Predictions based on the rat–mouse comparative map provide mapping information on over 6000 new rat genes

Abstract. For identification of ECS (``evolutionarily conserved segments'') between rat and mouse, 893 rat–mouse orthologous gene-pairs were brought together with zoo-FISH analysis. In total, 59 autosomal ECS and 4 X-chromosomal ones were detected. Combining FISH and zoo-FISH data, the segments were anchored on the rat chromosomes, providing an improved comparative map between the two species. Since chromosomal evolution is a slow process, it is reasonable to assume that the genome organization, including gene order, is essentially conserved within the ECS. In this way we assigned tentative subchromosomal map positions to 303 rat genes, for which no regional mapping information was available. Furthermore, the concept of prediction mapping was extended to unmapped rat homologs of genes, which in the mouse are situated inside or in the vicinity of an ECS. For a total of 6669 genes, we predicted a single rat chromosomal position, whereas for another 448 genes we could predict that they were located in one of two possible positions. Thus, our study has increased the number of genes for which there is positional mapping information in the rat almost fivefold.

[1]  S. O’Brien,et al.  Comparative genomics: lessons from cats. , 1997, Trends in genetics : TIG.

[2]  C. Webber,et al.  A radiation hybrid map of the rat genome containing 5,255 markers , 1999, Nature Genetics.

[3]  H. Himmelbauer,et al.  Comparative mapping of mouse and rat chromosomes by fluorescence in situ hybridization. , 1999, Genomics.

[4]  H. Jacob,et al.  Functional genomics and rat models. , 1999, Genome research.

[5]  J. Guénet,et al.  A comparative genetic map of rat, mouse and human genomes. , 1998, Experimental animals.

[6]  S. O’Brien,et al.  Mammalian genome organization: an evolutionary view. , 1988, Annual review of genetics.

[7]  K. Buetow,et al.  Universal mapping probes and the origin of human chromosome 3. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[8]  K. Klinga-Levan,et al.  The rat: an experimental animal in search of a genetic map. , 1996, Folia biologica.

[9]  D. Stieber,et al.  Analysis of candidate genes included in the mammary cancer susceptibility 1 (Mcs1) region , 2001, Mammalian Genome.

[10]  H. Scherthan,et al.  Emerging patterns of comparative genome organization in some mammalian species as revealed by Zoo-FISH. , 1998, Genome research.

[11]  J. Nadeau,et al.  Lengths of chromosomal segments conserved since divergence of man and mouse. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[12]  K. Helou,et al.  Amplification of Mycn, Ddx1, Rrm2, and Odc1 in rat uterine endometrial carcinomas , 2001, Genes, chromosomes & cancer.

[13]  M. Bihoreau,et al.  A high-resolution consensus linkage map of the rat, integrating radiation hybrid and genetic maps. , 2001, Genomics.

[14]  Paul Richardson,et al.  Human Chromosome 19 and Related Regions in Mouse: Conservative and Lineage-Specific Evolution , 2001, Science.

[15]  V. Sheffield,et al.  Generation of a high-density rat EST map. , 2001, Genome research.

[16]  J. Wienberg,et al.  Reciprocal chromosome painting shows that genomic rearrangement between rat and mouse proceeds ten times faster than between humans and cats , 1999, Cytogenetic and Genome Research.

[17]  N. M. Brooke,et al.  A molecular timescale for vertebrate evolution , 1998, Nature.

[18]  David Sankoff,et al.  The lengths of undiscovered conserved segments in comparative maps , 1998, Mammalian Genome.

[19]  G. J. Smith,et al.  The rat as an experimental animal. , 1989, Science.

[20]  O. Nerman,et al.  Rat-mouse and rat-human comparative maps based on gene homology and high-resolution zoo-FISH. , 2001, Genomics.

[21]  G. Levan,et al.  The gene map of the Norway rat (Rattus norvegicus) and comparative mapping with mouse and man. , 1991, Genomics.