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Localization of the gene responsible for the op (osteopetrotic) defect in rats on chromosome 10
1National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Abstract:
Osteopetrosis, a skeletal disorder of inadequate bone resorption with an abnormal increase in skeletal mass, results from a variety of independent single gene mutations that affect osteoclast differentiation and/or function. The osteopetrotic defect, op, is one of four spontaneous, nonallelic mutations in rats that result in osteopetrosis. In intercross progeny of (BN/SsN x LEW/SsN. +/op) F1 carriers, we mapped this locus by linkage analysis with microsatellite markers to rat chromosome 10. The linkage group contained, as well as op, 15 anonymous DNA loci and 9 DNA loci associated with genes (interleukin-3, myosin heavy chain [skeletal, embryonic], asialoglycoprotein receptor [hepatic lectin]-1, vesicle-associated membrane protein [synaptobrevin-2], sex hormone binding globulin, aldolase C, nitric oxide synthase [inducible], erythroblastic leukemia avian viral oncogene homolog-2, and proline-rich protein). The markers for these loci include nine not previously reported. The op locus mapped to the end of the chromosome 10 linkage group, within 1 cM of the anonymous DNA locus, D10Mit6. Based on its location, the op gene is likely to be distinct from seven described mutations in mice as well as three other mutations in rats. These results may permit a positional cloning strategy to be undertaken to identify the gene and mutation underlying the op defect.
Insights
Researchers mapped the osteopetrotic defect (op) locus to rat chromosome 10 using linkage analysis. This finding aids in identifying the specific gene responsible for this skeletal disorder.
Area of Science:
- Genetics
- Molecular Biology
- Skeletal Biology
Background:
- Osteopetrosis is a skeletal disorder characterized by increased bone mass due to impaired osteoclast function.
- It arises from various single gene mutations affecting osteoclast differentiation or function.
- The osteopetrotic defect (op) is a spontaneous mutation identified in rats.
Purpose of the Study:
- To genetically map the osteopetrotic defect (op) locus in rats.
- To identify the chromosomal location of the op gene.
- To facilitate positional cloning strategies for gene identification.
Main Methods:
- Linkage analysis was performed on intercross progeny of (BN/SsN x LEW/SsN. +/op) F1 carriers.
- Microsatellite markers were utilized to map the op locus.
- The linkage group was analyzed for association with known and novel DNA loci.
Main Results:
- The op locus was successfully mapped to rat chromosome 10.
- The linkage group included 15 anonymous DNA loci and 9 loci associated with specific genes.
- The op locus is located at the distal end of chromosome 10, closely linked to the D10Mit6 marker.
Conclusions:
- The genetic location of the op locus on rat chromosome 10 has been determined.
- This mapping provides a foundation for positional cloning to identify the underlying gene and mutation.
- The op gene is likely distinct from previously identified osteopetrosis mutations in rats and mice.