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A comparative mapping study of fragile sites in the human and murine genomes
M Djalali1, S Adolph, P Steinbach
1Abteilung Klinische Genetik der Universität Ulm, Federal Republic of Germany.
Abstract:
Fragile sites on murine chromosomes were induced by the antimetabolites methotrexate (MTX), fluorodeoxyuridine (FdU), and aphidicolin (APD). To facilitate chromosome identification the analysis was performed on chromosomes of a CD/CD mouse that possesses nine pairs of Robertsonian translocation chromosomes of known arm composition. The pattern of induced fragile sites was rather similar for the different antimetabolites used. Many of them, e.g., 2B, 3B, 5B and 9D, are included in Giemsa-negative bands. On the X chromosome a fragile site was mapped to the region XC/D. Comparative mapping data with human fragile sites have been informative in most instances. Conservation of synteny within known linkage groups seems very likely.
Insights
Researchers induced fragile sites on mouse chromosomes using antimetabolites like methotrexate (MTX). The study found conserved fragile site patterns across different chemicals and species, aiding in comparative gene mapping.
Area of Science:
- Genetics
- Cytogenetics
- Genomic Instability
Background:
- Fragile sites are specific chromosomal regions prone to breakage.
- Understanding fragile site distribution is crucial for genetic research and disease association.
- Murine models offer valuable insights into human chromosomal phenomena.
Purpose of the Study:
- To induce and characterize fragile sites on murine chromosomes using chemical agents.
- To compare the patterns of induced fragile sites across different antimetabolites.
- To facilitate comparative mapping of fragile sites between mouse and human genomes.
Main Methods:
- Induction of fragile sites on mouse chromosomes using methotrexate (MTX), fluorodeoxyuridine (FdU), and aphidicolin (APD).
- Analysis performed on a CD/CD mouse strain with known Robertsonian translocation chromosomes for precise identification.
- Mapping of induced fragile sites, including specific locations on the X chromosome.
Main Results:
- Similar patterns of fragile sites were induced by the different antimetabolites.
- Several fragile sites were located within Giemsa-negative bands.
- A fragile site was mapped to region XC/D on the mouse X chromosome.
- Comparative analysis suggested conservation of synteny with human fragile sites.
Conclusions:
- Antimetabolites reliably induce fragile sites in murine chromosomes.
- The observed patterns indicate conserved mechanisms of fragile site induction.
- Comparative mapping of murine fragile sites aids in understanding human chromosomal abnormalities and gene linkage.