (FISH) and radia- tion hybrid (RH) mapping has led to significant improvements in the resolution of the rat genome physical map. These devel- opments have extended the use of the laboratory rat as an effi- cient tool for the study of the genetic basis of complex diseases (Jacob and Kwitek, 2002). Presently, projects to sequence the rat genome are under way and the prognosis is that draft sequence covering the entire genome will be available in the spring of 2003 (http://www.hgsc.bcm.tmc.edu/projects/rat/). Obviously, the assembly of the sequence information can be greatly facilitated if accurate and detailed chromosome maps are prepared in advance. Our earlier work has shown that rat chromosome 10 (RNO10) contains segments homologous to three different human chromosomes (HSA5, 16, 17) and to three mouse chromosomes (MMU11, 16, 17) (Nilsson et al.,