Molecular characterization of the 3p14.2 constitutive fragile site
- Wayne State Univ. School of Medicine, Detroit, MI (United States); and others
Aphidocolin, a specific inhibitor of the alpha DNA polymerase, has been shown to induce chromosomal breakage at the common, or constitutive fragile sites. Of all the fragile sites present in the human genome, the site with the highest frequency of aphidocolin-induced breakage is within chromosomal band 3p14.2. This chromosomal region is of particular interest since it is also the site of a chromosomal translocation associated with hereditary renal cell carcinoma, the t(3;8)(p14.2;q24.1) translocation breakpoint. This band may also contain a tumor suppressor gene deleted in the formation of lung cancer and renal cell carcinoma. We previously generated a series of somatic cell hybrids from a chromosome 3-only hybrid that had a single breakpoint within 3p14.2 and had lost all distal sequences. Boldog et al. isolated a 1.3 Mb YAC clone which traversed the translocation breakpoint. We have used a lambda library constructed from this YAC to localize our breakpoints distal to the familial renal cell carcinoma translocation breakpoint. Of 13 3p14.2 aphidocolin-induced breakpoints, we have precisely located 6 within one 4.5 kb fragment. The remaining 7 appear to be clustered approximately 100 kb proximal. There are, therefore, two distinct regions distal to the familial renal cell carcinoma translocation breakpoint that contain aphidocolin-induced breakpoints clustered together. Preliminary sequence analysis of the 4.5 kb fragment have failed to identify traditional motifs (trinucleotide, etc.) to explain fragility.
- OSTI ID:
- 133736
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
CARCINOMAS
CHROMOSOMAL ABERRATIONS
DNA
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
GENES
GENETIC MAPPING
GENOME MUTATIONS
HEREDITARY DISEASES
HUMAN CHROMOSOME 3
HUMAN CHROMOSOME 8
HYBRIDIZATION
MUTATION FREQUENCY
NUCLEOTIDES
PATIENTS
POLYMERASES
SOMATIC CELLS
YEASTS