Comparative Chromosome Mapping: Rodent Models


A comparative chromosome map of two species describes the groups of genes and chromosome segments that have maintained physical proximity to each other on a chromosome since the species diverged and throughout subsequent evolution. Usually a comparative map describes the chromosomal homologies between two species using one species as a reference organism for one or more others.

Keywords: gene mapping; high‐resolution cytogenetics; linkage groups; rodent models; Zoo‐FISH

Figure 1.

Phylogenetic tree of primates, ungulates and rodents. The phylogenetic relationships among primates, ungulates and rodents are shown schematically. The lineage separating humans and rodents separated 60–100 million years ago (mya). Since that branchpoint, the ungulates have diverged from the line that has given rise to the primates. Among the rodents, the mouse and rat diverged 25–38 mya, and within the mouse lineage Mus musculus and Peromyscus maniculatus diverged 17 mya. (Note that the lineages are not drawn to scale.)

Figure 2.

Genetic recombination. (a) A pair of premeiotic chromosomes, or homologs, is represented with alleles A–B–C–D–E–F–G–H–I on the left homolog and alleles a–b–c–d–e–f–g–h–i on the right homolog. The X, giving rise in (b) to the recombinant chromosomes with alleles A–B–C–d–e–f–g–h–i and alleles A–B–C–d–e–f–g–h–i indicates a recombination event between genes (C/c) and (D/d). (c) With completion of meiosis, the homologs shown in (b) will separate, duplicate and appear in individual offspring. In the example shown, the recombination event is illustrated as it might occur in a single animal, but the recombination could occur at any point along the chromosome. In a large series of animals, the offspring would carry a variety of recombinant chromosomes. The alleles that would most frequently be recombined are those that are most distant from each other (i.e. the A and I alleles) and those that would most infrequently be recombined are the adjacent pairs (e.g. A and B or B and C, etc.).

Figure 3.

High‐resolution comparative mapping. Human (HSA), chimpanzee (PTR), gorilla (GGO), orangutan (PPY), African green monkey (CAE), cat (FCA) and mouse (MMU) chromosomes are arranged to demonstrate homologous segments by high‐resolution banding. The dotted box contains chromosome segments similar in gene content and gene order. Human chromosome 1 shows striking homology with the chromosomes of all of these mammals in this region. The genes for phosphoglucomutase‐1 (PGM‐1) and phosphogluconate dehydrogenase (PDG) have been assigned to either end of the conserved linkage in the homologous region. Mouse chromosome 4 has been inverted relative to the centromere to show the same syntenic relationship. (Reprinted from Hozier J and Davis L Analytical Biochemistry200: 205–217.)

Figure 4.

fluorescence in situ hybridization (FISH). Schematic diagram of the FISH process for cytogenetic mapping of DNA probes. (a) Probe DNA is synthesized using biotin, a chemically modified nucleotide precursor that forms the basis of the fluoresence detection. Both probe DNA and chromosomal DNA are denatured (b) and allowed to hybridize under high‐stringency reannealing conditions (c). The fluorescence signal is produced with fluorescently conjugated (fluorescein isothiocyanate, FITC) avidin (which has affinity for the biotin in the modified nucleotide precursor). The fluorescence signal on the chromosome is viewed microscopically. (Reprinted from Hozier J and Davis L Analytical Biochemistry200: 205–217.)

Figure 5.

Zoo‐FISH: Mus musculus and Rattus norvegicus. Individual M. musculus whole‐chromosome painting probes were labeled with fluorescent tags and hybridized to R. norvegicus chromosomes. (a) M. musculus chromosome 11 probe on M. musculus metaphase chromosome 11. (b) M. musculus chromosome 1 probe hybridized to R. norvegicus chromosomes 9 (large arrows) and 13 (small arrows). (c) Post‐FISH Giemsa‐stained image of the R. norvegicus metaphase shown in (b). (d) M. musculus chromosome 4 hybridized to R. norvegicus chromosome 5. (e) M. musculus chromosome 11 probe on R. norvegicus chromosomes 10 (large arrows) and 14 (small arrows). (f) M. musculus chromosome 7 probe on R. norvegicus chromosome 1. (g) M. musculus chromosome 19 probe on a different (more distal) segment of R. norvegicus chromosome 1. (h) M. musculus X probe on the R. norvegicus X chromosome. (Reprinted from Scalzi JM and Hozier JC Genomics47: 44–51.)

Figure 6.

Partial comparative map of Mus musculus and Rattus norvegicus. The data in Figure is shown here schematically. The individual rat ideograms are labeled below each chromosome, and the individual mouse (M) probes are labeled on the right of each ideogram. (Reprinted from Scalzi JM and Hozier JC Genomics47: 44–51.)

Figure 7.

Subchromosomal probes for Mus musculus chromosome 11. (a) Five M. musculus subchromosome segments were prepared by microdissecting M. musculus chromosome 11, beginning from the centromere, into five segments. (The remainder of the chromosome after each dissection is shown.) Each subchromosome segment was labeled and hybridized individually to M. musculus chromosome 11. (b) Bands A2–5. (c) Band B1. (d) Bands B2–3. (e) Bands C and D. (f) Band E. (g) Ideogram for mouse chromosome 11 with each dissection shown on the right in brackets. Band A1, the centromere, was discarded.

Figure 8.

Subchromosomal homology between Mus musculus chromosome 11 and Rattus norvegicus chromosome 10. The mouse chromosome 11 subchromosome bands shown in Figure were labeled and hybridized to R. norvegicus chromosomes. (a) M. musculus bands A2–5 hybridized to R. norvegicus chromosome 10 (large arrows) and the distal band of R. norvegicus chromosome 14 (small arrows). (b) M. musculus band B1. (c) M. musculus bands B2–3. (d) M. musculus bands C and D. (e) M. musculus band E. Note that the individual bands hybridize to R. norvegicus chromosome 10 in the same order as M. musculus chromosome 11, with the exception that the most proximal band also hybridizes to the distal end of R. norvegicus chromosome 14, indicating a single evolutionary translocation between R. norvegicus chromosome 10 and M. musculus chromosome 11.


Further Reading

Anderrsson A, Archibald A, Ashburner M, et al. (1996) Comparative genome organization of vertebrates. Mammalian Genome 7: 717–734.

Copeland N, Jenkins N, Gilbert D, et al. (1993) A genetic linkage map of the mouse: current applications and future prospects. Science 262: 57–66.

Erickson R (1989) Why isn't a mouse more like a man? Trends in Genetics 5: 1–2.

Holmquist G (1989) Evolution of chromosome bands: molecular ecology of noncoding DNA. Journal of Molecular Evolution 28: 469–486.

Hozier J and Davis L (1992) Cytogenetic approaches to genome mapping. Analytical Biochemistry 200: 205–217.

Jacob H, Brown D, Bunker R, et al. (1995) A genetic linkage map of the laboratory rat Rattus norvegicus. Nature Genetics 9: 63–69.

Liechty M, Hall B, Scalzi J, et al. (1995) Mouse chromosome‐specific painting probes generated from microdissected chromosome. Mammalian Genome 6: 592–594.

Reid T, Arnold N, Ward D and Weinberg J (1993) Comparative high resolution mapping of human and primate chromosomes by fluorescence in‐situ hybridization. Genomics 18: 381–386.

Sawyer J and Hozier J (1986) High resolution of mouse chromosomes: banding conservation between man and mouse. Science 232: 1632–1635.

Scalzi JM and Hozier JC (1998) Comparative genome mapping: mouse and rat homologies revealed by fluorescence in situ hybridization. Genomics 47: 44–51.

Scherthan H, Cremer T, Arnason U, et al. (1994) Comparative chromosome painting discloses homologous segments in distantly related mammals. Nature Genetics 6: 342–347.

Searle A, Peters J, Lyon M, et al. (1989) Chromosome maps of mouse and man. Annals of Human Genetics 53: 89–140.

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Davis, Lisa M, Liechty, Melissa C, and Hozier, John C(Sep 2006) Comparative Chromosome Mapping: Rodent Models. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005804]