Detailed chromosomal and radiation hybrid mapping in the proximal part of rat Chromosome 10 and gene order comparison with mouse and human

Abstract

The rat provides valuable and sometimes unique models of human complex diseases. To fully exploit the rat models in biomedical research, it is important to have access to detailed knowledge of the rat genome organization as well as its relation to the human genome. Rat Chromosome 10 (RNO10) harbors several important cancer-related genes. Deletions in the proximal part of RNO10 were repeatedly found in a rat model for endometrial cancer. To identify functional and positional candidate genes in the affected region, we used radiation hybrid (RH) mapping and single- and dual-color fluorescence in situ hybridization (FISH) techniques to construct a detailed chromosomal map of the proximal part of RNO10. The regional localization of 14 genes, most of them cancer-related ( Grin2a, Gspt1, Crebbp, Gfer, Tsc2, Tpsb1, Il9r, Il4, Irf1, Csf2, Sparc, Tp53, Thra1, Gh1), and of five microsatellite markers ( D10Mit10, D10Rat42, D10Rat50, D10Rat72, and D10Rat165) was determined on RNO10. For a fifteenth gene, Ppm1b, which had previously been assigned to RNO10, the map position was corrected to RNO6q12-q13.

Evolutionary aspects of the genomic organization of rat chromosome 10

“…However, the evolutionary breakpoints are mostly different, suggesting that they represent independent events. From our previous study it appeared that in the most proximal part of RNO10 (covering bands q11 → q12), the conserved homology was greater when rats were compared to humans than when they were compared to mice, in spite of the much greater evolutionary distance (Behboudi et al, 2002a). This was because the entire region was found at a single location in humans (at HSA16p13), whereas it was subdivided onto two different chromosomes (MMU16 and 17) in the mouse.…”

“…Available DNA sequences for the rat, mouse and human homologs were collected from GenBank and 1-3 primer pairs were designed for each gene using Primer3 (http://www-genome.wi.mit.edu/cgi-bin/primer/primer3_www. cgi) and PCR was performed as described previously (Behboudi et al, 2002a).…”

“…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, 2001;Behboudi et al, 2002a). However, the evolutionary breakpoints are mostly different, suggesting that they represent independent events.…”

Integrative Genomics: In Silico Coupling of Rat Physiology and Complex Traits With Mouse and Human Data

“…With each development, much effort has been expended to integrate and reference the resulting maps: genetic (Brown et al 1998;Remmers et al 1999;Dracheva et al 2000); genetic with RH (Steen et al 1999;Bihoreau et al 2001); and cytogenetic, genetic, and RH (Szpirer et al 1997(Szpirer et al , 1998(Szpirer et al , 1999Kitada et al 2000;Behboudi et al 2002). Comparative integration between human and mouse maps has been similarly popular (examples include Marino et al 1986;Szpirer et al 1990Szpirer et al , 2000Yamada et al 1994;Kuroiwa et al 1998;Serikawa et al 1998;Hornum and Markholst 2000;Kaisaki et al 2000;Kwitek et al 2001;Nilsson et al 2001).…”

“…The power of RH mapping is the ability to map anything for which a unique set of primers can be designed and specifically amplified in rat. This approach removes the requirement for "polymorphism" and results in numerous genes and sequences being mapped onto the genome (see al-Majali et al 1999;Gosele et al 2000;Schulz et al 2000;Avner et al 2001;Laes et al 2001;Szpirer et al 2001;Tseng et al 2001Tseng et al , 2002Behboudi et al 2002;Dobbins et al 2002;Wallace et al 2002). Online map servers (Rat Radiation Hybrid Mapserver; http://ratmap.ims.u-tokyo.ac.jp/ cgi-bin/RH/rhNgv.pl), which take PCR results as input and return a map location referenced to a common framework map, have removed the need for laboratories to undertake their own largescale mapping projects.…”