A. Walentinsson et al., A dual-color FISH gene map of the proximal region of rat Chromosome 4 and comparative analysis in human and mouse, MAMM GENOME, 12(12), 2001, pp. 900-908
The development and refinement of the rat genome map is a prerequisite for
a continued qualified and fruitful use of this model system for the study o
f complex traits. In two distinct rat cancer models, recurrent amplificatio
n affecting the proximal region of rat Chr 4 was detected. To further chara
cterize this region, we turned to the evolutionarily conserved chromosome s
egments in human Chr 7 and mouse Chrs 5 and 6 to identify functional and po
sitional candidate genes. By means of single- and dual-color FISH on metaph
ase,, prometaphase, and interphase chromatin, 15 genes in rat Chr 4q11-q23
(Cdk5, Hgf, Dmtf1, Abcb1, Cyp51, Cdk6, Tac1, Asns, Cav1, Met, Wnt2, Cftr, S
moh, Braf, Arhgef5) were mapped and aligned. In the course of this work, si
x cancer-related rat genes were isolated de novo and partly sequenced. Ten
loci were also mapped by FISH in the mouse. The map provides the framework
for a more detailed genetic characterization of individual tumor amplicons,
but may also be valuable for the analysis of this region in other rat mode
ls of human complex disease. In addition, our data facilitate the analysis
of events in mammalian chromosomal evolution affecting the region. In a com
parison with human sequence data, we found that there is considerable conse
rvation in this region both in gene order and in distances between genes. T
here is a single evolutionary breakpoint between rat and mouse and two betw
een rat and human. Since our analysis shows that the three breaks all occur
red in different positions, they must be independent of one another. The da
ta tend to support the notion that the genomic configuration, in rat Chr 4
is ancestral compared with that in humans and mice.