Journal home
Advance online publication
Current issue
Archive
Press releases
Free Association (blog)
Supplements
Focuses
Guide to authors
Online submissionOnline submission
For referees
Free online issue
Contact the journal
Subscribe
Advertising
work@npg
Reprints and permissions
About this site
For librarians
 
NPG Resources
Nature
Nature Biotechnology
Nature Cell Biology
Nature Medicine
Nature Methods
Nature Reviews Cancer
Nature Reviews Genetics
Nature Reviews Molecular Cell Biology
news@nature.com
Nature Conferences
NPG Subject areas
Biotechnology
Cancer
Chemistry
Clinical Medicine
Dentistry
Development
Drug Discovery
Earth Sciences
Evolution & Ecology
Genetics
Immunology
Materials Science
Medical Research
Microbiology
Molecular Cell Biology
Neuroscience
Pharmacology
Physics
Browse all publications
Article
Nature Genetics  7, 472 - 479 (1994)
doi:10.1038/ng0894-472

A physical map and candidate genes in the BRCA1 region on chromosome 17q12−21

H.M. Albertsen1, 5, S. A. Smith1, S. Mazoyer2, E. Fujimoto1, J. Stevens1, B. Williams1, P. Rodriguez1, C. S. Cropp3, P. Slijepcevic2, M. Carlson1, M. Robertson1, P. Bradley1, E. Lawrence1, T. Harrington2, Z. Mei Sheng3, R. Hoopes4, N. Sternberg4, A. Brothman1, R. Callahan3, B. A. J. Ponder2 & Ray White1

  1Eccles Institute of Human Genetics and Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84112, USA

  2CRC Human Cancer Genetics Research Group, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB21QP, UK

  3Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA

  4The Du Pont Merck, Pharmaceutical Company, Wilmington, Delaware 19880-0328, USA

  5Correspondence should be addressed to H.M.A.

We have constructed a physical map of a 4 cM region on chromosome 17q12−21 that contains the hereditary breast and ovarian cancer gene BRCA1. The map comprises a contig of 137 overlapping yeast artificial chromosomes and P1 clones, onto which we have placed 112 PCR markers. We have localized more than 20 genes on this map, ten of which had not been mapped to the region previously, and have isolated 30 cDNA clones representing partial sequences of as yet unidentified genes. Two genes that lie within a narrow region defined by meiotic breakpoints in BRCA1 patients have been sequenced in breast cancer patients without revealing any deleterious mutations. These new reagents should facilitate the identification of BRCA1.

REFERENCES
  1. Hall, J.M. et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250, 1684−1689 (1990). | PubMed  | ISI | ChemPort |
  2. Easton, D.F. et al. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am. J. hum. Genet. 52, 678−701 (1993). | PubMed  | ISI | ChemPort |
  3. Bowcock, A.M. et al. THRA1 and D17S183 flank an interval of <4 cM for the breast-ovarian cancer gene (BRCA1) on chromosome b17q21. Am. J. hum. Genet. 52, 718−722 (1993). | PubMed  | ISI | ChemPort |
  4. Chamberlain, J.S. et al. BRCA1 maps proximal to D17S579 on chromosome 17q21 by genetic analysis. Am. J. hum. Genet. 52, 792−798 (1993). | PubMed  | ISI | ChemPort |
  5. Anderson, L.A. et al. High-density genetic map of the BRCA1 region of Chromosome-17q12−q21. Genomics 17, 618−623 (1993). | Article | PubMed  | ISI | ChemPort |
  6. Albertsen, H. et al. Genetic mapping of the BRCA1 region on chromosome 17q21. Am. J. hum. Genet. 54, 516−525 (1994). | PubMed  | ISI | ChemPort |
  7. Abel, K.J. et al. A radiation hybrid map of the BRCA1 region of chromosome-17q12−q21. Genomics 17, 632−641 (1993). | Article | PubMed  | ISI | ChemPort |
  8. O'Connell, P. et al. A radiation hybrid map of the BRCA1 region. Am. J. hum. Genet. 54, 526−534 (1994). | PubMed  | ChemPort |
  9. Flejter, W.L. et al. Multicolor FISH mapping with Alu-PCR-amplifled YAC clone DMA determines the order of markers in the BRCA1 region on chromosome 17q12−q21. Genomics 17, 624−631 (1993). | Article | PubMed  | ISI | ChemPort |
  10. Albertsen, H.M. et al. Construction and characterization of a human yeast artificial chromosome library containing seven haploid genome equivalents. Proc. natn. Acad. Sci. U.S.A. 87, 4256−4260 (1990). | ChemPort |
  11. Chumakov, I.M. et al. Isolation of chromosome 21-specific yeast artificial chromosomes from a total human genome library. Nature Genet. 1, 222−225 (1992). | Article | PubMed  | ISI | ChemPort |
  12. Anand, R., Riley, J.H., Smith, J.C. & Markham, A.F. A 3.5 genome equivalent multi access YAC library: construction, characterisation, screening and storage. Nucl. Adds Res. 18, 1951−1955 (1990). | ChemPort |
  13. Burke, D.T., Carle, G.F. & Olson, M.V. Cioning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science 236, 806−812 (1987). | PubMed  | ISI | ChemPort |
  14. Shepherd, N.S. et al. Preparation and screening of an arrayed human genomic library generated with the P1 cloning system. Proc. natn. Acad. Sci. U.S.A. 91, 2629−2633 (1994). | ChemPort |
  15. Xu, W., Rider, S.H., Tanner, M. & Solomon, E. Mapping of human chromosome 17 using a combination of pulsed field gel electrophoresis and chromosome mediated gene transfer. Cytogenet. Cell Genet. 51, 1111−1112 (1989). | ISI |
  16. Lemons, R.S. et al. Cloning and characterization of the t(15;17) translocation breakpoint region in acute promyelocytic leukemia. Genes Chrom. Cancer 2, 79−87 (1990). | PubMed  | ISI | ChemPort |
  17. Simard, J. et al. Genetic mapping of the breast-ovarian cancer syndrome to a small Interval on chromosome 17q12−21: exclusion of candidate genes EDH17B2 and RARA. Hum. molec. Genet. 2, 1193−1199 (1993). | PubMed  | ISI | ChemPort |
  18. Goldgar, D.E. et al. A large kindred with 17q-linked breast and ovarian cancer, genetic, phenotypic, and genealogical analysis. J. natn. Cancer Inst. 86, 200−209 (1994). | ChemPort |
  19. Campbell, I.G. et al. A novel gene encoding a B-box protein within the BRCA1 region at 17q21.1. Hum. molec. Genet. 3, 589−594 (1994). | PubMed  | ISI | ChemPort |
  20. Chavrier, P., Parton, R.G., Hauri, H.P., Simons, K. & Zerial, M. Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments. Cell 62, 317−329 (1990). | Article | PubMed  | ISI | ChemPort |
  21. Nikaido, T. et al. Cloning and nucleotide sequence of cDNA for Ki antigen, a highly conserved nuclear protein detected with sera from patients with systemic lupus erythematosus. Clin. exp. Immunol. 79, 209−214 (1990). | PubMed  | ISI | ChemPort |
  22. Georgakopoulos, T. & Thireos, G. Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription. EMBO J. 11, 4145−4152 (1992). | PubMed  | ISI | ChemPort |
  23. Sprinkle, T.J., Kouri, R.E., Fain, P.D., Stoming, T.A. & Whitney, J.B. Chromosomal mapping of the human CNP gene using a meiotic crossover DNA panel, PCR, and allele-specific probes. Genomics 16, 542−5 (1993). | Article | PubMed  | ISI | ChemPort |
  24. Tonin, P. et al. The human Insulin-like growth factor-binding protein 4 gene maps to chromosome region 17q12−q21.1 and is close to the gene for hereditary breast/ovarian cancer. Genomics 18, 414−417 (1993). | Article | PubMed  | ISI | ChemPort |
  25. Tsai-Pflugfelder, M. et al. Cloning and sequencing of cDNA encoding human DNA topolsomerase II and localization of the gene to chromosome region 17q21−22. Proc. natn. Acad. Sci. U.S.A. 85, 7177−7181 (1988). | ChemPort |
  26. Elshoubagy, N. et al. Cloning and expression of a human ATP-citrate lyase cDNA. Eur. J. Biochem. 204, 491−499 (1992). | PubMed  |
  27. Kohri, K. et al. Cloning and structural determination of human peptide YY cDNA and gene. Biochem. Blophys. Acta 1173, 345−349 (1993). | Article | ChemPort |
  28. Kelsell, D.P., Black, D.M., Bishop, D.T. & Spurr, N.K. Genetic analysis of the BRCA1 region in a large breast/ovarian family: refinement of the minimal region containing BRCA1. Hum. molec. Genet. 2, 1823−1828 (1993). | PubMed  | ISI | ChemPort |
  29. Smith, S.A. et al. Localization of the breast-ovarian cancer susceptibility gene (BRCA1) on 17q12−21 to an interval of 1 cM. Genes Chrom. Cancer. 10, 71−76 (1994). | PubMed  | ISI | ChemPort |
  30. Smith, S.A., Easton, D.F., Evans, D.G.R. & Ponder, B.A.J. Allele losses in the region 17q12−21 in familial breast and ovarian cancer involve the wild-type chromosome. Nature Genet. 2, 128−131 (1992). | Article | PubMed  | ISI | ChemPort |
  31. Cropp, C.S. et al. Evidence for involvement of BRCA1 in sporadic breast carcinomas. Cancer Res. 54, 2548−2551 (1994). | PubMed  | ISI | ChemPort |
  32. Green, E.D. & Olson, M.V. Systematic screening of yeast artificial-chromosome libraries by use of the polymerase chain reaction. Proc. natn. Acad. Sci. U.S.A. 87, 1213−1217 (1990). | ChemPort |
  33. Riley, J. et al. A novel, rapid method for the isolation of terminal sequences from yeast artificial chromosome (YAC) clones. Nucl. Acids Res. 18, 2887−2890 (1990). | PubMed  | ISI | ChemPort |
  34. Trask, B.J., Massa, H., Kenwick, S. & Gitschier, J. Mapping of human chromosome Xq28 by two-color fluorescence in situ hybridization of DNA sequences to interphase cell nuclei. Am. J. hum. Genet. 48, 1−15 (1991). | PubMed  | ISI | ChemPort |
  35. Feinberg, A.P. & Vogelstein, B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132, 6−13 (1984). | ISI |
  36. Joslyn, G. et al. Identification of deletion mutations and three new genes at the familial polyposls locus. Cell 66, 601−613 (1991). | Article | PubMed  | ISI | ChemPort |
  37. Nelson, D.L. et al. Alu polymerase chain reaction: a method for rapid isolation of human-specific sequences from complex DNA sources. Proc. natn. Acad. Sci. U.S.A. 88, 6686−6690 (1989).
  38. Tagle, D.A. & Collins, F.S. An optimized Alu-PCR primer pair for human-specific amplification of YACs and somatic cell hybrids. Hum. molec. Genet. 1, 121−122 (1992). | PubMed  | ChemPort |
  39. Altschul, S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. Basic local alignment search tool. J. molec. Biol. 215, 403−410 (1990). | Article | PubMed  | ISI | ChemPort |
  40. Emi, M. et al. A novel metalloprotease/dysintegerin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers. Nature Genet. 5, 151−157 (1993). | Article | PubMed  | ISI | ChemPort |
 Top
 Top
Abstract
Previous | Next
Table of contents
Download PDFDownload PDF
Send to a friendSend to a friend
Save this linkSave this link

naturejobs

References
Export citation
Export references
natureproducts

Search buyers guide:

 
ADVERTISEMENT
 
Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
Journal home | Advance online publication | Current issue | Archive | Press releases | Supplements | Focuses | For authors | Online submission | Permissions | For referees | Free online issue | About the journal | Contact the journal | Subscribe | Advertising | work@npg | naturereprints | About this site | For librarians
Nature Publishing Group, publisher of Nature, and other science journals and reference works©1994 Nature Publishing Group | Privacy policy