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Published August 15, 1996 | public
Journal Article

Generation of an Integrated Transcription Map of the BRCA2 Region on Chromosome 13q12–q13

Abstract

An integrated approach involving physical mapping, identification of transcribed sequences, and computational analysis of genomic sequence was used to generate a detailed transcription map of the 1.0-Mb region containing the breast cancer susceptibility locus BRCA2 on chromosome 13q12–q13. This region is included in the genetic interval bounded by D13S1444 and D13S310.Retrieved sequences from exon amplification or hybrid selection procedures were grouped into physical intervals and subsequently grouped into transcription units by clone overlap. Overlap was established by direct hybridization, cDNA library screening, PCR cDNA linking (island hopping), and/or sequence alignment. Extensive genomic sequencing was performed in an effort to understand transcription unit organization. In total, approximately 500 kb of genomic sequence was completed. The transcription units were further characterized by hybridization to RNA from a series of human tissues. Evidence for seven genes, two putative pseudogenes, and nine additional putative transcription units was obtained. One of the transcription units was recently identified as BRCA2 but all others are novel genes of unknown function as only limited alignment to sequences in public databases was observed. One large gene with a transcript size of 10.7 kb showed significant similarity to a gene predicted by the Caenorhabditis elegans genome and the Saccharomyces cerevisiae genome sequencing efforts, while another contained a motif sequence similar to the human 2′, 3′ cyclic nucleotide 3′ phosphodiesterase gene. Several retrieved transcribed sequences were not aligned into transcription units because no corresponding cDNAs were obtained when screening libraries or because of a lack of definitive evidence for splicing signals or putative coding sequence based on computational analysis. However, the presence of additional genes in the BRCA2 interval is suggested as groups of putative exons and hybrid selected clones that were transcribed in consistent orientations could be localized to common physical intervals.

Additional Information

© 1996 by Academic Press, Inc. Received March 22, 1996; accepted May 29, 1996. B.L.W. is supported by NIH Grants CA57601 and CA61231. F.J.C. is supported by NIH grant CA67403. J.M.R. and J.S. are Scholars of the Medical Research Council (MRC) of Canada while F. L. is a MRC Career Scientist. J.S. and F.L. are supported by MRC and Endorecherche Inc. S.N., M.H.S., and D.E.G. are supported by U.S. Army Grant DAMD17-94-J-4260 and NIH Grants CA55914, CA48711, CA65673, RR00064, CN05222, and CA42014. J.M.R. is member of the Canadian Genetic Diseases Network.

Additional details

Created:
August 19, 2023
Modified:
October 26, 2023