Document Detail

A 350-kb cosmid contig in 3p14.2 that crosses the t(3;8) hereditary renal cell carcinoma translocation breakpoint and 17 aphidicolin-induced FRA3B breakpoints.
MedLine Citation:
PMID:  8661108     Owner:  NLM     Status:  MEDLINE    
The constitutive fragile site at human chromosomal band 3p14.2, FRA3B, has been described as the most active common fragile site in the human genome. FRA3B is cytologically indistinguishable from the chromosome 3 breakpoint observed in the hereditary renal cell carcinoma (hRCC) translocation t(3;8) (p14.2;q24.13). Previous work demonstrated that a 1330-kb YAC clone, YC850A6, spans both the t(3;8) translocation and FRA3B and also encompasses FRA3B-associated breakpoints induced in hamster-human hybrids. This YAC was used to construct a multi-hit cosmid library. Screening of this library resulted in a 350-kb cosmid contig that extends distally from the t(3;8) translocation breakpoint. Seventeen aphidicolin-induced 3p14. 2 breakpoints derived from hamster-human hybrids were mapped within this cosmid contig. These breakpoints were found to localize as two distinct clusters, separated by 200 kb, which lie on either side of a region of frequent breakage within FRA3B as defined by FISH analysis using cosmids from the contigs. The most proximal of the breakpoint clusters lies approximately 100 kb distal to the hRCC t(3;8) breakpoint. The distribution of these breakpoints, together with the region of frequent chromosomal breakage mapped by FISH analysis, further confirms the position of FRA3B and helps to define the extent over which its fragility is exerted. These data indicate that FRA3B comprises several hundred kilobases of DNA sequence within 3p14.2. The 350-kb contig and the cosmid library constructed from YAC YC850A6 will be essential for further characterization of the region surrounding FRA3B and in experiments to determine the molecular basis of the fragility of FRA3B.
W Paradee; C M Wilke; L Wang; R Shridhar; C M Mullins; A Hoge; T W Glover; D I Smith
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Genomics     Volume:  35     ISSN:  0888-7543     ISO Abbreviation:  Genomics     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1996-09-30     Completed Date:  1996-09-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8800135     Medline TA:  Genomics     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  87-93     Citation Subset:  IM    
Department of Molecular Biology and Genetics, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/U47015;  U47016
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MeSH Terms
Aphidicolin / pharmacology*
Base Sequence
Carcinoma, Renal Cell / genetics*
Chromosome Fragile Sites
Chromosome Fragility*
Chromosomes, Artificial, Yeast / genetics
Chromosomes, Human, Pair 3 / drug effects,  genetics*,  ultrastructure
Chromosomes, Human, Pair 8 / ultrastructure*
Cosmids / genetics*
DNA-Directed DNA Polymerase / antagonists & inhibitors
Enzyme Inhibitors / pharmacology*
Gene Library
Hybrid Cells
Kidney Neoplasms / genetics*
Molecular Sequence Data
Neoplastic Syndromes, Hereditary / genetics*
Polymerase Chain Reaction
Translocation, Genetic*
Trinucleotide Repeats
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 38966-21-1/Aphidicolin; EC DNA Polymerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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